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Instructions

The bibliography lists all references used in the online course. The View by Topic selection organizes the references sequentially by Module, Lesson, and subsections in the lessons. The View by Author lists the authors in alphabetical order.

Bibliography

The bibliography lists all references used in the online course. The View by Topic selection organizes the references sequentially by Module, Lesson, and subsections in the lessons. The View by Author lists the authors in alphabetical order.

Module 2. Treatment of HBV

Lesson 1. When to Initiate HBV Treatment

Module 2 » Lesson 1. When to Initiate HBV Treatment

Background

Chang ML, Liaw YF. Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management. J Hepatol. 2014;61:1407-17.
PubMed Abstract»
Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019;23:401-16.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Walker M, El-Serag HB, Sada Y, et al. Cirrhosis is under-recognised in patients subsequently diagnosed with hepatocellular cancer. Aliment Pharmacol Ther. 2016;43:621-30.
PubMed Abstract»
Module 2 » Lesson 1. When to Initiate HBV Treatment

Goals of Therapy with Treatment of Chronic HBV

Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
PubMed Abstract»
Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol. 2011;26:628-38.
PubMed Abstract»
Chen G, Lin W, Shen F, Iloeje UH, London WT, Evans AA. Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am J Gastroenterol. 2006;101:1797-803.
PubMed Abstract»
Di Marco V, Lo Iacono O, Cammà C, et al. The long-term course of chronic hepatitis B. Hepatology. 1999;30:257-64.
PubMed Abstract»
Dienstag JL. Hepatitis B virus infection. N Engl J Med. 2008;359:1486-500.
PubMed Abstract»
Hosaka T, Suzuki F, Kobayashi M, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology. 2013;58:98-107.
PubMed Abstract»
Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678-86.
PubMed Abstract»
Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat. 2008;15:89-102.
PubMed Abstract»
Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521-31.
PubMed Abstract»
Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019;23:401-16.
PubMed Abstract»
Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: From discovery to regulatory approval. Hepatology. 2017;66:1296-1313.
PubMed Abstract»
Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-75.
PubMed Abstract»
Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med. 1996;334:1422-7.
PubMed Abstract»
Querido S, Weigert A, Adragão T, et al. Risk of hepatitis B reactivation in hepatitis B surface antigen seronegative and core antibody seropositive kidney transplant recipients. Transpl Infect Dis. 2019;21:e13009.
PubMed Abstract»
Sasadeusz J, Grigg A, Hughes PD, et al. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Other Populations and Newer Agents. Clin Liver Dis. 2019;23:521-34.
PubMed Abstract»
Sasadeusz J, Grigg A, Hughes PD, et al. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Patients with Hematological and Solid Tumor Malignancies. Clin Liver Dis. 2019;23:511-9.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Shamliyan TA, MacDonald R, Shaukat A, et al. Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference. Ann Intern Med. 2009;150:111-24.
PubMed Abstract»
Tang B, Kruger WD, Chen G, et al. Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers. J Med Virol. 2004;72:35-40.
PubMed Abstract»
Tu T, Budzinska MA, Shackel NA, Urban S. HBV DNA Integration: Molecular Mechanisms and Clinical Implications. Viruses. 2017;9.pii: E75.
PubMed Abstract»
Yao FY, Bass NM. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J Hepatol. 2000;33:301-7.
PubMed Abstract»
Module 2 » Lesson 1. When to Initiate HBV Treatment

Factors Used to Determine Whether to Initiate Treatment

Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol. 2011;26:628-38.
PubMed Abstract»
Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology. 2010;138:1747-54.
PubMed Abstract»
Choong CC, Venkatesh SK, Siew EP. Accuracy of routine clinical ultrasound for staging of liver fibrosis. J Clin Imaging Sci. 2012;2:58.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Ghany MG. Current treatment guidelines of chronic hepatitis B: The role of nucleos(t)ide analogues and peginterferon. Best Pract Res Clin Gastroenterol. 2017;31:299-309.
PubMed Abstract»
Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45:1056-75.
PubMed Abstract»
Lai M, Hyatt BJ, Nasser I, Curry M, Afdhal NH. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol. 2007;47:760-7.
PubMed Abstract»
Li Y, Huang YS, Wang ZZ, et al. Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B. Aliment Pharmacol Ther. 2016;43:458-69.
PubMed Abstract»
Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000--summary of a workshop. Gastroenterology. 2001;120:1828-53.
PubMed Abstract»
Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016;63:284-306.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
Lurie Y, Webb M, Cytter-Kuint R, Shteingart S, Lederkremer GZ. Non-invasive diagnosis of liver fibrosis and cirrhosis. World J Gastroenterol. 2015;21:11567-83.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009;49:S45-55.
PubMed Abstract»
Prati D, Taioli E, Zanella A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137:1-10.
PubMed Abstract»
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
PubMed Abstract»
Sorrell MF, Belongia EA, Costa J, et al. National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med. 2009;150:104-10.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Tseng TC, Kao JH. Treating Immune-tolerant Hepatitis B. J Viral Hepat. 2015;22:77-84.
PubMed Abstract»
World Health Organization. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. March 29, 2024.
WHO»
Module 2 » Lesson 1. When to Initiate HBV Treatment

Hepatitis B Treatment Guidance Recommendations

Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134-44.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 2 » Lesson 1. When to Initiate HBV Treatment

Special Indications for Initiating Treatment

Blackard JT, Sherman KE. Hepatitis B virus (HBV) reactivation-The potential role of direct-acting agents for hepatitis C virus (HCV). Rev Med Virol. 2018;28:e1984.
PubMed Abstract»
Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63:319-33.
PubMed Abstract»
Falade-Nwulia O, Seaberg EC, Rinaldo CR, Badri S, Witt M, Thio CL. Comparative risk of liver-related mortality from chronic hepatitis B versus chronic hepatitis C virus infection. Clin Infect Dis. 2012;55:507-13.
PubMed Abstract»
Hare CB, et al. The phase 3 Discover Study: Daily F/TAF or F/TDF for HIV Preexposure Prophylaxis. Abstract 104LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.
CROI»
Mücke MM, Backus LI, Mücke VT, et al. Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2018;3:172-180.
PubMed Abstract»
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Initiation of antiretroviral therapy. December 18, 2019.
HIV.gov»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-244.e3.
PubMed Abstract»
Sasadeusz J, Grigg A, Hughes PD, et al. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Other Populations and Newer Agents. Clin Liver Dis. 2019;23:521-34.
PubMed Abstract»
Sasadeusz J, Grigg A, Hughes PD, et al. Screening and Prophylaxis to Prevent Hepatitis B Reactivation: Patients with Hematological and Solid Tumor Malignancies. Clin Liver Dis. 2019;23:511-9.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Thio CL, Seaberg EC, Skolasky R Jr, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002;360:1921-6.
PubMed Abstract»
US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update. March 2018:1-77.
CDC»
Ahn J, Lim JK, Lee HM, et al. Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study. Am J Gastroenterol. 2016;111:1297-304.
PubMed Abstract»
Baqai S, Proudfoot J, Xu R, Kane S, Clark M, Gish R. Comparable efficacy with entecavir monotherapy and tenofovir-entecavir combination in chronic hepatitis B patients. BMJ Open Gastroenterol. 2015;2:e000030.
PubMed Abstract»
Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001-10.
PubMed Abstract»
Chang TT, Gish RG, Hadziyannis SJ, et al. A dose-ranging study of the efficacy and tolerability of entecavir in lamivudine-refractory chronic hepatitis B patients. Gastroenterology. 2005;129:1198-1209.
PubMed Abstract»
Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010;51:422-30.
PubMed Abstract»
Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886-93.
PubMed Abstract»
Cohen C, Holmberg SD, McMahon BJ, et al. Is chronic hepatitis B being undertreated in the United States? J Viral Hepat. 2011;18:377-83.
PubMed Abstract»
Colli A, Fraquelli M, Andreoletti M, Marino B, Zuccoli E, Conte D. Severe liver fibrosis or cirrhosis: accuracy of US for detection--analysis of 300 cases. Radiology. 2003;227:89-94.
PubMed Abstract»
Flemming JA, Terrault NA. Tenofovir vs Entecavir for hepatocellular carcinoma prevention in patients with chronic hepatitis B: one of these things Is not like the other. JAMA Oncol. 2019;5:17-18.
PubMed Abstract»
Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118-29.
PubMed Abstract»
Gish RG, Chang TT, Lai CL, et al. Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. J Viral Hepat. 2009;17:16-22.
PubMed Abstract»
Gish RG, Chang TT, Lai CL, et al. Quantitative hepatitis B surface antigen analysis in hepatitis B e antigen-positive nucleoside-naive patients treated with entecavir. Antivir Ther. 2013;18:691-8.
PubMed Abstract»
Gish RG, Lok AS, Chang TT, et al. Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B. Gastroenterology. 2007;133:1437-44.
PubMed Abstract»
Kariv R, Leshno M, Beth-Or A, et al. Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study. Liver Int. 2006;26:445-50.
PubMed Abstract»
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Kim BK, Kim DY, Park JY, et al. Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int. 2010;30:546-53.
PubMed Abstract»
Kim GA, Lim YS, Han S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut. 2018;67:945-52.
PubMed Abstract»
Li J, Gordon SC, Rupp LB, et al. The validity of serum markers for fibrosis staging in chronic hepatitis B and C. J Viral Hepat. 2014;21:930-7.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661-2.
PubMed Abstract»
Martin P, Lau DT, Nguyen MH, et al. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update. Clin Gastroenterol Hepatol. 2015;13:2071-87.e16.
PubMed Abstract»
Nana J, Skaare K, Bosson JL, et al. EASL-ALEH 2015 algorithm for the use of transient elastography in treatment-naive patients with hepatitis B: An independent validation. J Viral Hepat. 2021;28:1169-76.
PubMed Abstract»
Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int. 2016;36:1239-51.
PubMed Abstract»
Seto WK, Lo YR, Pawlotsky JM, Yuen MF. Chronic hepatitis B virus infection. Lancet. 2018;392:2313-24.
PubMed Abstract»
Sinn DH, Kim SE, Kim BK, Kim JH, Choi MS. The risk of hepatocellular carcinoma among chronic hepatitis B virus-infected patients outside current treatment criteria. J Viral Hepat. 2019 Jul 22. [Epub ahead of print]
PubMed Abstract»

Lesson 2. Choosing an Initial HBV Treatment Regimen

Module 2 » Lesson 2. Choosing an Initial HBV Treatment Regimen

Background

Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016;63:284-306.
PubMed Abstract»
Yuen MF, Ahn SH, Chen DS, et al. Chronic Hepatitis B Virus Infection: Disease Revisit and Management Recommendations. J Clin Gastroenterol. 2016;50:286-94.
PubMed Abstract»
Yuen MF, Chen DS, Dusheiko GM, et al. Hepatitis B virus infection. Nat Rev Dis Primers. 2018;4:18035.
PubMed Abstract»
Module 2 » Lesson 2. Choosing an Initial HBV Treatment Regimen

Oral Antiviral Therapy Options for HBV

Agarwal K, Brunetto M, Seto WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018;68:672-81.
PubMed Abstract»
Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134-44.
PubMed Abstract»
Ahn J, Lim JK, Lee HM, et al. Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study. Am J Gastroenterol. 2016;111:1297-304.
PubMed Abstract»
Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1:196-206.
PubMed Abstract»
Buti M, Riveiro-Barciela M, Esteban R. Long-term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B. Liver Int. 2018;38 Suppl 1:84-9.
PubMed Abstract»
Buti M, Tsai N, Petersen J, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015;60:1457-64.
PubMed Abstract»
Cathcart AL, Chan HL, Bhardwaj N, et al. No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection. Antimicrob Agents Chemother. 2018;62(10).pii: e01064-18
PubMed Abstract»
Chan HL, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1:185-95.
PubMed Abstract»
Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001-10.
PubMed Abstract»
Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886-93.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Lai CL, Dienstag J, Schiff E, et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis. 2003;36:687-96.
PubMed Abstract»
Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019;23:401-16.
PubMed Abstract»
Liu Y, Corsa AC, Buti M, et al. No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg- patients with chronic hepatitis B after 8 years of treatment. J Viral Hepat. 2017;24:68-74.
PubMed Abstract»
Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016;63:284-306.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-75.
PubMed Abstract»
Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442-55.
PubMed Abstract»
Nassal M. HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B. Gut. 2015;64:1972-84.
PubMed Abstract»
Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62:956-67.
PubMed Abstract»
Papatheodoridis GV, Sypsa V, Dalekos G, et al. Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population. J Hepatol. 2018;68:1129-36.
PubMed Abstract»
Seto WK, Lo YR, Pawlotsky JM, Yuen MF. Chronic hepatitis B virus infection. Lancet. 2018;392:2313-24.
PubMed Abstract»
Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018;319:1802-13.
PubMed Abstract»
Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology. 2009;49:1503-14.
PubMed Abstract»
Tenney DJ, Rose RE, Baldick CJ, et al. Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present. Antimicrob Agents Chemother. 2006;51:902-11.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Yuen MF, Fung J, Wong DK, Lai CL. Prevention and management of drug resistance for antihepatitis B treatment. Lancet Infect Dis. 2009;9:256-64.
PubMed Abstract»
Module 2 » Lesson 2. Choosing an Initial HBV Treatment Regimen

Peginterferon-Based Therapy for HBV

Buster EH, Flink HJ, Simsek H, et al. Early HBeAg loss during peginterferon alpha-2b therapy predicts HBsAg loss: results of a long-term follow-up study in chronic hepatitis B patients. Am J Gastroenterol. 2009;104:2449-57.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123-9.
PubMed Abstract»
Kao JH. HBeAg-positive chronic hepatitis B: why do I treat my patients with pegylated interferon? Liver Int. 2014;34 Suppl 1:112-9.
PubMed Abstract»
Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682-95.
PubMed Abstract»
Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442-55.
PubMed Abstract»
Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018;319:1802-13.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 2 » Lesson 2. Choosing an Initial HBV Treatment Regimen

Choosing Oral Antivirals versus Peginterferon

Ahn J, Lim JK, Lee HM, et al. Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study. Am J Gastroenterol. 2016;111:1297-304.
PubMed Abstract»
Bonino F, Marcellin P, Lau GK, et al. Predicting response to peginterferon alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B. Gut. 2007;56:699-705.
PubMed Abstract»
Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459-67.
PubMed Abstract»
Buster EH, Flink HJ, Simsek H, et al. Early HBeAg loss during peginterferon alpha-2b therapy predicts HBsAg loss: results of a long-term follow-up study in chronic hepatitis B patients. Am J Gastroenterol. 2009;104:2449-57.
PubMed Abstract»
Buster EH, Hansen BE, Buti M, et al. Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis. Hepatology. 2007;46:388-94.
PubMed Abstract»
Buti M, Riveiro-Barciela M, Esteban R. Long-term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B. Liver Int. 2018;38 Suppl 1:84-9.
PubMed Abstract»
Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886-93.
PubMed Abstract»
Cooksley G, Manns M, Lau GK, et al. Effect of genotype and other baseline factors on response to peginterferon alfa-2a (Pegasys) in HBeAg-positive chronic hepatitis B: Results from a large, randomized study. In: 40th Annual Meeting of the European Association for the Study of the Liver (EASL). Paris, France, 2005. Abstract 71.
no link available»
Cooksley WG, Piratvisuth T, Lee SD, et al. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat. 2003;10:298-305.
PubMed Abstract»
Cornberg M, Wong VW, Locarnini S, Brunetto M, Janssen HLA, Chan HL. The role of quantitative hepatitis B surface antigen revisited. J Hepatol. 2017;66:398-411.
PubMed Abstract»
Craxì A, Di Bona D, Cammà C. Interferon-alpha for HBeAg-positive chronic hepatitis B. J Hepatol. 2003;39 Suppl 1:S99-105.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Flink HJ, Sprengers D, Hansen BE, et al. Flares in chronic hepatitis B patients induced by the host or the virus? Relation to treatment response during Peg-interferon {alpha}-2b therapy. Gut. 2005;54:1604-9.
PubMed Abstract»
Flink HJ, van Zonneveld M, Hansen BE, de Man RA, Schalm SW, Janssen HL. Treatment with Peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype. Am J Gastroenterol. 2006;101:297-303.
PubMed Abstract»
Heathcote EJ, Marcellin P, Buti M, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology. 2011;140:132-43.
PubMed Abstract»
Janssen HL, Brouwer JT, Nevens F, Sanchez-Tapias JM, Craxi A, Hadziyannis S. Fatal hepatic decompensation associated with interferon alfa. European concerted action on viral hepatitis (Eurohep). BMJ. 1993;306:107-8.
PubMed Abstract»
Janssen HL, van Zonneveld M, Senturk H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123-9.
PubMed Abstract»
Kao JH. HBeAg-positive chronic hepatitis B: why do I treat my patients with pegylated interferon? Liver Int. 2014;34 Suppl 1:112-9.
PubMed Abstract»
Lau DT, Everhart J, Kleiner DE, et al. Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa. Gastroenterology. 1997;113:1660-7.
PubMed Abstract»
Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682-95.
PubMed Abstract»
Liang KH, Hsu CW, Chang ML, Chen YC, Lai MW, Yeh CT. Peginterferon Is Superior to Nucleos(t)ide Analogues for Prevention of Hepatocellular Carcinoma in Chronic Hepatitis B. J Infect Dis. 2016;213:966-74.
PubMed Abstract»
Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology. 1999;29:971-5.
PubMed Abstract»
Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016;63:284-306.
PubMed Abstract»
Marcellin P, Bonino F, Yurdaydin C, et al. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013;7:88-97.
PubMed Abstract»
Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-75.
PubMed Abstract»
Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004;351:1206-17.
PubMed Abstract»
Marcellin P, Piratvisuth T, Brunetto M, et al. Increasing rates of HBsAg clearance and seroconversion in patients with HBeAg-Negative disease treated with peginterferon ALFA-2A ± Lamivudine: Results of 5-year post-treatment follow up. J Hepatol 2009;50:S336.
Google Scholar»
Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med. 1996;334:1422-7.
PubMed Abstract»
Pavlovic V, Yang L, Chan HL, et al. Peginterferon alfa-2a (40 kD) stopping rules in chronic hepatitis B: a systematic review and meta-analysis of individual participant data. Antivir Ther. 2019;24:133-40.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804-10.
PubMed Abstract»
Yuen MF, Ahn SH, Chen DS, et al. Chronic Hepatitis B Virus Infection: Disease Revisit and Management Recommendations. J Clin Gastroenterol. 2016;50:286-94.
PubMed Abstract»
Yuen MF, Chen DS, Dusheiko GM, et al. Hepatitis B virus infection. Nat Rev Dis Primers. 2018;4:18035.
PubMed Abstract»
Zhao H, Si CW, Wei L, et al. A multicenter, randomized, open-label study of the safety and effectiveness of pegylated interferon alpha 2b and interferon alpha 2b in treating HBeAg positive chronic hepatitis B patients. 2006;14:323-6.
PubMed Abstract»
Module 2 » Lesson 2. Choosing an Initial HBV Treatment Regimen

Recommendations for Initial HBV Therapy

Arribas JR, Thompson M, Sax PE, et al. Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results. J Acquir Immune Defic Syndr. 2017;75:211-18.
PubMed Abstract»
Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1:196-206.
PubMed Abstract»
Chan HL, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016;1:185-95.
PubMed Abstract»
Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010;51:496-505.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21:70-84.
PubMed Abstract»
Gupta SK, Post FA, Arribas JR, et al. Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS. 2019;33:1455-65.
PubMed Abstract»
Lee HY, Oh H, Park CH, Yeo YH, Nguyen MH, Jun DW. Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis. World J Gastroenterol. 2019;25:2961-2972.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Toyoda H, Leong J, Landis C, et al. Treatment and Renal Outcomes Up to 96 Weeks After Tenofovir Alafenamide Switch From Tenofovir Disoproxil Fumarate in Routine Practice. Hepatology. 2021;74:656-66.
PubMed Abstract»
Zeng QL, Yu ZJ, Ji F, et al. Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study. Clin Infect Dis. 2021;73:e3324-e3332.
PubMed Abstract»
Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134-44.
PubMed Abstract»
Ahn J, Lim JK, Lee HM, et al. Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study. Am J Gastroenterol. 2016;111:1297-304.
PubMed Abstract»
Baldick CJ, Tenney DJ, Mazzucco CE, et al. Comprehensive evaluation of hepatitis B virus reverse transcriptase substitutions associated with entecavir resistance. Hepatology. 2008;47:1473-82.
PubMed Abstract»
Baqai S, Proudfoot J, Xu R, Kane S, Clark M, Gish R. Comparable efficacy with entecavir monotherapy and tenofovir-entecavir combination in chronic hepatitis B patients. BMJ Open Gastroenterol. 2015;2:e000030.
PubMed Abstract»
Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63:319-33.
PubMed Abstract»
Buster EH, Hansen BE, Lau GK, et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology. 2009;137:2002-9.
PubMed Abstract»
Buti M, Riveiro-Barciela M, Esteban R. Treatment of Chronic Hepatitis B Virus with Oral Anti-Viral Therapy. Clin Liver Dis. 2021;25:725-40.
PubMed Abstract»
Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001-10.
PubMed Abstract»
Chang TT, Gish RG, Hadziyannis SJ, et al. A dose-ranging study of the efficacy and tolerability of entecavir in lamivudine-refractory chronic hepatitis B patients. Gastroenterology. 2005;129:1198-1209.
PubMed Abstract»
Chang TT, Lai CL, Kew Yoon S, et al. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010;51:422-30.
PubMed Abstract»
Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010;52:886-93.
PubMed Abstract»
Cho YY, Chang Y, Nam JY, et al. Long-term Nucleotide Analogue Treatment Has Higher Levels of Renal Toxicities than Does Entecavir in Patients with Chronic Hepatitis B. Gut Liver. 2020;14:225-31.
PubMed Abstract»
Cohen C, Holmberg SD, McMahon BJ, et al. Is chronic hepatitis B being undertreated in the United States? J Viral Hepat. 2011;18:377-83.
PubMed Abstract»
Dienstag JL. Benefits and risks of nucleoside analog therapy for hepatitis B. Hepatology. 2009;49:S112-21.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Flemming JA, Terrault NA. Tenofovir vs Entecavir for hepatocellular carcinoma prevention in patients with chronic hepatitis B: one of these things Is not like the other. JAMA Oncol. 2019;5:17-18.
PubMed Abstract»
Gibson AK, Shah BM, Nambiar PH, Schafer JJ. Tenofovir Alafenamide. Ann Pharmacother. 2016;50:942-52.
PubMed Abstract»
Gish RG, Chang TT, Lai CL, et al. Loss of HBsAg antigen during treatment with entecavir or lamivudine in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. J Viral Hepat. 2009;17:16-22.
PubMed Abstract»
Gish RG, Chang TT, Lai CL, et al. Quantitative hepatitis B surface antigen analysis in hepatitis B e antigen-positive nucleoside-naive patients treated with entecavir. Antivir Ther. 2013;18:691-8.
PubMed Abstract»
Gish RG, Lok AS, Chang TT, et al. Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B. Gastroenterology. 2007;133:1437-44.
PubMed Abstract»
Huang ZH, Lu GY, Qiu LX, et al. Risk of hepatocellular carcinoma in antiviral treatment-naïve chronic hepatitis B patients treated with entecavir or tenofovir disoproxil fumarate: a network meta-analysis. BMC Cancer. 2022;22:287.
PubMed Abstract»
Hui CK, Zhang HY, Bowden S, et al. 96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B. J Hepatol. 2007;48:714-20.
PubMed Abstract»
Jacobson IM. Combination therapy for chronic hepatitis B: ready for prime time? J Hepatol. 2008;48:687-91.
PubMed Abstract»
Liang LY, Yip TC, Lai JC, et al. Tenofovir alafenamide is associated with improved alanine aminotransferase and renal safety compared to tenofovir disoproxil fumarate. J Med Virol. 2022;94:4440-8.
PubMed Abstract»
Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019;23:401-16.
PubMed Abstract»
Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016;63:284-306.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-75.
PubMed Abstract»
Marcellin P, Wong DK, Sievert W, et al. Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection. Liver Int. 2019;39:1868-75.
PubMed Abstract»
Martin P, Lau DT, Nguyen MH, et al. A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update. Clin Gastroenterol Hepatol. 2015;13:2071-87.e16.
PubMed Abstract»
Mateo L, Holgado S, Mariñoso ML, et al. Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients. Clin Rheumatol. 2016;35:1271-9.
PubMed Abstract»
Nash KL, Alexander GJ. The case for combination antiviral therapy for chronic hepatitis B virus infection. Lancet Infect Dis. 2008;8:444-8.
PubMed Abstract»
Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med. 1996;334:1422-7.
PubMed Abstract»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Seto WK, Lo YR, Pawlotsky JM, Yuen MF. Chronic hepatitis B virus infection. Lancet. 2018;392:2313-24.
PubMed Abstract»
Sung JJ, Lai JY, Zeuzem S, et al. Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B. J Hepatol. 2008;48:728-35.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Terrault NA. Benefits and risks of combination therapy for hepatitis B. Hepatology. 2009;49:S122-8.
PubMed Abstract»
US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update. March 2018:1-77.
CDC»
Wong GL, Chan HL, Tse YK, et al. Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment. Aliment Pharmacol Ther. 2018;48:984-92.
PubMed Abstract»

Lesson 3. Monitoring Persons On and Off HBV Therapy

Module 2 » Lesson 3. Monitoring Persons On and Off HBV Therapy

Introduction

McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009;49:S45-55.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 2 » Lesson 3. Monitoring Persons On and Off HBV Therapy

Monitoring Persons with Chronic HBV Who are Not on Treatment

European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Ghany MG. Current treatment guidelines of chronic hepatitis B: The role of nucleos(t)ide analogues and peginterferon. Best Pract Res Clin Gastroenterol. 2017;31:299-309.
PubMed Abstract»
Kim BK, Kim DY, Park JY, et al. Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int. 2010;30:546-53.
PubMed Abstract»
Li J, Gordon SC, Rupp LB, et al. The validity of serum markers for fibrosis staging in chronic hepatitis B and C. J Viral Hepat. 2014;21:930-7.
PubMed Abstract»
Li Y, Huang YS, Wang ZZ, et al. Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B. Aliment Pharmacol Ther. 2016;43:458-69.
PubMed Abstract»
Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
PubMed Abstract»
Seeff LB, Everson GT, Morgan TR, et al. Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol. 2010;8:877-83.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Villa E, Fattovich G, Mauro A, Pasino M. Natural history of chronic HBV infection: special emphasis on the prognostic implications of the inactive carrier state versus chronic hepatitis. Dig Liver Dis. 2011;43 Suppl 1:S8-14.
PubMed Abstract»
Module 2 » Lesson 3. Monitoring Persons On and Off HBV Therapy

Safety Monitoring in Persons with Chronic HBV on Treatment

Jung TY, Jun DW, Lee KN, et al. Fatal lactic acidosis in hepatitis B virus-associated decompensated cirrhosis treated with tenofovir: A case report. Medicine (Baltimore). 2017;96:e7133.
PubMed Abstract»
Lange CM, Bojunga J, Hofmann WP, et al. Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function. Hepatology. 2009;50:2001-6.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 2 » Lesson 3. Monitoring Persons On and Off HBV Therapy

Monitoring Treatment Response in Persons with Chronic HBV

Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134-44.
PubMed Abstract»
Buti M, Riveiro-Barciela M, Esteban R. Long-term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B. Liver Int. 2018;38 Suppl 1:84-9.
PubMed Abstract»
Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
PubMed Abstract»
Di Marco V, Marzano A, Lampertico P, et al. Clinical outcome of HBeAg-negative chronic hepatitis B in relation to virological response to lamivudine. Hepatology. 2004;40:883-91.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Ghany MG. Current treatment guidelines of chronic hepatitis B: The role of nucleos(t)ide analogues and peginterferon. Best Pract Res Clin Gastroenterol. 2017;31:299-309.
PubMed Abstract»
Iloeje UH, Yang HI, Jen CL, et al. Risk and predictors of mortality associated with chronic hepatitis B infection. Clin Gastroenterol Hepatol. 2007;5:921-31.
PubMed Abstract»
Kao JH. HBeAg-positive chronic hepatitis B: why do I treat my patients with pegylated interferon? Liver Int. 2014;34 Suppl 1:112-9.
PubMed Abstract»
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Kim JH, Sinn DH, Kang W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment. Hepatology. 2017;66:335-43.
PubMed Abstract»
Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-75.
PubMed Abstract»
Marcellin P, Zoulim F, Hézode C, et al. Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year, Prospective, Real-World Study in France. Dig Dis Sci. 2016;61:3072-83.
PubMed Abstract»
Nguyen MH, Keeffe EB. Chronic hepatitis B: early viral suppression and long-term outcomes of therapy with oral nucleos(t)ides. J Viral Hepat. 2009;16:149-55.
PubMed Abstract»
Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
PubMed Abstract»
Papatheodoridis G, Vlachogiannakos I, Cholongitas E, et al. Discontinuation of oral antivirals in chronic hepatitis B: A systematic review. Hepatology. 2016;63:1481-92.
PubMed Abstract»
Petersen J, Heyne R, Mauss S, et al. Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B: A 3-Year Prospective Field Practice Study in Germany. Dig Dis Sci. 2016;61:3061-71.
PubMed Abstract»
Seto WK, Lam YF, Fung J, et al. Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after 5 years of entecavir treatment. J Gastroenterol Hepatol. 2014;29:1028-34.
PubMed Abstract»
Sun Y, Wu X, Zhou J, et al. Persistent Low Level of Hepatitis B Virus Promotes Fibrosis Progression During Therapy. Clin Gastroenterol Hepatol. 2020;18:2582-91.e6.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Zeuzem S, Gane E, Liaw YF, et al. Baseline characteristics and early on-treatment response predict the outcomes of 2 years of telbivudine treatment of chronic hepatitis B. J Hepatol. 2009;51:11-20.
PubMed Abstract»
Module 2 » Lesson 3. Monitoring Persons On and Off HBV Therapy

Discontinuation of Antiviral Therapy Based on Treatment Response

Berg T, Lampertico P. The times they are a-changing - A refined proposal for finite HBV nucleos(t)ide analogue therapy. J Hepatol. 2021;75:474-80.
PubMed Abstract»
Berg T, Simon KG, Mauss S, et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J Hepatol. 2017;67:918-924.
PubMed Abstract»
Buti M, Riveiro-Barciela M, Esteban R. Long-term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B. Liver Int. 2018;38 Suppl 1:84-9.
PubMed Abstract»
Chang ML, Liaw YF, Hadziyannis SJ. Systematic review: cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B. Aliment Pharmacol Ther. 2015;42:243-57.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Jeng WJ, Chen YC, Chien RN, Sheen IS, Liaw YF. Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2018;68:425-34.
PubMed Abstract»
Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Gut. 2002;51:597-9.
PubMed Abstract»
Marcellin P, Bonino F, Lau GK, et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology. 2009;136:2169-79.
PubMed Abstract»
Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
PubMed Abstract»
Papatheodoridis G, Vlachogiannakos I, Cholongitas E, et al. Discontinuation of oral antivirals in chronic hepatitis B: A systematic review. Hepatology. 2016;63:1481-92.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»

Additional References

Ahn J, Lee HM, Lim JK, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134-44.
PubMed Abstract»
Buti M, Riveiro-Barciela M, Esteban R. Long-term safety and efficacy of nucleo(t)side analogue therapy in hepatitis B. Liver Int. 2018;38 Suppl 1:84-9.
PubMed Abstract»
Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Ghany MG. Current treatment guidelines of chronic hepatitis B: The role of nucleos(t)ide analogues and peginterferon. Best Pract Res Clin Gastroenterol. 2017;31:299-309.
PubMed Abstract»
Kao JH. HBeAg-positive chronic hepatitis B: why do I treat my patients with pegylated interferon? Liver Int. 2014;34 Suppl 1:112-9.
PubMed Abstract»
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Kim BK, Kim DY, Park JY, et al. Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int. 2010;30:546-53.
PubMed Abstract»
Li J, Gordon SC, Rupp LB, et al. The validity of serum markers for fibrosis staging in chronic hepatitis B and C. J Viral Hepat. 2014;21:930-7.
PubMed Abstract»
Li Y, Huang YS, Wang ZZ, et al. Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B. Aliment Pharmacol Ther. 2016;43:458-69.
PubMed Abstract»
Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468-75.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009;49:S45-55.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Wong GL, Seto WK, Wong VW, Yuen MF, Chan HL. Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B. Aliment Pharmacol Ther. 2018;47:730-737.
PubMed Abstract»

Module 3. Screening and Diagnosis

Lesson 1. HBV Epidemiology

Module 3 » Lesson 1. HBV Epidemiology

Background

Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Hu J, Protzer U, Siddiqui A. Revisiting Hepatitis B Virus: Challenges of Curative Therapies. J Virol. 2019;93:pii: e01032-19.
PubMed Abstract»
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56:422-33.
PubMed Abstract»
Patel EU, Thio CL, Boon D, Thomas DL, Tobian AAR. Prevalence of Hepatitis B and Hepatitis D Virus Infections in the United States, 2011-2016. Clin Infect Dis. 2019 Jan 3. [Epub ahead of print]
PubMed Abstract»
Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63:388-97.
PubMed Abstract»
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
PubMed Abstract»
World Health Organization. Global Hepatitis Report 2017. Geneva: World Health Organization; April, 2017:1-83.
WHO»
Module 3 » Lesson 1. HBV Epidemiology

HBV Incidence in the United States

Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44:S6-9.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Centers for Disease Control and Prevention (CDC). National Notifiable Diseases Surveillance System (NNDSS). Hepatitis B, Acute 2012 Case Definition.
CDC»
Kim HB, Kim WR. Epidemiology of Hepatitis B Virus Infection in the United States. Clin Liver Dis (Hoboken). 2018;12:1-4.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
PubMed Abstract»
Module 3 » Lesson 1. HBV Epidemiology

HBV Prevalence in the United States

Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Centers for Disease Control and Prevention (CDC). National Notifiable Diseases Surveillance System (NNDSS). Hepatitis B, Chronic 2012 Case Definition.
CDC»
Ioannou GN. Hepatitis B virus in the United States: infection, exposure, and immunity rates in a nationally representative survey. Ann Intern Med. 2011;154:319-28.
PubMed Abstract»
Kim HB, Kim WR. Epidemiology of Hepatitis B Virus Infection in the United States. Clin Liver Dis (Hoboken). 2018;12:1-4.
PubMed Abstract»
Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49:S28-34.
PubMed Abstract»
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56:422-33.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Patel EU, Thio CL, Boon D, Thomas DL, Tobian AAR. Prevalence of Hepatitis B and Hepatitis D Virus Infections in the United States, 2011-2016. Clin Infect Dis. 2019 Jan 3. [Epub ahead of print]
PubMed Abstract»
Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63:388-97.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Wasley A, Kruszon-Moran D, Kuhnert W, et al. The prevalence of hepatitis B virus infection in the United States in the era of vaccination. J Infect Dis. 2010;202:192-201.
PubMed Abstract»
Wong RJ, Brosgart CL, Welch S, et al. An Updated Assessment of Chronic Hepatitis B Prevalence Among Foreign-Born Persons Living in the United States. Hepatology. 2021;74:607-26.
PubMed Abstract»
Module 3 » Lesson 1. HBV Epidemiology

Awareness of HBV Infection Status

Kim HB, Kim WR. Epidemiology of Hepatitis B Virus Infection in the United States. Clin Liver Dis (Hoboken). 2018;12:1-4.
PubMed Abstract»
Kim HS, Rotundo L, Yang JD, et al. Racial/ethnic disparities in the prevalence and awareness of Hepatitis B virus infection and immunity in the United States. J Viral Hepat. 2017;24:1052-66.
PubMed Abstract»
Kim HS, Yang JD, El-Serag HB, Kanwal F. Awareness of chronic viral hepatitis in the United States: An update from the National Health and Nutrition Examination Survey. J Viral Hepat. 2019;26:596-602.
PubMed Abstract»
Zhou K, Terrault NA. Gaps in Viral Hepatitis Awareness in the United States in a Population-based Study. Clin Gastroenterol Hepatol. 2019;pii: S1542-3565(19)30598-1.
PubMed Abstract»
Module 3 » Lesson 1. HBV Epidemiology

Global HBV Epidemiology

Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep. 2023;72:1-25.
PubMed Abstract»
Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378:571-83.
PubMed Abstract»
Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3:383-403.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546-55.
PubMed Abstract»
Thomas DL. Global Elimination of Chronic Hepatitis. N Engl J Med. 2019;380:2041-50.
PubMed Abstract»
World Health Organization. (‎2019)‎. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021: accountability for the global health sector strategies, 2016–2021. World Health Organization. July 15, 2021.
WHO»
World Health Organization. Global health sector strategy on viral hepatitis 2016-2021. June 2016:1-56.
WHO»
World Health Organization. Global Hepatitis Report 2017. Geneva: World Health Organization; April, 2017:1-83.
WHO»
World Health Organization. Hepatitis B: Key Facts. Geneva: World Health Organization; June 24, 2022.
WHO»
Module 3 » Lesson 1. HBV Epidemiology

Risks Associated with HBV Acquisition

Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44:S6-9.
PubMed Abstract»
Beasley RP, Hwang LY, Lee GC, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;2:1099-102.
PubMed Abstract»
Bosh KA, Coyle JR, Hansen V, et al. HIV and viral hepatitis coinfection analysis using surveillance data from 15 US states and two cities. Epidemiol Infect. 2018;146:920-30.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Chen G, Wang C, Chen J, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis. Hepatology. 2017;66:13-26.
PubMed Abstract»
Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18:52-61.
PubMed Abstract»
Gupta S, Altice FL. Hepatitis B virus infection in US correctional facilities: a review of diagnosis, management, and public health implications. J Urban Health. 2009;86:263-79.
PubMed Abstract»
Harris AM, Iqbal K, Schillie S, et al. Increases in Acute Hepatitis B Virus Infections - Kentucky, Tennessee, and West Virginia, 2006-2013. MMWR Morb Mortal Wkly Rep. 2016;65:47-50.
PubMed Abstract»
Huprikar S, Danziger-Isakov L, Ahn J, et al. Solid organ transplantation from hepatitis B virus-positive donors: consensus guidelines for recipient management. Am J Transplant. 2015;15:1162-72.
PubMed Abstract»
Iqbal K, Klevens RM, Kainer MA, et al. Epidemiology of Acute Hepatitis B in the United States From Population-Based Surveillance, 2006-2011. Clin Infect Dis. 2015;61:584-92.
PubMed Abstract»
Johnson DF, Leder K, Torresi J. Hepatitis B and C infection in international travelers. J Travel Med. 2013;20:194-202.
PubMed Abstract»
Kellerman SE, Hanson DL, McNaghten AD, Fleming PL. Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. J Infect Dis. 2003;188:571-7.
PubMed Abstract»
Kim WR. Epidemiology of hepatitis B in the United States. Hepatology. 2009;49:S28-34.
PubMed Abstract»
Ko SC, Fan L, Smith EA, Fenlon N, Koneru AK, Murphy TV. Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000-2009. J Pediatric Infect Dis Soc. 2016;5:114-21.
PubMed Abstract»
Kowdley KV, Wang CC, Welch S, Roberts H, Brosgart CL. Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin. Hepatology. 2012;56:422-33.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Moorman AC, Xing J, Rupp LB, et al. Hepatitis B Virus Infection and Hepatitis C Virus Treatment in a Large Cohort of Hepatitis C-Infected Patients in the United States. Gastroenterology. 2018;154:754-758.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378:571-83.
PubMed Abstract»
Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30:2212-9.
PubMed Abstract»
Owens DK, Davidson KW, Krist AH, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
Polish LB, Shapiro CN, Bauer F, et al. Nosocomial transmission of hepatitis B virus associated with the use of a spring-loaded finger-stick device. N Engl J Med. 1992;326:721-5.
PubMed Abstract»
Puoti M, Airoldi M, Bruno R, et al. Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects. AIDS Rev. 2002;4:27-35.
PubMed Abstract»
Roberts H, Kruszon-Moran D, Ly KN, et al. Prevalence of chronic hepatitis B virus (HBV) infection in U.S. households: National Health and Nutrition Examination Survey (NHANES), 1988-2012. Hepatology. 2016;63:388-97.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Schillie SF, Xing J, Murphy TV, Hu DJ. Prevalence of hepatitis B virus infection among persons with diagnosed diabetes mellitus in the United States, 1999-2010. J Viral Hepat. 2012;19:674-6.
PubMed Abstract»
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546-55.
PubMed Abstract»
Shing JZ, Ly KN, Xing J, Teshale EH, Jiles RB. Prevalence of Hepatitis B Virus Infection among US Adults Aged 20-59 Years with a History of Injection Drug Use: National Health and Nutrition Examination Survey, 2001-2016. Clin Infect Dis. 2019 Jul 27. [Epub ahead of print]
PubMed Abstract»
Stevens CE, Taylor PE, Tong MJ, et al. Yeast-recombinant hepatitis B vaccine. Efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission. JAMA. 1987;257:2612-6.
PubMed Abstract»
Stramer SL, Notari EP, Krysztof DE, Dodd RY. Hepatitis B virus testing by minipool nucleic acid testing: does it improve blood safety? Transfusion. 2013;53:2449-58.
PubMed Abstract»
Thompson ND, Perz JF, Moorman AC, Holmberg SD. Nonhospital health care-associated hepatitis B and C virus transmission: United States, 1998-2008. Ann Intern Med. 2009 ;150:33-9.
PubMed Abstract»
Tyson GL, Kramer JR, Duan Z, Davila JA, Richardson PA, El-Serag HB. Prevalence and predictors of hepatitis B virus coinfection in a United States cohort of hepatitis C virus-infected patients. Hepatology. 2013;58:538-45.
PubMed Abstract»
Weinbaum C, Lyerla R, Margolis HS. Prevention and control of infections with hepatitis viruses in correctional settings. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2003;52:1-36.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Williams RE, Sena AC, Moorman AC, et al. Hepatitis B vaccination of susceptible elderly residents of long term care facilities during a hepatitis B outbreak. Vaccine. 2012;30:3147-50.
PubMed Abstract»
Woodruff BA, Vazquez E. Prevalence of hepatitis virus infections in an institution for persons with developmental disabilities. Am J Ment Retard. 2002;107:278-92.
PubMed Abstract»
Xu ZY, Liu CB, Francis DP, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial. Pediatrics. 1985;76:713-8.
PubMed Abstract»
Zibbell JE, Iqbal K, Patel RC, et al. Increases in hepatitis C virus infection related to injection drug use among persons aged ≤30 years - Kentucky, Tennessee, Virginia, and West Virginia, 2006-2012. MMWR Morb Mortal Wkly Rep. 2015;64:453-8.
PubMed Abstract»
Module 3 » Lesson 1. HBV Epidemiology

CDC Case Definition and Reporting

Centers for Disease Control and Prevention (CDC). National Notifiable Diseases Surveillance System (NNDSS). Hepatitis B, Acute 2012 Case Definition.
CDC»
Centers for Disease Control and Prevention (CDC). National Notifiable Diseases Surveillance System (NNDSS). Hepatitis B, Chronic 2012 Case Definition.
CDC»
Centers for Disease Control and Prevention (CDC). National Notifiable Diseases Surveillance System (NNDSS). Hepatitis B, Perinatal Infection 2017 Case Definition
CDC»
Module 3 » Lesson 1. HBV Epidemiology

HBV Disease Burden

Bixler D, Zhong Y, Ly KN, et al. Mortality Among Patients With Chronic Hepatitis B Infection: The Chronic Hepatitis Cohort Study (CHeCS). Clin Infect Dis. 2019;68:956-963.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018;392:2052-90.
PubMed Abstract»
Thomas DL. Global Elimination of Chronic Hepatitis. N Engl J Med. 2019;380:2041-50.
PubMed Abstract»
World Health Organization. (‎2019)‎. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021: accountability for the global health sector strategies, 2016–2021. World Health Organization. July 15, 2021.
WHO»
World Health Organization. Global Hepatitis Report 2017. Geneva: World Health Organization; April, 2017:1-83.
WHO»
Di Bisceglie AM, King WC, Lisker-Melman M, et al. Age, race and viral genotype are associated with the prevalence of hepatitis B e antigen in children and adults with chronic hepatitis B. J Viral Hepat. 2019;26:856-865.
PubMed Abstract»
Ha E, Kim F, Blanchard J, Juon HS. Prevalence of Chronic Hepatitis B and C Infection in Mongolian Immigrants in the Washington, District of Columbia, Metropolitan Area, 2016-2017. Prev Chronic Dis. 2019;16:E08.
PubMed Abstract»
Hyun Kim B, Ray Kim W. Epidemiology of Hepatitis B Virus Infection in the United States. Clin Liver Dis (Hoboken). 2018;12:1-4.
PubMed Abstract»
Mitchell T, Armstrong GL, Hu DJ, Wasley A, Painter JA. The increasing burden of imported chronic hepatitis B--United States, 1974-2008. PLoS One. 2011;6:e27717.
PubMed Abstract»
Nguyen MH, Lim JK, Burak Ozbay A, et al. Advancing Age and Comorbidity in a US Insured Population-Based Cohort of Patients With Chronic Hepatitis B. Hepatology. 2019;69:959-73.
PubMed Abstract»
Ramachandran S, Purdy MA, Xia GL, et al. Recent population expansions of hepatitis B virus in the United States. J Virol. 2014;88:13971-80.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Scott KC, Taylor EM, Mamo B, et al. Hepatitis B screening and prevalence among resettled refugees - United States, 2006-2011. MMWR Morb Mortal Wkly Rep. 2015;64:570-3.
PubMed Abstract»
Smith JM, Uvin AZ, Macmadu A, Rich JD. Epidemiology and Treatment of Hepatitis B in Prisoners. Curr Hepatol Rep. 2017;16:178-183.
PubMed Abstract»
US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
World Health Organization. Interim guidance for country validation of viral hepatitis elimination. Geneva: World Health Organization; June 8, 2021.
WHO»

Lesson 2. HBV Screening, Testing, and Diagnosis

Module 3 » Lesson 2. HBV Screening, Testing, and Diagnosis

HBV Screening Recommendations

Abara WE, Qaseem A, Schillie S, McMahon BJ, Harris AM. Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2017;167:794-804.
PubMed Abstract»
Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep. 2023;72:1-25.
PubMed Abstract»
Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358-80.
PubMed Abstract»
LeFevre ML. Screening for hepatitis B virus infection in nonpregnant adolescents and adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161:58-66.
PubMed Abstract»
Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019;23:401-16.
PubMed Abstract»
Seto WK, Lo YR, Pawlotsky JM, Yuen MF. Chronic hepatitis B virus infection. Lancet. 2018;392:2313-24.
PubMed Abstract»
Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018;319:1802-13.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Toy M, Hutton D, Harris AM, Nelson N, Salomon JA, So S. Cost-Effectiveness of 1-Time Universal Screening for Chronic Hepatitis B Infection in Adults in the United States. Clin Infect Dis. 2022;74:210-17.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Module 3 » Lesson 2. HBV Screening, Testing, and Diagnosis

Recommended Screening Tests

Abara WE, Qaseem A, Schillie S, McMahon BJ, Harris AM. Hepatitis B Vaccination, Screening, and Linkage to Care: Best Practice Advice From the American College of Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2017;167:794-804.
PubMed Abstract»
Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep. 2023;72:1-25.
PubMed Abstract»
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev. 2006;:CD004790.
PubMed Abstract»
LeFevre ML. Screening for hepatitis B virus infection in nonpregnant adolescents and adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;161:58-66.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Module 3 » Lesson 2. HBV Screening, Testing, and Diagnosis

Incorporation of HBV Screening into Clinical Workflows

Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep. 2023;72:1-25.
PubMed Abstract»
Module 3 » Lesson 2. HBV Screening, Testing, and Diagnosis

Evolution of Serologic Tests after Infection and Vaccination

Bruce MG, Bruden D, Hurlburt D, et al. Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. J Infect Dis. 2016;214:16-22.
PubMed Abstract»
Hadziyannis SJ, Papatheodoridis GV. Hepatitis B e antigen-negative chronic hepatitis B: natural history and treatment. Semin Liver Dis. 2006;26:130-41.
PubMed Abstract»
McMahon BJ, Dentinger CM, Bruden D, et al. Antibody levels and protection after hepatitis B vaccine: results of a 22-year follow-up study and response to a booster dose. J Infect Dis. 2009;200:1390-6.
PubMed Abstract»
Module 3 » Lesson 2. HBV Screening, Testing, and Diagnosis

Interpretation of HBV Serologic Tests

Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118-29.
PubMed Abstract»
Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med. 1986;315:209-14.
PubMed Abstract»
Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Lada O, Benhamou Y, Poynard T, Thibault V. Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of "a" determinant variants. J Virol. 2006;80:2968-75.
PubMed Abstract»
Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337:1733-45.
PubMed Abstract»
Mahoney FJ. Update on diagnosis, management, and prevention of hepatitis B virus infection. Clin Microbiol Rev. 1999;12:351-66.
PubMed Abstract»
Mushahwar IK, Dienstag JL, Polesky HF, McGrath LC, Decker RH, Overby LR. Interpretation of various serological profiles of hepatitis B virus infection. Am J Clin Pathol. 1981;76:773-7.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Zhang JM, Xu Y, Wang XY, et al. Coexistence of hepatitis B surface antigen (HBsAg) and heterologous subtype-specific antibodies to HBsAg among patients with chronic hepatitis B virus infection. Clin Infect Dis. 2007;44:1161-9.
PubMed Abstract»
Aldershvile J, Frösner GG, Nielsen JO, Hardt F, Deinhardt F, Skinhøj P. Hepatitis B e antigen and antibody measured by radioimmunoassay in acute hepatitis B surface antigen-positive hepatitis. J Infect Dis. 1980;141:293-8.
PubMed Abstract»
Aldershvile J, Nielsen JO. HBeAg, anti-HBe and anti-HBc IgM in patients with hepatitis B. J Virol Methods. 1980;2:97-105.
PubMed Abstract»
Alhababi F, Sallam TA, Tong CY. The significance of 'anti-HBc only' in the clinical virology laboratory. J Clin Virol. 2003;27:162-9.
PubMed Abstract»
Almeida Neto C, Strauss E, Sabino EC, Sucupira MC, Chamone DA. Significance of isolated hepatitis B core antibody in blood donors from São Paulo. Rev Inst Med Trop Sao Paulo. 2001;43:203-8.
PubMed Abstract»
Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Orlando ME, Raimondo G. Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease. N Engl J Med. 1999;341:22-6.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part 1 Immunization of Infants, Children, and Adolescents. MMWR Morb Mortal Wkly Rep. 2005;54(RR-16):1-23.
CDC»
Chahal HS, Peters MG, Harris AM, McCabe D, Volberding P, Kahn JG. Cost-effectiveness of Hepatitis B Virus Infection Screening and Treatment or Vaccination in 6 High-risk Populations in the United States. Open Forum Infect Dis. 2019;6:ofy353.
PubMed Abstract»
Chou R, Dana T, Bougatsos C, Blazina I, Khangura J, Zakher B. Screening for hepatitis B virus infection in adolescents and adults: a systematic review to update the U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2014;161:31-45.
PubMed Abstract»
Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep. 2023;72:1-25.
PubMed Abstract»
De Feo TM, Grossi P, Poli F, et al. Kidney transplantation from anti-HBc+ donors: results from a retrospective Italian study. Transplantation. 2006;81:76-80.
PubMed Abstract»
Dickson RC, Everhart JE, Lake JR, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. Gastroenterology. 1997;113:1668-74.
PubMed Abstract»
Douglas DD, Taswell HF, Rakela J, Rabe D. Absence of hepatitis B virus DNA detected by polymerase chain reaction in blood donors who are hepatitis B surface antigen negative and antibody to hepatitis B core antigen positive from a United States population with a low prevalence of hepatitis B serologic markers. Transfusion. 1993;33:212-6.
PubMed Abstract»
Fong TL, Bunnapradist S, Jordan SC, Cho YW. Impact of hepatitis B core antibody status on outcomes of cadaveric renal transplantation: analysis of United network of organ sharing database between 1994 and 1999. Transplantation. 2002;73:85-9.
PubMed Abstract»
French AL, Operskalski E, Peters M, et al. Isolated hepatitis B core antibody is associated with HIV and ongoing but not resolved hepatitis C virus infection in a cohort of US women. J Infect Dis. 2007;195:1437-42.
PubMed Abstract»
Gandhi RT, Wurcel A, Lee H, et al. Isolated antibody to hepatitis B core antigen in human immunodeficiency virus type-1-infected individuals. Clin Infect Dis. 2003;36:1602-5.
PubMed Abstract»
Gandhi RT, Wurcel A, McGovern B, et al. Low prevalence of ongoing hepatitis B viremia in HIV-positive individuals with isolated antibody to hepatitis B core antigen. J Acquir Immune Defic Syndr. 2003;34:439-41.
PubMed Abstract»
Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118-29.
PubMed Abstract»
Gibney KB, Torresi J, Lemoh C, Biggs BA. Isolated core antibody hepatitis B in sub-Saharan African immigrants. J Med Virol. 2008;80:1565-9.
PubMed Abstract»
Gow PJ, Mutimer DJ. De novo hepatitis B infection acquired during liver transplantation. QJM. 2001;94:271-5.
PubMed Abstract»
Harris AM, Schoenbachler BT, Ramirez G, Vellozzi C, Beckett GA. Testing and Linking Foreign-Born People with Chronic Hepatitis B Virus Infection to Care at Nine U.S. Programs, 2012-2014. Public Health Rep. 2016;131 Suppl 2:20-8.
PubMed Abstract»
Hennig H, Puchta I, Luhm J, Schlenke P, Goerg S, Kirchner H. Frequency and load of hepatitis B virus DNA in first-time blood donors with antibodies to hepatitis B core antigen. Blood. 2002;100:2637-41.
PubMed Abstract»
Holt D, Thomas R, Van Thiel D, Brems JJ. Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation. Arch Surg. 2002;137:572-5.
PubMed Abstract»
Hoofnagle JH, Feinstone SM. Serological tests for non-A, non-B hepatitis: controversy. Liver. 1981;1:177-82.
PubMed Abstract»
Hoofnagle JH, Seeff LB, Bales ZB, Zimmerman HJ. Type B hepatitis after transfusion with blood containing antibody to hepatitis B core antigen. N Engl J Med. 1978;298:1379-83.
PubMed Abstract»
Hui CK, Cheung WW, Zhang HY, et al. Kinetics and risk of de novo hepatitis B infection in HBsAg-negative patients undergoing cytotoxic chemotherapy. Gastroenterology. 2006;131:59-68.
PubMed Abstract»
Joller-Jemelka HI, Wicki AN, Grob PJ. Detection of HBs antigen in "anti-HBc alone" positive sera. J Hepatol. 1994;21:269-72.
PubMed Abstract»
Kitchen AD, Harrison TJ, Meacock TJ, Zuckerman AJ, Harrison JF. Incidence and significance of hepatitis B core antibody in a healthy blood donor population. J Med Virol. 1988;25:69-75.
PubMed Abstract»
Krajden M, McNabb G, Petric M. The laboratory diagnosis of hepatitis B virus. Can J Infect Dis Med Microbiol. 2005;16:65-72.
PubMed Abstract»
Krogsgaard K, Aldershvile J, Kryger P, Andersson P, Nielsen JO, Hansson BG. Hepatitis B virus DNA, HBeAg and delta infection during the course from acute to chronic hepatitis B virus infection. Hepatology. 1985;5:778-82.
PubMed Abstract»
Likhitsup A, Lok AS. Understanding the Natural History of Hepatitis B Virus Infection and the New Definitions of Cure and the Endpoints of Clinical Trials. Clin Liver Dis. 2019;23:401-16.
PubMed Abstract»
Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, Morgan TR. Occult and previous hepatitis B virus infection are not associated with hepatocellular carcinoma in United States patients with chronic hepatitis C. Hepatology. 2011;54:434-42.
PubMed Abstract»
Lok AS, Lai CL, Wu PC. Prevalence of isolated antibody to hepatitis B core antigen in an area endemic for hepatitis B virus infection: implications in hepatitis B vaccination programs. Hepatology. 1988;8:766-70.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Matsue K, Kimura S, Takanashi Y, et al. Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-positive B-cell lymphoma. Cancer. 2010;116:4769-76.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Pawlotsky JM. The concept of hepatitis B virus mutant escape. J Clin Virol. 2005;34 Suppl 1:S125-9.
PubMed Abstract»
Peeling RW, Boeras DI, Marinucci F, Easterbrook P. The future of viral hepatitis testing: innovations in testing technologies and approaches. BMC Infect Dis. 2017;17:699.
PubMed Abstract»
Prieto M, Gómez MD, Berenguer M, et al. De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population. Liver Transpl. 2001;7:51-8.
PubMed Abstract»
Puoti M, Airoldi M, Bruno R, et al. Hepatitis B virus co-infection in human immunodeficiency virus-infected subjects. AIDS Rev. 2002;4:27-35.
PubMed Abstract»
Quaglio G, Lugoboni F, Vento S, et al. Isolated presence of antibody to hepatitis B core antigen in injection drug users: do they need to be vaccinated? Clin Infect Dis. 2001;32:E143-4.
PubMed Abstract»
Ramirez G, Cabral R, Patterson M, et al. Early Identification and Linkage to Care for People with Chronic HBV and HCV Infection: The HepTLC Initiative. Public Health Rep. 2016;131 Suppl 2:5-11.
PubMed Abstract»
Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med. 1996;2:1104-8.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schmeltzer P, Sherman KE. Occult hepatitis B: clinical implications and treatment decisions. Dig Dis Sci. 2010;55:3328-35.
PubMed Abstract»
Seto WK, Lo YR, Pawlotsky JM, Yuen MF. Chronic hepatitis B virus infection. Lancet. 2018;392:2313-24.
PubMed Abstract»
Silva AE, McMahon BJ, Parkinson AJ, Sjogren MH, Hoofnagle JH, Di Bisceglie AM. Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine. Clin Infect Dis. 1998;26:895-7.
PubMed Abstract»
Suehiro T, Shimada M, Kishikawa K, et al. Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation. Liver Int. 2005;25:1169-74.
PubMed Abstract»
Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018;319:1802-13.
PubMed Abstract»
Tedder RS, Ijaz S, Gilbert N, et al. Evidence for a dynamic host-parasite relationship in e-negative hepatitis B carriers. J Med Virol. 2002;68:505-12.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Tong S, Kim KH, Chante C, Wands J, Li J. Hepatitis B Virus e Antigen Variants. Int J Med Sci. 2005;2:2-7.
PubMed Abstract»
Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002;2:479-86.
PubMed Abstract»
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
PubMed Abstract»
Tsang TK, Blei AT, O'Reilly DJ, Decker R. Clinical significance of concurrent hepatitis B surface antigen and antibody positivity. Dig Dis Sci. 1986;31:620-4.
PubMed Abstract»
US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
Weber B, Melchior W, Gehrke R, Doerr HW, Berger A, Rabenau H. Hepatitis B virus markers in anti-HBc only positive individuals. J Med Virol. 2001;64:312-9.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Witt MD, Lewis RJ, Rieg G, Seaberg EC, Rinaldo CR, Thio CL. Predictors of the isolated hepatitis B core antibody pattern in HIV-infected and -uninfected men in the multicenter AIDS cohort study. Clin Infect Dis. 2012;56:606-12.
PubMed Abstract»

Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

General Approach to the Initial Evaluation

Fontana RJ. Evaluation of the patient with chronic hepatitis B. Clin Liver Dis (Hoboken). 2013;2:1-4.
PubMed Abstract»
Mushahwar IK, Dienstag JL, Polesky HF, McGrath LC, Decker RH, Overby LR. Interpretation of various serological profiles of hepatitis B virus infection. Am J Clin Pathol. 1981;76:773-7.
PubMed Abstract»
Rotman Y, Brown TA, Hoofnagle JH. Evaluation of the patient with hepatitis B. Hepatology. 2009;49:S22-7.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
PubMed Abstract»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Key Aspects of Medical History

Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:328-43.
PubMed Abstract»
Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998;158:1789-95.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142:1592-609.
PubMed Abstract»
Czaja AJ. Review article: next-generation transformative advances in the pathogenesis and management of autoimmune hepatitis. Aliment Pharmacol Ther. 2017;46:920-37.
PubMed Abstract»
Diehl AM, Day C. Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis. N Engl J Med. 2017;377:2063-72.
PubMed Abstract»
Donato F, Tagger A, Gelatti U, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155:323-31.
PubMed Abstract»
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-76.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Ewing JA. Detecting alcoholism. The CAGE questionnaire. JAMA. 1984;252:1905-7.
PubMed Abstract»
Guillevin L, Lhote F, Cohen P, et al. Polyarteritis nodosa related to hepatitis B virus. A prospective study with long-term observation of 41 patients. Medicine (Baltimore). 1995;74:238-53.
PubMed Abstract»
Han SH. Extrahepatic manifestations of chronic hepatitis B. Clin Liver Dis. 2004;8:403-18.
PubMed Abstract»
Iida-Ueno A, Enomoto M, Tamori A, Kawada N. Hepatitis B virus infection and alcohol consumption. World J Gastroenterol. 2017;23:2651-9.
PubMed Abstract»
Ikeda K, Saitoh S, Suzuki Y, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol. 1998;28:930-8.
PubMed Abstract»
Jamma S, Hussain G, Lau DT. Current Concepts of HBV/HCV Coinfection: Coexistence, but Not Necessarily in Harmony. Curr Hepat Rep. 2010;9:260-9.
PubMed Abstract»
Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990;37:663-76.
PubMed Abstract»
Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006;354:54-66.
PubMed Abstract»
Lai CL, Dienstag J, Schiff E, et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis. 2003;36:687-96.
PubMed Abstract»
Lai KN, Lai FM, Chan KW, Chow CB, Tong KL, Vallance-Owen J. The clinico-pathologic features of hepatitis B virus-associated glomerulonephritis. Q J Med. 1987;63:323-33.
PubMed Abstract»
Lin CW, Lin CC, Mo LR, et al. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol. 2013;58:730-5.
PubMed Abstract»
Mazzaro C, Adinolfi LE, Pozzato G, et al. Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy. J Clin Med. 2022;11:1:6247.
PubMed Abstract»
McMahon MA, Jilek BL, Brennan TP, et al. The HBV drug entecavir - effects on HIV-1 replication and resistance. N Engl J Med. 2007;356:2614-21.
PubMed Abstract»
National Institute on Alcohol Abuse and Alcoholism. Rethinking drinking: alcohol and your health. What counts as a Drink?
NIAA»
Nelson DR, Teckman J, Di Bisceglie AM, Brenner DA. Diagnosis and management of patients with α1-antitrypsin (A1AT) deficiency. Clin Gastroenterol Hepatol. 2012;10:575-80.
PubMed Abstract»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Pappachan JM, Babu S, Krishnan B, Ravindran NC. Non-alcoholic Fatty Liver Disease: A Clinical Update. J Clin Transl Hepatol. 2017;5:384-93.
PubMed Abstract»
Pascale A, Pais R, Ratziu V. An overview of nonalcoholic steatohepatitis: past, present and future directions. J Gastrointestin Liver Dis. 2010;19:415-23.
PubMed Abstract»
Rotman Y, Brown TA, Hoofnagle JH. Evaluation of the patient with hepatitis B. Hepatology. 2009;49:S22-7.
PubMed Abstract»
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993;88:791-804.
PubMed Abstract»
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546-55.
PubMed Abstract»
Shah PA, Choudhry S, Reyes KJC, Lau DTY. An update on the management of chronic hepatitis D. Gastroenterol Rep (Oxf). 2019;7:396-402.
PubMed Abstract»
Singh KP, Crane M, Audsley J, Avihingsanon A, Sasadeusz J, Lewin SR. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. AIDS. 2017;31:2035-2052.
PubMed Abstract»
Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis. J Hepatol. 2020;73:523-32.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Win NN, Kanda T, Ogawa M, et al. Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus. Int J Med Sci. 2019;16:1366-70.
PubMed Abstract»
World Health Organization. Global hepatitis report, 2017. April, 2017:1-68.
WHO»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Key Aspects of the Physical Examination

Braunstein GD. Clinical practice. Gynecomastia. N Engl J Med. 2007;357:1229-37.
PubMed Abstract»
Cattau EL Jr, Benjamin SB, Knuff TE, Castell DO. The accuracy of the physical examination in the diagnosis of suspected ascites. JAMA. 1982;247:1164-6.
PubMed Abstract»
de Bruyn G, Graviss EA. A systematic review of the diagnostic accuracy of physical examination for the detection of cirrhosis. BMC Med Inform Decis Mak. 2001;1:6.
PubMed Abstract»
Dickson G. Gynecomastia. Am Fam Physician. 2012;85:716-22.
PubMed Abstract»
Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation. Am Fam Physician. 2006;74:756-62.
PubMed Abstract»
Holzberg M, Walker HK. Terry's nails: revised definition and new correlations. Lancet. 1984;1:896-9.
PubMed Abstract»
Khasnis A, Gokula RM. Spider nevus. J Postgrad Med. 2002;48:307-9.
PubMed Abstract»
Kim Sh, Keum B, Kim E, Jeen Y, Chun H. Hepatobiliary and pancreatic: Caput medusae. J Gastroenterol Hepatol. 2014;29:1952.
PubMed Abstract»
Li CP, Lee FY, Hwang SJ, et al. Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. World J Gastroenterol. 2003;9:2832-5.
PubMed Abstract»
McGee S. Simplifying likelihood ratios. J Gen Intern Med. 2002;17:646-9.
PubMed Abstract»
Pitukweerakul S, Pilla S. Terry's Nails and Lindsay's Nails: Two Nail Abnormalities in Chronic Systemic Diseases. J Gen Intern Med. 2016;31:970.
PubMed Abstract»
Ruiz MA, Saab S, Rickman LS. The clinical detection of scleral icterus: observations of multiple examiners. Mil Med. 1997;162:560-3.
PubMed Abstract»
Satapathy SK, Bernstein D. Dermatologic disorders and the liver. Clin Liver Dis. 2011;15:165-82.
PubMed Abstract»
Serrao R, Zirwas M, English JC. Palmar erythema. Am J Clin Dermatol. 2007;8:347-56.
PubMed Abstract»
Udell JA, Wang CS, Tinmouth J, et al. Does this patient with liver disease have cirrhosis? JAMA. 2012;307:832-42.
PubMed Abstract»
Yang PM, Chen DS. Images in clinical medicine. Caput medusae. N Engl J Med. 2005;353:e19.
PubMed Abstract»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Initial Laboratory Evaluation

Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
PubMed Abstract»
Rotman Y, Brown TA, Hoofnagle JH. Evaluation of the patient with hepatitis B. Hepatology. 2009;49:S22-7.
PubMed Abstract»
Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922-65.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Screening for Other Causes of Liver Disease

Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:328-43.
PubMed Abstract»
Batts KP. Iron overload syndromes and the liver. Mod Pathol. 2007;20 Suppl 1:S31-9.
PubMed Abstract»
Brandhagen DJ, Fairbanks VF, Baldus W. Recognition and management of hereditary hemochromatosis. Am Fam Physician. 2002;65:853-60.
PubMed Abstract»
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142:1592-609.
PubMed Abstract»
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328-57.
PubMed Abstract»
Cohen JA, Kaplan MM. The SGOT/SGPT ratio--an indicator of alcoholic liver disease. Dig Dis Sci. 1979;24:835-8.
PubMed Abstract»
Czaja AJ, Freese DK. Diagnosis and treatment of autoimmune hepatitis. Hepatology. 2002;36:479-97.
PubMed Abstract»
Diehl AM, Day C. Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis. N Engl J Med. 2017;377:2063-72.
PubMed Abstract»
Donato F, Tagger A, Gelatti U, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155:323-31.
PubMed Abstract»
Dugum M, McCullough A. Diagnosis and Management of Alcoholic Liver Disease. J Clin Transl Hepatol. 2015;3:109-16.
PubMed Abstract»
Eddowes PJ, Sasso M, Allison M, et al. Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019;156:1717-1730.
PubMed Abstract»
Fleming RE, Ponka P. Iron overload in human disease. N Engl J Med. 2012;366:348-59.
PubMed Abstract»
Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008;48:169-76.
PubMed Abstract»
Iida-Ueno A, Enomoto M, Tamori A, Kawada N. Hepatitis B virus infection and alcohol consumption. World J Gastroenterol. 2017;23:2651-9.
PubMed Abstract»
Ikeda K, Saitoh S, Suzuki Y, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients. J Hepatol. 1998;28:930-8.
PubMed Abstract»
Kowdley KV. Iron Overload in Patients With Chronic Liver Disease. Gastroenterol Hepatol (N Y). 2016;12:695-8.
PubMed Abstract»
Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006;354:54-66.
PubMed Abstract»
Lin CW, Lin CC, Mo LR, et al. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol. 2013;58:730-5.
PubMed Abstract»
Lucey MR, Mathurin P, Morgan TR. Alcoholic hepatitis. N Engl J Med. 2009;360:2758-69.
PubMed Abstract»
Mack CL, Adams D, Assis DN, et al. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology. 2020;72:671-722.
PubMed Abstract»
Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:2193-213.
PubMed Abstract»
Manns MP, Lohse AW, Vergani D. Autoimmune hepatitis--Update 2015. J Hepatol. 2015;62:S100-11.
PubMed Abstract»
Marciniak SJ, Lomas DA. Alpha1-antitrypsin deficiency and autophagy. N Engl J Med. 2010;363:1863-4.
PubMed Abstract»
Mieli-Vergani G, Vergani D, Czaja AJ, et al. Autoimmune hepatitis. Nat Rev Dis Primers. 2018;4:18017.
PubMed Abstract»
Nelson DR, Teckman J, Di Bisceglie AM, Brenner DA. Diagnosis and management of patients with α1-antitrypsin (A1AT) deficiency. Clin Gastroenterol Hepatol. 2012;10:575-80.
PubMed Abstract»
Qaseem A, Aronson M, Fitterman N, Snow V, Weiss KB, Owens DK. Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2005;143:517-21.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schmitt B, Golub RM, Green R. Screening primary care patients for hereditary hemochromatosis with transferrin saturation and serum ferritin level: systematic review for the American College of Physicians. Ann Intern Med. 2005;143:522-36.
PubMed Abstract»
Singal AK, Bataller R, Ahn J, Kamath PS, Shah VH. ACG Clinical Guideline: Alcoholic Liver Disease. Am J Gastroenterol. 2018;113:175-194.
PubMed Abstract»
Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet. 2005;365:2225-36.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Tome S, Lucey MR. Review article: current management of alcoholic liver disease. Aliment Pharmacol Ther. 2004;19:707-14.
PubMed Abstract»
Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15:11-20.
PubMed Abstract»
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73-84.
PubMed Abstract»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Evaluation of Fibrosis Stage

Castera L. Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology. 2012;142:1293-1302.e4.
PubMed Abstract»
Theise ND. Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach. Mod Pathol. 2007;20 Suppl 1:S3-14.
PubMed Abstract»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Immunizations for Persons with Chronic HBV and Cirrhosis

Advisory Committee on Immunization Practices (ACIP). Adult Immunization Schedule: Recommended Immunization Schedule for Ages 19 Years or Older, United States, 2022.
ACIP»
Advisory Committee on Immunization Practices (ACIP). Recommended Adult Immunization Schedule by Medical Condition and Other Indications, United States, 2020.
ACIP»
Advisory Committee on Immunization Practices (ACIP). Recommended Adult Immunization Schedule by Medical Condition and Other Indications, United States, 2022.
ACIP»
Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61:816-9.
PubMed Abstract»
Centers for Disease Control and Prevention. Vaccine information for adults: liver disease and adult vaccination.
CDC»
Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55:1-23.
PubMed Abstract»
Kobayashi M, Farrar JL, Gierke R, et al. Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:109-17.
PubMed Abstract»
Matanock A, Lee G, Gierke R, Kobayashi M, Leidner A, Pilishvili T. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:1069-75.
PubMed Abstract»
Nelson NP, Weng MK, Hofmeister MG, et al. Prevention of Hepatitis A Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020. MMWR Recomm Rep. 2020;69:1-38.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Win NN, Kanda T, Ogawa M, et al. Superinfection of hepatitis A virus in hepatocytes infected with hepatitis B virus. Int J Med Sci. 2019;16:1366-70.
PubMed Abstract»
Module 3 » Lesson 3. Initial Evaluation of Persons with Chronic Hepatitis B

Counseling Persons with Chronic HBV Following Diagnosis

Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Lai CL, Dienstag J, Schiff E, et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis. 2003;36:687-96.
PubMed Abstract»
Mushahwar IK, Dienstag JL, Polesky HF, McGrath LC, Decker RH, Overby LR. Interpretation of various serological profiles of hepatitis B virus infection. Am J Clin Pathol. 1981;76:773-7.
PubMed Abstract»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44-100.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546-55.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014;384:2053-63.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»

Lesson 4. Natural History of Chronic HBV

Module 3 » Lesson 4. Natural History of Chronic HBV

Classification and Phases of Chronic HBV Infection

Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45:1056-75.
PubMed Abstract»
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. American Association for the Study of Liver Diseases Practice Guidelines.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
Sorrell MF, Belongia EA, Costa J, et al. National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med. 2009;150:104-10.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Module 3 » Lesson 4. Natural History of Chronic HBV

Natural History and Phases of Chronic HBV

Hayashi K, Ishigami M, Ishizu Y, et al. Clinical characteristics and molecular analysis of hepatitis B virus reactivation in hepatitis B surface antigen-negative patients during or after immunosuppressive or cytotoxic chemotherapy. J Gastroenterol. 2016;51:1081-1089.
PubMed Abstract»
Mastroianni CM, Lichtner M, Citton R, et al. Current trends in management of hepatitis B virus reactivation in the biologic therapy era. World J Gastroenterol. 2011;17:3881-7.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
Nard FD, Todoerti M, Grosso V, et al. Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs. World J Hepatol. 2015;7:344-61.
PubMed Abstract»
Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001;120:1009-22.
PubMed Abstract»
Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5:215-29.
PubMed Abstract»
Module 3 » Lesson 4. Natural History of Chronic HBV

Immune-Tolerant Chronic HBV Infection

Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med. 2001;135:759-68.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Module 3 » Lesson 4. Natural History of Chronic HBV

Immune-Active Chronic HBV Infection

Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med. 2001;135:759-68.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Module 3 » Lesson 4. Natural History of Chronic HBV

Inactive Chronic HBV Infection

Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.
PubMed Abstract»
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
Spradling PR, Bulkow L, Teshale EH, et al. Prevalence and causes of elevated serum aminotransferase levels in a population-based cohort of persons with chronic hepatitis B virus infection. J Hepatol. 2014;61:785-91.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Villa E, Fattovich G, Mauro A, Pasino M. Natural history of chronic HBV infection: special emphasis on the prognostic implications of the inactive carrier state versus chronic hepatitis. Dig Liver Dis. 2011;43 Suppl 1:S8-14.
PubMed Abstract»
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301-1314.
PubMed Abstract»
Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358-80.
PubMed Abstract»
Hoofnagle JH, Doo E, Liang TJ, Fleischer R, Lok AS. Management of hepatitis B: summary of a clinical research workshop. Hepatology. 2007;45:1056-75.
PubMed Abstract»
Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315-41.
PubMed Abstract»
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-39.
PubMed Abstract»
McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381-96.
PubMed Abstract»
Sorrell MF, Belongia EA, Costa J, et al. National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med. 2009;150:104-10.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Villa E, Fattovich G, Mauro A, Pasino M. Natural history of chronic HBV infection: special emphasis on the prognostic implications of the inactive carrier state versus chronic hepatitis. Dig Liver Dis. 2011;43 Suppl 1:S8-14.
PubMed Abstract»

Module 3. Prevention of HBV

Lesson 1. HBV Immunizations

Module 3 » Lesson 1. HBV Immunizations

Background

André FE. Summary of safety and efficacy data on a yeast-derived hepatitis B vaccine. Am J Med. 1989;87:14S-20S.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Murphy TV, Fenlon N, Ko S, Ward JW. Update: Shortened Interval for Postvaccination Serologic Testing of Infants Born to Hepatitis B-Infected Mothers. MMWR Morb Mortal Wkly Rep. 2015;64:1118-20.
PubMed Abstract»
Stephenne J. Development and production aspects of a recombinant yeast-derived hepatitis B vaccine. Vaccine. 1990;8 Suppl:S69-73; discussion S79-80.
PubMed Abstract»
Szmuness W, Stevens CE, Harley EJ, et al. Hepatitis B vaccine: demonstration of efficacy in a controlled clinical trial in a high-risk population in the United States. N Engl J Med. 1980;303:833-41.
PubMed Abstract»
Vesikari T, Langley JM, Segall N, et al. Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2021;21:1271-81.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
World Health Organization. Global Hepatitis Report 2017. Geneva: World Health Organization; April, 2017:1-83.
WHO»
Young MD, Schneider DL, Zuckerman AJ, Du W, Dickson B, Maddrey WC. Adult hepatitis B vaccination using a novel triple antigen recombinant vaccine. Hepatology. 2001;34:372-6.
PubMed Abstract»
Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine. 2008;26:6266-73.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

Vaccine Uptake

Centers for Disease Control and Prevention (CDC). Hepatitis B vaccination among high-risk adolescents and adults--San Diego, California, 1998-2001. MMWR Morb Mortal Wkly Rep. 2002;51:618-21.
PubMed Abstract»
Daley MF, Hennessey KA, Weinbaum CM, et al. Physician practices regarding adult hepatitis B vaccination: a national survey. Am J Prev Med. 2009;36:491-6.
PubMed Abstract»
Daniels D, Grytdal S, Wasley A; Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis - United States, 2007. MMWR Surveill Summ. 2009;58:1-27.
PubMed Abstract»
Lu PJ, Hung MC, Srivastav A, et al. Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018. MMWR Surveill Summ. 2021;70:1-26.
PubMed Abstract»
Weinbaum CM, Lyerla R, Mackellar DA, et al. The Young Men's Survey phase II: hepatitis B immunization and infection among young men who have sex with men. Am J Public Health. 2008;98:839-45.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

Indications for Hepatitis B Vaccination

Bradley H, Hall E, Asher A, et al. Estimated number of people who inject drugs in the United States. Clin Infect Dis. 2022 Jul 6. Online ahead of print.
PubMed Abstract»
Centers for Disease Control (CDC). Recommendation of the Immunization Practices Advisory Committee (ACIP). Inactivated hepatitis B virus vaccine. MMWR Morb Mortal Wkly Rep. 1982;31:317-22, 327-8.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Centers for Disease Control and Prevention (CDC).. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60:1709-11.
PubMed Abstract»
Iqbal K, Klevens RM, Kainer MA, et al. Epidemiology of Acute Hepatitis B in the United States From Population-Based Surveillance, 2006-2011. Clin Infect Dis. 2015;61:584-92.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

Prevaccination Serologic Testing

Blostein J, Clark PA. Cost-effectiveness of preimmunization hepatitis B screening in high-risk adolescents. Public Health Rep. 2001;116:165-8.
PubMed Abstract»
Centers for Disease Control and Prevention. Hepatitis B vaccination of inmates in correctional facilities--Texas, 2000-2002. MMWR Morb Mortal Wkly Rep. 2004;53:681-3.
PubMed Abstract»
Hu Y, Grau LE, Scott G, et al. Economic evaluation of delivering hepatitis B vaccine to injection drug users. Am J Prev Med. 2008;35:25-32.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30:2212-9.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546-55.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

HBV Vaccines and Schedules

Awad AM, Ntoso A, Connaire JJ, et al. An open-label, single-arm study evaluating the immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) in adults receiving hemodialysis. Vaccine. 2021;39:3346-52.
PubMed Abstract»
Centers for Disease Control and Prevention. Guidelines for Vaccinating Kidney Dialysis Patients and Patients with Chronic Kidney Disease. December 2012.
CDC»
Janssen RS, Mangoo-Karim R, Pergola PE, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease. Vaccine. 2013;31:5306-13.
PubMed Abstract»
Lee JH, Hong S, Im JH, Lee JS, Baek JH, Kwon HY. Systematic review and meta-analysis of immune response of double dose of hepatitis B vaccination in HIV-infected patients. Vaccine. 2020;38:3995-4000.
PubMed Abstract»
Liang JL, Tiwari T, Moro P, et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine. 1989;7:425-30.
PubMed Abstract»
Tung J, Carlisle E, Smieja M, Kim PT, Lee CH. A randomized clinical trial of immunization with combined hepatitis A and B versus hepatitis B alone for hepatitis B seroprotection in hemodialysis patients. Am J Kidney Dis. 2010;56:713-9.
PubMed Abstract»
Vesikari T, Finn A, van Damme P, et al. Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2021;4:e2128652.
PubMed Abstract»
Vesikari T, Langley JM, Segall N, et al. Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2021;21:1271-81.
PubMed Abstract»
Weber DJ, Rutala WA, Samsa GP, Santimaw JE, Lemon SM. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA. 1985;254:3187-9.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

Response to HBV Vaccines

Alper CA, Kruskall MS, Marcus-Bagley D, et al. Genetic prediction of nonresponse to hepatitis B vaccine. N Engl J Med. 1989;321:708-12.
PubMed Abstract»
André FE. Summary of safety and efficacy data on a yeast-derived hepatitis B vaccine. Am J Med. 1989;87:14S-20S.
PubMed Abstract»
Averhoff F, Mahoney F, Coleman P, Schatz G, Hurwitz E, Margolis H. Immunogenicity of hepatitis B Vaccines. Implications for persons at occupational risk of hepatitis B virus infection. Am J Prev Med. 1998;15:1-8.
PubMed Abstract»
Bauer T, Jilg W. Hepatitis B surface antigen-specific T and B cell memory in individuals who had lost protective antibodies after hepatitis B vaccination. Vaccine. 2006;24:572-7.
PubMed Abstract»
Bruce MG, Bruden D, Hurlburt D, et al. Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. J Infect Dis. 2016;214:16-22.
PubMed Abstract»
Bruce MG, Bruden D, Hurlburt D, et al. Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose. Hepatology. 2022 Mar 23. Online ahead of print.
PubMed Abstract»
Bruguera M, Cremades M, Salinas R, Costa J, Grau M, Sans J. Impaired response to recombinant hepatitis B vaccine in HIV-infected persons. J Clin Gastroenterol. 1992;14:27-30.
PubMed Abstract»
Collier AC, Corey L, Murphy VL, Handsfield HH. Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination. Ann Intern Med. 1988;109:101-5.
PubMed Abstract»
Degos F, Duhamel G, Brechot C, et al. Hepatitis B vaccination in chronic alcoholics. J Hepatol. 1986;2:402-9.
PubMed Abstract»
Fitzsimons D, François G, Hall A, et al. Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants. Vaccine. 2005;23:4158-66.
PubMed Abstract»
Fonseca MO, Pang LW, de Paula Cavalheiro N, Barone AA, Heloisa Lopes M. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. Vaccine. 2005;23:2902-8.
PubMed Abstract»
Gara N, Abdalla A, Rivera E, et al. Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults. Clin Infect Dis. 2015;60:505-13.
PubMed Abstract»
Halperin SA, Dobson S, McNeil S, et al. Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults. Vaccine. 2006;24:20-6.
PubMed Abstract»
Halperin SA, Ward B, Cooper C, et al. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine. 2012;30:2556-63.
PubMed Abstract»
Heyward WL, Kyle M, Blumenau J, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed hepatitis B vaccine in healthy adults 40-70 years of age. Vaccine. 2013;31:5300-5.
PubMed Abstract»
Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36:668-674.
PubMed Abstract»
Janssen RS, Mangoo-Karim R, Pergola PE, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease. Vaccine. 2013;31:5306-13.
PubMed Abstract»
Joines RW, Blatter M, Abraham B, et al. A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (Twinrix) with corresponding monovalent vaccines (Havrix and Engerix-B) in adults. Vaccine. 2001;19:4710-9.
PubMed Abstract»
Lacson E, Teng M, Ong J, Vienneau L, Ofsthun N, Lazarus JM. Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease. Hemodial Int. 2005;9:367-75.
PubMed Abstract»
Langö-Warensjö A, Cardell K, Lindblom B. Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen. Tissue Antigens. 1998;52:374-80.
PubMed Abstract»
Lin YC, Chang MH, Ni YH, Hsu HY, Chen DS. Long-term immunogenicity and efficacy of universal hepatitis B virus vaccination in Taiwan. J Infect Dis. 2002;187:134-8.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Mendenhall C, Roselle GA, Lybecker LA, et al. Hepatitis B vaccination. Response of alcoholic with and without liver injury. Dig Dis Sci. 1988;33:263-9.
PubMed Abstract»
Middleman AB, Baker CJ, Kozinetz CA, et al. Duration of protection after infant hepatitis B vaccination series. Pediatrics. 2014;133:e1500-7.
PubMed Abstract»
Propst T, Propst A, Lhotta K, Vogel W, König P. Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination. Am J Kidney Dis. 1998;32:1041-5.
PubMed Abstract»
Sablan BP, Kim DJ, Barzaga NG, et al. Demonstration of safety and enhanced seroprotection against hepatitis B with investigational HBsAg-1018 ISS vaccine compared to a licensed hepatitis B vaccine. Vaccine. 2012;30:2689-96.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine. 1989;7:425-30.
PubMed Abstract»
Vesikari T, Langley JM, Segall N, et al. Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2021;21:1271-81.
PubMed Abstract»
Williams IT, Goldstein ST, Tufa J, Tauillii S, Margolis HS, Mahoney FJ. Long term antibody response to hepatitis B vaccination beginning at birth and to subsequent booster vaccination. Pediatr Infect Dis J. 2003;22:157-63.
PubMed Abstract»
Zajac BA, West DJ, McAleer WJ, Scolnick EM. Overview of clinical studies with hepatitis B vaccine made by recombinant DNA. J Infect. 1986;13 Suppl A:39-45.
PubMed Abstract»
Zanetti AR, Mariano A, Romanò L, et al. Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study. Lancet. 2005;366:1379-84.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

Postvaccination Serologic Testing

Challapalli M, Naidu V, Cunningham DG. Hepatitis B surface antigenemia in a newborn infant after vaccination. Pediatr Infect Dis J. 1993;12:408-9.
PubMed Abstract»
Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18:52-61.
PubMed Abstract»
Fleischer L, Syed SS. Hepatitis B surface antigenemia in a neonate following vaccination with Pediarix. Clin Pediatr (Phila). 2009;48:311-2.
PubMed Abstract»
Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med. 1986;315:209-14.
PubMed Abstract»
Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Onuigbo MA, Nesbit A, Weisenbeck J, Hurlburt J. Hepatitis B surface antigenemia following recombinant Engerix B hepatitis B vaccine in an 81-year-old ESRD patient on hemodialysis. Ren Fail. 2010;32:531-2.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Murphy TV, Fenlon N, Ko S, Ward JW. Update: Shortened Interval for Postvaccination Serologic Testing of Infants Born to Hepatitis B-Infected Mothers. MMWR Morb Mortal Wkly Rep. 2015;64:1118-20.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Module 3 » Lesson 1. HBV Immunizations

Management of HBV Vaccine Nonresponders

Alper CA, Kruskall MS, Marcus-Bagley D, et al. Genetic prediction of nonresponse to hepatitis B vaccine. N Engl J Med. 1989;321:708-12.
PubMed Abstract»
Barraclough KA, Wiggins KJ, Hawley CM, et al. Intradermal versus intramuscular hepatitis B vaccination in hemodialysis patients: a prospective open-label randomized controlled trial in nonresponders to primary vaccination. Am J Kidney Dis. 2009;54:95-103.
PubMed Abstract»
Bertino JS Jr, Tirrell P, Greenberg RN, et al. A comparative trial of standard or high-dose S subunit recombinant hepatitis B vaccine versus a vaccine containing S subunit, pre-S1, and pre-S2 particles for revaccination of healthy adult nonresponders. J Infect Dis. 1997;175:678-81.
PubMed Abstract»
Cardell K, Akerlind B, Sällberg M, Frydén A. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine. J Infect Dis. 2008;198:299-304.
PubMed Abstract»
Centers for Disease Control and Prevention. Guidelines for Vaccinating Kidney Dialysis Patients and Patients with Chronic Kidney Disease. December 2012.
CDC»
Clemens R, Sänger R, Kruppenbacher J, et al. Booster immunization of low- and non-responders after a standard three dose hepatitis B vaccine schedule--results of a post-marketing surveillance. Vaccine. 1997;15:349-52.
PubMed Abstract»
David MC, Ha SH, Paynter S, Lau C. A systematic review and meta-analysis of management options for adults who respond poorly to hepatitis B vaccination. Vaccine. 2015;33:6564-9.
PubMed Abstract»
Dhillon S, Moore C, Li SD, et al. Efficacy of high-dose intra-dermal hepatitis B virus vaccine in previous vaccination non-responders with chronic liver disease. Dig Dis Sci. 2012;57:215-20.
PubMed Abstract»
Fabrizi F, Andrulli S, Bacchini G, Corti M, Locatelli F. Intradermal versus intramuscular hepatitis b re-vaccination in non-responsive chronic dialysis patients: a prospective randomized study with cost-effectiveness evaluation. Nephrol Dial Transplant. 1997;12:1204-11.
PubMed Abstract»
Goldwater PN. Randomized, comparative trial of 20 micrograms vs 40 micrograms Engerix B vaccine in hepatitis B vaccine non-responders. Vaccine. 1997;15:353-6.
PubMed Abstract»
Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med. 1986;315:209-14.
PubMed Abstract»
Halperin SA, Ward BJ, Dionne M, et al. Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine. Hum Vaccin Immunother. 2013;9:1438-44.
PubMed Abstract»
Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36:668-674.
PubMed Abstract»
Janssen RS, Mangoo-Karim R, Pergola PE, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease. Vaccine. 2013;31:5306-13.
PubMed Abstract»
Joukar F, Mansour-Ghanaei F, Naghipour MR, Asgharnezhad M. Immune Responses to Single-Dose Versus Double-Dose Hepatitis B Vaccines in Healthcare Workers not Responding to the Primary Vaccine Series: A Randomized Clinical Trial. Hepat Mon. 2016;16:e32799.
PubMed Abstract»
Kim HN, Harrington RD, Crane HM, Dhanireddy S, Dellit TH, Spach DH. Hepatitis B vaccination in HIV-infected adults: current evidence, recommendations and practical considerations. Int J STD AIDS. 2009;20:595-600.
PubMed Abstract»
Kim MJ, Nafziger AN, Harro CD, et al. Revaccination of healthy nonresponders with hepatitis B vaccine and prediction of seroprotection response. Vaccine. 2003;21:1174-9.
PubMed Abstract»
Langö-Warensjö A, Cardell K, Lindblom B. Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen. Tissue Antigens. 1998;52:374-80.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Noh KW, Poland GA, Murray JA. Hepatitis B vaccine nonresponse and celiac disease. Am J Gastroenterol. 2003;98:2289-92.
PubMed Abstract»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Park SD, Markowitz J, Pettei M, et al. Failure to respond to hepatitis B vaccine in children with celiac disease. J Pediatr Gastroenterol Nutr. 2007;44:431-5.
PubMed Abstract»
Peces R, de la Torre M, Alcázar R, Urra JM. Prospective analysis of the factors influencing the antibody response to hepatitis B vaccine in hemodialysis patients. Am J Kidney Dis. 1997;29:239-45.
PubMed Abstract»
Propst T, Propst A, Lhotta K, Vogel W, König P. Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination. Am J Kidney Dis. 1998;32:1041-5.
PubMed Abstract»
Sablan BP, Kim DJ, Barzaga NG, et al. Demonstration of safety and enhanced seroprotection against hepatitis B with investigational HBsAg-1018 ISS vaccine compared to a licensed hepatitis B vaccine. Vaccine. 2012;30:2689-96.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Shafran SD, Mashinter LD, Lindemulder A, Taylor GD, Chiu I. Poor efficacy of intradermal administration of recombinant hepatitis B virus immunization in HIV-infected individuals who fail to respond to intramuscular administration of hepatitis B virus vaccine. HIV Med. 2007;8:295-9.
PubMed Abstract»
Shapira MY, Zeira E, Adler R, Shouval D. Rapid seroprotection against hepatitis B following the first dose of a Pre-S1/Pre-S2/S vaccine. J Hepatol. 2001;34:123-7.
PubMed Abstract»
Suzuki H, Iino S, Shiraki K, et al. Safety and efficacy of a recombinant yeast-derived pre-S2 + S-containing hepatitis B vaccine (TGP-943): phase 1, 2 and 3 clinical testing. Vaccine. 1994;12:1090-6.
PubMed Abstract»
van den Berg R, van Hoogstraten I, van Agtmael M. Non-responsiveness to hepatitis B vaccination in HIV seropositive patients; possible causes and solutions. AIDS Rev. 2009;11:157-64.
PubMed Abstract»
Yap I, Guan R, Chan SH. Study on the comparative immunogenicity of a recombinant DNA hepatitis B vaccine containing pre-S components of the HBV coat protein with non pre-S containing vaccines. J Gastroenterol Hepatol. 1995;10:51-5.
PubMed Abstract»
Yu AS, Cheung RC, Keeffe EB. Hepatitis B vaccines. Clin Liver Dis. 2004;8:283-300.
PubMed Abstract»
Zuckerman JN, Sabin C, Craig FM, Williams A, Zuckerman AJ. Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study. BMJ. 1997;314:329-33.
PubMed Abstract»

Additional References

A Two-Dose Hepatitis B Vaccine for Adults (Heplisav-B). JAMA. 2018;319:822-3.
PubMed Abstract»
Akcay IM, Katrinli S, Ozdil K, Doganay GD, Doganay L. Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies. World J Gastroenterol. 2018;24:3347-3360.
PubMed Abstract»
Barry M, Cooper C. Review of hepatitis B surface antigen-1018 ISS adjuvant-containing vaccine safety and efficacy. Expert Opin Biol Ther. 2007;7:1731-7.
PubMed Abstract»
Bruce MG, Bruden D, Hurlburt D, et al. Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. J Infect Dis. 2016;214:16-22.
PubMed Abstract»
Bruce MG, Bruden D, Hurlburt D, et al. Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose. Hepatology. 2022;76:1180-9.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Chaiklang K, Wipasa J, Chaiwarith R, Praparattanapan J, Supparatpinyo K. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial. PLoS One. 2013;8:e80409.
PubMed Abstract»
Choudhury SA, Peters VB. Responses to hepatitis B vaccine boosters in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 1995;14:65-7.
PubMed Abstract»
Conners EE, Panagiotakopoulos L, Hofmeister MG, et al. Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023. MMWR Recomm Rep. 2023;72:1-25.
PubMed Abstract»
Elhanan E, Boaz M, Schwartz I, et al. A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients. Clin Exp Nephrol. 2018;22:151-158.
PubMed Abstract»
Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial. 2005;18:52-61.
PubMed Abstract»
Haber P, Moro PL, Ng C, et al. Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015. Vaccine. 2018;36:559-564.
PubMed Abstract»
Hadler SC, Francis DP, Maynard JE, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in homosexual men. N Engl J Med. 1986;315:209-14.
PubMed Abstract»
Hill HA, Elam-Evans LD, Yankey D, Singleton JA, Kang Y. Vaccination Coverage Among Children Aged 19-35 Months - United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67:1123-8.
PubMed Abstract»
Hyer R, McGuire DK, Xing B, Jackson S, Janssen R. Safety of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant in adults. Vaccine. 2018;36:2604-2611.
PubMed Abstract»
Iqbal K, Klevens RM, Kainer MA, et al. Epidemiology of Acute Hepatitis B in the United States From Population-Based Surveillance, 2006-2011. Clin Infect Dis. 2015;61:584-92.
PubMed Abstract»
Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Janssen JM, Heyward WL, Martin JT, Janssen RS. Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus. Vaccine. 2015;33:833-7.
PubMed Abstract»
Ko SC, Schillie SF, Walker T, et al. Hepatitis B vaccine response among infants born to hepatitis B surface antigen-positive women. Vaccine. 2014;32:2127-33.
PubMed Abstract»
Krawczyk A, Ludwig C, Jochum C, et al. Induction of a robust T- and B-cell immune response in non- and low-responders to conventional vaccination against hepatitis B by using a third generation PreS/S vaccine. Vaccine. 2014;32:5077-82.
PubMed Abstract»
Launay O, van der Vliet D, Rosenberg AR, et al. Safety and immunogenicity of 4 intramuscular double doses and 4 intradermal low doses vs standard hepatitis B vaccine regimen in adults with HIV-1: a randomized controlled trial. JAMA. 2011;305:1432-40.
PubMed Abstract»
Lemon SM, Thomas DL. Vaccines to prevent viral hepatitis. N Engl J Med. 1997;336:196-204.
PubMed Abstract»
Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis. 2011;53:68-75.
PubMed Abstract»
Lu PJ, O'Halloran A, Kennedy ED, et al. Awareness among adults of vaccine-preventable diseases and recommended vaccinations, United States, 2015. Vaccine. 2017;35:3104-3115.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30:2212-9.
PubMed Abstract»
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Hepatitis B virus infection. Last Updated: September 7, 2022.
HIV.gov»
Poland GA, Jacobson RM. Clinical practice: prevention of hepatitis B with the hepatitis B vaccine. N Engl J Med. 2004;351:2832-8.
PubMed Abstract»
Rey D, Krantz V, Partisani M, et al. Increasing the number of hepatitis B vaccine injections augments anti-HBs response rate in HIV-infected patients. Effects on HIV-1 viral load. Vaccine. 2000;18:1161-5.
PubMed Abstract»
Rey D, Piroth L, Wendling MJ, et al. Safety and immunogenicity of double-dose versus standard-dose hepatitis B revaccination in non-responding adults with HIV-1 (ANRS HB04 B-BOOST): a multicentre, open-label, randomised controlled trial. Lancet Infect Dis. 2015;15:1283-91.
PubMed Abstract»
Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44-100.
PubMed Abstract»
Saco TV, Strauss AT, Ledford DK. Hepatitis B vaccine nonresponders: Possible mechanisms and solutions. Ann Allergy Asthma Immunol. 2018;121:320-327.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546-55.
PubMed Abstract»
Splawn LM, Bailey CA, Medina JP, Cho JC. Heplisav-B vaccination for the prevention of hepatitis B virus infection in adults in the United States. Drugs Today (Barc). 2018;54:399-405.
PubMed Abstract»
Strikas RA. Advisory committee on immunization practices recommended immunization schedules for persons aged 0 through 18 years--United States, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:93-4.
PubMed Abstract»
Tong NK, Beran J, Kee SA, et al. Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients. Kidney Int. 2005;68:2298-303.
PubMed Abstract»
van Bömmel F, Berg T. Three are better than one-increasing HBV seroprotection by a tri-antigenic vaccine. Lancet Infect Dis. 2021;21:1197-8.
PubMed Abstract»
Van Den Ende C, Marano C, Van Ahee A, Bunge EM, De Moerlooze L. The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience. Expert Rev Vaccines. 2017;16:811-32.
PubMed Abstract»
Walayat S, Ahmed Z, Martin D, Puli S, Cashman M, Dhillon S. Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine. World J Hepatol. 2015;7:2503-9.
PubMed Abstract»
Walker TY, Elam-Evans LD, Yankey D, et al. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67:909-917.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Wiedmann M, Liebert UG, Oesen U, et al. Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C. Hepatology. 2000;31:230-4.
PubMed Abstract»
World Health Organization. Global Hepatitis Report 2017. Geneva: World Health Organization; April, 2017:1-83.
WHO»
Yousaf F, Gandham S, Galler M, Spinowitz B, Charytan C. Systematic review of the efficacy and safety of intradermal versus intramuscular hepatitis B vaccination in end-stage renal disease population unresponsive to primary vaccination series. Ren Fail. 2015;37:1080-8.
PubMed Abstract»

Lesson 2. Preventing HBV Perinatal Transmission

Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Universal Screening for HBV Infection During Pregnancy

Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63:319-33.
PubMed Abstract»
Freedman M, Kroger A, Hunter P, Ault KA. Recommended Adult Immunization Schedule, United States, 2020. Ann Intern Med. 2020 Feb 4. [Epub ahead of print]
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Risk of Perinatal HBV Transmission

Beasley RP, Hwang LY, Lee GC, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;2:1099-102.
PubMed Abstract»
Burk RD, Hwang LY, Ho GY, Shafritz DA, Beasley RP. Outcome of perinatal hepatitis B virus exposure is dependent on maternal virus load. J Infect Dis. 1994;170:1418-23.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Centers for Disease Control and Prevention (CDC). Clinical Overview of Perinatal Hepatitis B.Infection Rates and Trends.
CDC»
Committee on Infectious Diseases; Committee on Fetus and Newborn. Elimination of Perinatal Hepatitis B: Providing the First Vaccine Dose Within 24 Hours of Birth. Pediatrics. 2017;140.pii: e20171870.
PubMed Abstract»
Ko SC, Fan L, Smith EA, Fenlon N, Koneru AK, Murphy TV. Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000-2009. J Pediatric Infect Dis Soc. 2016;5:114-21.
PubMed Abstract»
Koneru A, Schillie S, Roberts H, et al. Estimating Annual Births to Hepatitis B Surface Antigen-Positive Women in the United States by Using Data on Maternal Country of Birth. Public Health Rep. 2019;134:255-63.
PubMed Abstract»
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev. 2006;:CD004790.
PubMed Abstract»
Lu Y, Song Y, Zhai X, et al. Maternal hepatitis B e antigen can be an indicator for antiviral prophylaxis of perinatal transmission of hepatitis B virus. Emerg Microbes Infect. 2021;10:555-564.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
National Center for HIV, Viral Hepatitis, STD, and TB Prevention. Pregnancy and HIV, Viral Hepatitis, STD & TB Prevention: HBV Infection.
CDC»
Salemi JL, Spooner KK, Mejia de Grubb MC, Aggarwal A, Matas JL, Salihu HM. National trends of hepatitis B and C during pregnancy across sociodemographic, behavioral, and clinical factors, United States, 1998-2011. J Med Virol. 2017;89:1025-32.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Silverman NS. Hepatitis B Screening in Pregnant Women: A Perspective on the New USPSTF Recommendations. JAMA. 2019;322:312-4.
PubMed Abstract»
Stevens CE, Taylor PE, Tong MJ, et al. Yeast-recombinant hepatitis B vaccine. Efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission. JAMA. 1987;257:2612-6.
PubMed Abstract»
Stevens CE, Toy PT, Tong MJ, et al. Perinatal hepatitis B virus transmission in the United States. Prevention by passive-active immunization. JAMA. 1985;253:1740-5.
PubMed Abstract»
US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
Xu ZY, Liu CB, Francis DP, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial. Pediatrics. 1985;76:713-8.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Route and Timing of Perinatal HBV Transmission

Alexander JM, Ramus R, Jackson G, Sercely B, Wendel GD Jr. Risk of hepatitis B transmission after amniocentesis in chronic hepatitis B carriers. Infect Dis Obstet Gynecol. 1999;7:283-6.
PubMed Abstract»
Bai X, Yang H, Wan L, et al. Involvement of viperin in prevention of intrauterine transmission of hepatitis B virus. APMIS. 2017;125:170-5.
PubMed Abstract»
Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. Lancet. 1975;2:740-1.
PubMed Abstract»
Chen LZ, Zhou WQ, Zhao SS, Liu ZY, Wen SW. A nested case-control study of maternal-neonatal transmission of hepatitis B virus in a Chinese population. World J Gastroenterol. 2011;17:3640-4.
PubMed Abstract»
Ghaffar YA, elSobky MK, Raouf AA, Dorgham LS. Mother-to-child transmission of hepatitis B virus in a semirural population in Egypt. J Trop Med Hyg. 1989;92:20-6.
PubMed Abstract»
Giles ML, Visvanathan K, Lewin SR, Sasadeusz J. Chronic hepatitis B infection and pregnancy. Obstet Gynecol Surv. 2012;67:37-44.
PubMed Abstract»
Hill JB, Sheffield JS, Kim MJ, Alexander JM, Sercely B, Wendel GD. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol. 2002;99:1049-52.
PubMed Abstract»
Hu Y, Chen J, Wen J, et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus. BMC Pregnancy Childbirth. 2013;13:119.
PubMed Abstract»
Jourdain G, Ngo-Giang-Huong N, Harrison L, et al. Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med. 2018;378:911-23.
PubMed Abstract»
López M, Coll O. Chronic viral infections and invasive procedures: risk of vertical transmission and current recommendations. Fetal Diagn Ther. 2010;28:1-8.
PubMed Abstract»
Lee SD, Lo KJ, Tsai YT, et al. Role of caesarean section in prevention of mother-infant transmission of hepatitis B virus. Lancet. 1988;2:833-4.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Pan CQ, Zou HB, Chen Y, et al. Cesarean section reduces perinatal transmission of hepatitis B virus infection from hepatitis B surface antigen-positive women to their infants. Clin Gastroenterol Hepatol. 2013;11:1349-55.
PubMed Abstract»
Song YM, Sung J, Yang S, Choe YH, Chang YS, Park WS. Factors associated with immunoprophylaxis failure against vertical transmission of hepatitis B virus. Eur J Pediatr. 2007;166:813-8.
PubMed Abstract»
Towers CV, Asrat T, Rumney P. The presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood. Am J Obstet Gynecol. 2001;184:1514-8.
PubMed Abstract»
Tran TT. Hepatitis B in Pregnancy. Clin Infect Dis. 2016;62 Suppl 4:S314-7.
PubMed Abstract»
Wang DD, Yi LZ, Wu LN, et al. Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission. Biomed Environ Sci. 2019;32:315-323.
PubMed Abstract»
Xu DZ, Yan YP, Choi BC, et al. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol. 2002;67:20-6.
PubMed Abstract»
Xu DZ, Yan YP, Zou S, et al. Role of placental tissues in the intrauterine transmission of hepatitis B virus. Am J Obstet Gynecol. 2001;185:981-7.
PubMed Abstract»
Xu ZY, Liu CB, Francis DP, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial. Pediatrics. 1985;76:713-8.
PubMed Abstract»
Yi W, Pan CQ, Hao J, et al. Risk of vertical transmission of hepatitis B after amniocentesis in HBs antigen-positive mothers. J Hepatol. 2014;60:523-9.
PubMed Abstract»
Zhang SL, Yue YF, Bai GQ, Shi L, Jiang H. Mechanism of intrauterine infection of hepatitis B virus. World J Gastroenterol. 2004;10:437-8.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Management of Women with Chronic HBV in Pregnancy

Alexander JM, Ramus R, Jackson G, Sercely B, Wendel GD Jr. Risk of hepatitis B transmission after amniocentesis in chronic hepatitis B carriers. Infect Dis Obstet Gynecol. 1999;7:283-6.
PubMed Abstract»
Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63:319-33.
PubMed Abstract»
Chen HL, Lee CN, Chang CH, et al. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus. Hepatology. 2015;62:375-86.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21:70-84.
PubMed Abstract»
Han GR, Cao MK, Zhao W, et al. A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection. J Hepatol. 2011;55:1215-21.
PubMed Abstract»
Kazim SN, Wakil SM, Khan LA, Hasnain SE, Sarin SK. Vertical transmission of hepatitis B virus despite maternal lamivudine therapy. Lancet. 2002;359:1488-9.
PubMed Abstract»
Li XM, Shi MF, Yang YB, et al. Effect of hepatitis B immunoglobulin on interruption of HBV intrauterine infection. World J Gastroenterol. 2004;10:3215-7.
PubMed Abstract»
Li XM, Yang YB, Hou HY, et al. Interruption of HBV intrauterine transmission: a clinical study. World J Gastroenterol. 2003;9:1501-3.
PubMed Abstract»
Nguyen V, Tan PK, Greenup AJ, et al. Anti-viral therapy for prevention of perinatal HBV transmission: extending therapy beyond birth does not protect against post-partum flare. Aliment Pharmacol Ther. 2014;39:1225-34.
PubMed Abstract»
Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374:2324-34.
PubMed Abstract»
Samadi Kochaksaraei G, Castillo E, Sadler MD, et al. Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America. Aliment Pharmacol Ther. 2020;52:1707-16.
PubMed Abstract»
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Shi Z, Yang Y, Ma L, Li X, Schreiber A. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis. Obstet Gynecol. 2010;116:147-59.
PubMed Abstract»
Silverman NS. Hepatitis B Screening in Pregnant Women: A Perspective on the New USPSTF Recommendations. JAMA. 2019;322:312-4.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. J Viral Hepat. 2003;10:294-7.
PubMed Abstract»
Zeng QL, Yu ZJ, Ji F, et al. Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study. Clin Infect Dis. 2021;73:e3324-e3332.
PubMed Abstract»
Zeng QL, Zhang HX, Zhang JY, et al. Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study. Clin Gastroenterol Hepatol. 2021;S1542-3565(21)01306-9.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Management of Acute HBV in Pregnancy

Degertekin B, Lok AS. Indications for therapy in hepatitis B. Hepatology. 2009;49:S129-37.
PubMed Abstract»
Han YT, Sun C, Liu CX, et al. Clinical features and outcome of acute hepatitis B in pregnancy. BMC Infect Dis. 2014;14:368.
PubMed Abstract»
Jonas MM. Hepatitis B and pregnancy: an underestimated issue. Liver Int. 2009;29 Suppl 1:133-9.
PubMed Abstract»
Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374:2324-34.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Sookoian S. Liver disease during pregnancy: acute viral hepatitis. Ann Hepatol. 2006;5:231-6.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Safety of Antivirals During Pregnancy

Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry Interim Report for 1 January 1989 through 31 August 2022. Wilmington, NC: Registry Coordinating Center; 2022.
Antiretroviral Pregnancy Registry (APR)»
Chen HL, Lee CN, Chang CH, et al. Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus. Hepatology. 2015;62:375-86.
PubMed Abstract»
Ding Y, Cao L, Zhu L, et al. Efficacy and safety of tenofovir alafenamide fumarate for preventing mother-to-child transmission of hepatitis B virus: a national cohort study. Aliment Pharmacol Ther. 2020;52:1377-86.
PubMed Abstract»
European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group.. Nucleoside reverse transcriptase inhibitor backbones and pregnancy outcomes. AIDS. 2019;33:295-304.
PubMed Abstract»
Jacobson DL, Patel K, Williams PL, et al. Growth at 2 Years of Age in HIV-exposed Uninfected Children in the United States by Trimester of Maternal Antiretroviral Initiation. Pediatr Infect Dis J. 2017;36:189-197.
PubMed Abstract»
Jourdain G, Ngo-Giang-Huong N, Harrison L, et al. Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med. 2018;378:911-23.
PubMed Abstract»
Mofenson LM, Baggaley RC, Mameletzis I. Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding. AIDS. 2017 Jan 14;31:213-32.
PubMed Abstract»
Pan CQ, Duan Z, Dai E, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374:2324-34.
PubMed Abstract»
Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Recommendations for use of antiretroviral drugs during pregnancy: pregnant people with HIV who have never received antiretroviral drugs (antiretroviral naive). January 31, 2024.
HIV.gov»
Shi Z, Yang Y, Ma L, Li X, Schreiber A. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis. Obstet Gynecol. 2010;116:147-59.
PubMed Abstract»
Siberry GK, Jacobson DL, Kalkwarf HJ, et al. Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy. Clin Infect Dis. 2015;61:996-1003.
PubMed Abstract»
Sylvester-Armstrong KR, Duff P. Evidence for Use of Tenofovir in Pregnancy to Prevent Perinatal Transmission of Hepatitis B Infection. Clin Obstet Gynecol. 2019;62:835-845.
PubMed Abstract»
Wang L, Kourtis AP, Ellington S, Legardy-Williams J, Bulterys M. Safety of tenofovir during pregnancy for the mother and fetus: a systematic review. Clin Infect Dis. 2013;57:1773-81.
PubMed Abstract»
Zeng QL, Yu ZJ, Ji F, et al. Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study. Clin Infect Dis. 2021;73:e3324-e3332.
PubMed Abstract»
Zeng QL, Zhang HX, Zhang JY, et al. Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study. Clin Gastroenterol Hepatol. 2021;S1542-3565(21)01306-9.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Hepatitis B Flares During Pregnancy and in the Postpartum Period

Chang CY, Aziz N, Poongkunran M, et al. Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B. Am J Gastroenterol. 2016;111:1410-1415.
PubMed Abstract»
Chang CY, Aziz N, Poongkunran M, et al. Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B. J Clin Gastroenterol. 2018;52:255-261.
PubMed Abstract»
Giles M, Visvanathan K, Lewin S, et al. Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B. Gut. 2015;64:1810-5.
PubMed Abstract»
Nguyen V, Tan PK, Greenup AJ, et al. Anti-viral therapy for prevention of perinatal HBV transmission: extending therapy beyond birth does not protect against post-partum flare. Aliment Pharmacol Ther. 2014;39:1225-34.
PubMed Abstract»
Samadi Kochaksaraei G, Castillo E, Sadler MD, et al. Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America. Aliment Pharmacol Ther. 2020;52:1707-16.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Management of Neonates Born to HBsAg-Positive Mothers

Advisory Committee on Immunization Practices (ACIP). Recommended Child and Adolescent Immunization Schedule for ages 18 years or younger, United States, 2019.
ACIP»
Centers for Disease Control and Prevention (CDC). Postvaccination serologic testing results for infants aged ≤24 months exposed to hepatitis B virus at birth: United States, 2008-2011. MMWR Morb Mortal Wkly Rep. 2012;61:768-71.
PubMed Abstract»
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev. 2006;:CD004790.
PubMed Abstract»
Lo KJ, Lee SD, Tsai YT, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in infants born to HBeAg-positive HBsAg-carrier mothers. Hepatology. 1988;8:1647-50.
PubMed Abstract»
Lobstein S, Faber R, Tillmann HL. Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany. Digestion. 2011;83:76-82.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
McMahon BJ, Bruden DL, Petersen KM, et al. Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up. Ann Intern Med. 2005;142:333-41.
PubMed Abstract»
Reddick KL, Jhaveri R, Gandhi M, James AH, Swamy GK. Pregnancy outcomes associated with viral hepatitis. J Viral Hepat. 2011;18:e394-8.
PubMed Abstract»
Saari TN. Immunization of preterm and low birth weight infants. American Academy of Pediatrics Committee on Infectious Diseases. Pediatrics. 2003;112:193-8.
PubMed Abstract»
Safir A, Levy A, Sikuler E, Sheiner E. Maternal hepatitis B virus or hepatitis C virus carrier status as an independent risk factor for adverse perinatal outcome. Liver Int. 2010;30:765-70.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Tan J, Huang S, He G, et al. Maternal hepatitis B surface antigen carrier status and its impact on neonatal outcomes: a cohort study of 21 947 singleton newborns in China. J Matern Fetal Neonatal Med. 2017;30:2219-2224.
PubMed Abstract»
Tse KY, Ho LF, Lao T. The impact of maternal HBsAg carrier status on pregnancy outcomes: a case-control study. J Hepatol. 2005;43:771-5.
PubMed Abstract»
Wong S, Chan LY, Yu V, Ho L. Hepatitis B carrier and perinatal outcome in singleton pregnancy. Am J Perinatol. 1999;16:485-8.
PubMed Abstract»
Module 3 » Lesson 2. Preventing HBV Perinatal Transmission

Breastfeeding in HBsAg-Positive Mothers

Beasley RP, Stevens CE, Shiao IS, Meng HC. Evidence against breast-feeding as a mechanism for vertical transmission of hepatitis B. Lancet. 1975;2:740-1.
PubMed Abstract»
Benaboud S, Pruvost A, Coffie PA, et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d'Ivoire, in the ANRS 12109 TEmAA Study, Step 2. Antimicrob Agents Chemother. 2011;55:1315-7.
PubMed Abstract»
Corbett AH, Kayira D, White NR, et al. Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post-partum: results of the BAN Study. Antivir Ther. 2014;19:587-95.
PubMed Abstract»
Ehrhardt S, Xie C, Guo N, Nelson K, Thio CL. Breastfeeding while taking lamivudine or tenofovir disoproxil fumarate: a review of the evidence. Clin Infect Dis. 2015;60:275-8.
PubMed Abstract»
Ghaffar YA, elSobky MK, Raouf AA, Dorgham LS. Mother-to-child transmission of hepatitis B virus in a semirural population in Egypt. J Trop Med Hyg. 1989;92:20-6.
PubMed Abstract»
Hill JB, Sheffield JS, Kim MJ, Alexander JM, Sercely B, Wendel GD. Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B carriers. Obstet Gynecol. 2002;99:1049-52.
PubMed Abstract»
Mirochnick M, Taha T, Kreitchmann R, et al. Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their infants during the first week of life. J Acquir Immune Defic Syndr. 2014;65:33-41.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
André FE, Zuckerman AJ. Review: protective efficacy of hepatitis B vaccines in neonates. J Med Virol. 1994;44:144-51.
PubMed Abstract»
Beasley RP, Hwang LY, Lee GC, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;2:1099-102.
PubMed Abstract»
Brown RS Jr, McMahon BJ, Lok AS, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology. 2016;63:319-33.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). 2020 Viral Hepatitis Surveillance Report—Hepatitis B. Published September 2022.
CDC»
Chen HL, Lin LH, Hu FC, et al. Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV. Gastroenterology. 2012;142:773-781.e2.
PubMed Abstract»
Dionne-Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214:6-14.
PubMed Abstract»
European Association For The Study Of The Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98.
PubMed Abstract»
Funk AL, Lu Y, Yoshida K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: a systematic review and meta-analysis. Lancet Infect Dis. 2021;21:70-84.
PubMed Abstract»
Greenup AJ, Tan PK, Nguyen V, et al. Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus. J Hepatol. 2014;61:502-7.
PubMed Abstract»
Jourdain G, Ngo-Giang-Huong N, Cressey TR, et al. Prevention of mother-to-child transmission of hepatitis B virus: a phase III, placebo-controlled, double-blind, randomized clinical trial to assess the efficacy and safety of a short course of tenofovir disoproxil fumarate in women with hepatitis B virus e-antigen. BMC Infect Dis. 2016;16:393.
PubMed Abstract»
Ko SC, Fan L, Smith EA, Fenlon N, Koneru AK, Murphy TV. Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000-2009. J Pediatric Infect Dis Soc. 2016;5:114-21.
PubMed Abstract»
Koneru A, Fenlon N, Schillie S, Williams C, Weng MK, Nelson N. National Perinatal Hepatitis B Prevention Program: 2009-2017. Pediatrics. 2021;147:e20201823.
PubMed Abstract»
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev. 2006;:CD004790.
PubMed Abstract»
Li B, Liu Z, Liu X, et al. Efficacy and safety of tenofovir disoproxil fumarate and tenofovir alafenamide fumarate in preventing HBV vertical transmission of high maternal viral load. Hepatol Int. 2021;15:1103-8.
PubMed Abstract»
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005;54:1-31.
PubMed Abstract»
Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis. 2016;20:607-28.
PubMed Abstract»
Pan CQ, Han GR, Jiang HX, et al. Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B. Clin Gastroenterol Hepatol. 2012 May;10:520-6.
PubMed Abstract»
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Stevens CE, Taylor PE, Tong MJ, et al. Yeast-recombinant hepatitis B vaccine. Efficacy with hepatitis B immune globulin in prevention of perinatal hepatitis B virus transmission. JAMA. 1987;257:2612-6.
PubMed Abstract»
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
U.S. Preventive Services Task Force. Screening for hepatitis B virus infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2009;150:869-73, W154.
PubMed Abstract»
US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Hepatitis B Virus Infection in Pregnant Women: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2019;322:349-54.
PubMed Abstract»
Wen WH, Chang MH, Zhao LL, et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 2013;59:24-30.
PubMed Abstract»
Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71:477-83.
PubMed Abstract»
Xu WM, Cui YT, Wang L, et al. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat. 2008;16:94-103.
PubMed Abstract»
Xu ZY, Liu CB, Francis DP, et al. Prevention of perinatal acquisition of hepatitis B virus carriage using vaccine: preliminary report of a randomized, double-blind placebo-controlled and comparative trial. Pediatrics. 1985;76:713-8.
PubMed Abstract»
Zeng QL, Yu ZJ, Ji F, et al. Tenofovir Alafenamide to Prevent Perinatal Hepatitis B Transmission: A Multicenter, Prospective, Observational Study. Clin Infect Dis. 2021;73:e3324-e3332.
PubMed Abstract»

Lesson 3. Occupational HBV Postexposure Prophylaxis

Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Background

Beltrami EM, Williams IT, Shapiro CN, Chamberland ME. Risk and management of blood-borne infections in health care workers. Clin Microbiol Rev. 2000;13:385-407.
PubMed Abstract»
Boal WL, Leiss JK, Sousa S, Lyden JT, Li J, Jagger J. The national study to prevent blood exposure in paramedics: exposure reporting. Am J Ind Med. 2008;51:213-22.
PubMed Abstract»
Bond WW, Favero MS, Petersen NJ, Gravelle CR, Ebert JW, Maynard JE. Survival of hepatitis B virus after drying and storage for one week. Lancet. 1981;1:550-1.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). Workbook for Designing, Implementing, and Evaluating a Sharps Injury Prevention Program. 2008.
CDC»
Dement JM, Epling C, Ostbye T, Pompeii LA, Hunt DL. Blood and body fluid exposure risks among health care workers: results from the Duke Health and Safety Surveillance System. Am J Ind Med. 2004;46:637-48.
PubMed Abstract»
Denault D, Gardner H. OSHA Bloodborne Pathogen Standards. StatPearls Publishing; 2022 Jan.
PubMed Abstract»
Denes AE, Smith JL, Maynard JE, Doto IL, Berquist KR, Finkel AJ. Hepatitis B infection in physicians. Results of a nationwide seroepidemiologic survey. JAMA. 1978;239:210-12.
PubMed Abstract»
Dienstag JL, Ryan DM. Occupational exposure to hepatitis B virus in hospital personnel: infection or immunization? Am J Epidemiol. 1982;115:26-39.
PubMed Abstract»
Gerberding JL. Management of occupational exposures to blood-borne viruses. N Engl J Med. 1995;332:444-51.
PubMed Abstract»
Gershon RR, Pearson JM, Sherman MF, Samar SM, Canton AN, Stone PW. The prevalence and risk factors for percutaneous injuries in registered nurses in the home health care sector. Am J Infect Control. 2009;37:525-33.
PubMed Abstract»
Gershon RR, Qureshi KA, Pogorzelska M, et al. Non-hospital based registered nurses and the risk of bloodborne pathogen exposure. Ind Health. 2007;45:695-704.
PubMed Abstract»
International Healthcare Worker Safety Center, University of Virginia. U.S. EPINet Sharps Injury and Blood and Body Fluid Exposure Surveillance Research Group. Sharps Injury Data Report for 1997-2011.
EPINet»
Mahoney FJ, Stewart K, Hu H, Coleman P, Alter MJ. Progress toward the elimination of hepatitis B virus transmission among health care workers in the United States. Arch Intern Med. 1997;157:2601-5.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Segal HE, Llewellyn CH, Irwin G, Bancroft WH, Boe GP, Balaban DJ. Hepatitis B antigen and antibody in the U.S. Army: prevalence in health care personnel. Am J Public Health. 1976;66:667-71.
PubMed Abstract»
U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001;50:1-52.
PubMed Abstract»
Williams WW, Lu PJ, O'Halloran A, et al. Surveillance of Vaccination Coverage among Adult Populations - United States, 2015. MMWR Surveill Summ. 2017;66:1-28.
PubMed Abstract»
Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Risk of HBV with Occupational Exposures

Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001;50:1-52.
PubMed Abstract»
Werner BG, Grady GF. Accidental hepatitis-B-surface-antigen-positive inoculations. Use of e antigen to estimate infectivity. Ann Intern Med. 1982;97:367-9.
PubMed Abstract»
Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Initial Approach to Postexposure Prophylaxis

Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Interventions for HBV Occupational Postexposure Prophylaxis

Lu PJ, Hung MC, Srivastav A, et al. Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018. MMWR Surveill Summ. 2021;70:1-26.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001;50:1-52.
PubMed Abstract»
Williams WW, Lu PJ, O'Halloran A, et al. Surveillance of Vaccination Coverage among Adult Populations - United States, 2015. MMWR Surveill Summ. 2017;66:1-28.
PubMed Abstract»
Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Management of Occupational Exposure to HBV

Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Monitoring of HCP after Occupational HBV Exposure

Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Module 3 » Lesson 3. Occupational HBV Postexposure Prophylaxis

Efficacy of Occupational Postexposure Prophylaxis for HBV

Centers for Disease Control and Prevention (CDC). Postvaccination serologic testing results for infants aged ≤24 months exposed to hepatitis B virus at birth: United States, 2008-2011. MMWR Morb Mortal Wkly Rep. 2012;61:768-71.
PubMed Abstract»
Grady GF, Lee VA, Prince AM, et al. Hepatitis B immune globulin for accidental exposures among medical personnel: final report of a multicenter controlled trial. J Infect Dis. 1978;138:625-38.
PubMed Abstract»
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev. 2006;:CD004790.
PubMed Abstract»
Mitsui T, Iwano K, Suzuki S, et al. Combined hepatitis B immune globulin and vaccine for postexposure prophylaxis of accidental hepatitis B virus infection in hemodialysis staff members: comparison with immune globulin without vaccine in historical controls. Hepatology. 1989;10:324-7.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Seeff LB, Zimmerman HJ, Wright EC, et al. A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study. Gastroenterology. 1977;72:111-21.
PubMed Abstract»
Centers for Disease Control and Prevention (CDC). Postvaccination serologic testing results for infants aged ≤24 months exposed to hepatitis B virus at birth: United States, 2008-2011. MMWR Morb Mortal Wkly Rep. 2012;61:768-71.
PubMed Abstract»
Floreani A, Baldo V, Cristofoletti M, et al. Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers. Vaccine. 2004;22:607-10.
PubMed Abstract»
Gara N, Abdalla A, Rivera E, et al. Durability of antibody response against hepatitis B virus in healthcare workers vaccinated as adults. Clin Infect Dis. 2014;60:505-13.
PubMed Abstract»
Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis. 1999;179:489-92.
PubMed Abstract»
Kidd-Ljunggren K, Holmberg A, Bläckberg J, Lindqvist B. High levels of hepatitis B virus DNA in body fluids from chronic carriers. J Hosp Infect. 2006;64:352-7.
PubMed Abstract»
Kubba AK, Taylor P, Graneek B, Strobel S. Non-responders to hepatitis B vaccination: a review. Commun Dis Public Health. 2003;6:106-12.
PubMed Abstract»
Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Cochrane Database Syst Rev. 2006;:CD004790.
PubMed Abstract»
Louther J, Feldman J, Rivera P, Villa N, DeHovitz J, Sepkowitz KA. Hepatitis B vaccination program at a New York City hospital: seroprevalence, seroconversion, and declination. Am J Infect Control. 1998;26:423-7.
PubMed Abstract»
Lu PJ, Byrd KK, Murphy TV, Weinbaum C. Hepatitis B vaccination coverage among high-risk adults 18-49 years, U.S., 2009. Vaccine. 2011;29:7049-57.
PubMed Abstract»
Lu PJ, Hung MC, Srivastav A, et al. Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018. MMWR Surveill Summ. 2021;70:1-26.
PubMed Abstract»
Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep. 2006;55:1-33.
PubMed Abstract»
Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67:455-8.
PubMed Abstract»
Schillie S, Murphy TV, Sawyer M, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR Recomm Rep. 2013;62:1-19.
PubMed Abstract»
Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67:1-31.
PubMed Abstract»
Schillie S, Walker T, Veselsky S, et al. Outcomes of infants born to women infected with hepatitis B. Pediatrics. 2015;135:e1141-7.
PubMed Abstract»
Sepkowitz KA. Occupationally acquired infections in health care workers. Part II. Ann Intern Med. 1996;125:917-28.
PubMed Abstract»
Simard EP, Miller JT, George PA, et al. Hepatitis B vaccination coverage levels among healthcare workers in the United States, 2002-2003. Infect Control Hosp Epidemiol. 2007;28:783-90.
PubMed Abstract»
Sjogren MH. Prevention of hepatitis B in nonresponders to initial hepatitis B virus vaccination. Am J Med. 2005;118 Suppl 10A:34S-39S.
PubMed Abstract»
Van Der Meeren O, Peterson JT, Dionne M, et al. Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus. Hum Vaccin Immunother. 2016;12:2197-2203.
PubMed Abstract»
West DJ. The risk of hepatitis B infection among health professionals in the United States: a review. Am J Med Sci. 1984;287:26-33.
PubMed Abstract»

Module 4. Other Topics

Lesson 1. Screening for Hepatocellular Carcinoma

Module 4 » Lesson 1. Screening for Hepatocellular Carcinoma

Epidemiology of HBV-Associated Hepatocellular Carcinoma (HCC)

Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109:542-53.
PubMed Abstract»
Beasley RP, Hwang LY, Lin CC, Chien CS. Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet. 1981;2:1129-33.
PubMed Abstract»
de Martel C, Maucort-Boulch D, Plummer M, Franceschi S. World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma. Hepatology. 2015;62:1190-200.
PubMed Abstract»
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-76.
PubMed Abstract»
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264-1273.e1.
PubMed Abstract»
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118-27.
PubMed Abstract»
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301-1314.
PubMed Abstract»
Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2007;5:938-45, 945.e1-4.
PubMed Abstract»
Kuper H, Tzonou A, Kaklamani E, et al. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer. 2000;85:498-502.
PubMed Abstract»
Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11:97-107.
PubMed Abstract»
Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
PubMed Abstract»
Momin BR, Pinheiro PS, Carreira H, Li C, Weir HK. Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017;123 Suppl 24:5059-5078.
PubMed Abstract»
National Cancer Institute. Surveillance, Epidemiology, and End Result Program: Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer.
NCI»
Tanaka Y, Kurbanov F, Mano S, et al. Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology. 2006;130:703-14.
PubMed Abstract»
Tapper EB, Parikh ND. Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study. BMJ. 2018;362:k2817.
PubMed Abstract»
U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on 2021 submission data (1999-2019): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. Released in June 2022.
CDC and NCI»
Wong MC, Jiang JY, Goggins WB, et al. International incidence and mortality trends of liver cancer: a global profile. Sci Rep. 2017;7:45846.
PubMed Abstract»
World Health Organization. Cancer Fact Sheets, 2018. WHO’s International Agency for Research on Cancer.
WHO»
World Health Organization. Liver Fact Sheet: Globocan, 2020. WHO’s International Agency for Research on Cancer.
WHO»
Module 4 » Lesson 1. Screening for Hepatocellular Carcinoma

Factors that Impact HBV-Associated HCC

Ahn J, Lim JK, Lee HM, et al. Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study. Am J Gastroenterol. 2016;111:1297-304.
PubMed Abstract»
Alfaiate D, Clément S, Gomes D, Goossens N, Negro F. Chronic hepatitis D and hepatocellular carcinoma: A systematic review and meta-analysis of observational studies. J Hepatol. 2020;73:533-9.
PubMed Abstract»
Chang MH, You SL, Chen CJ, et al. Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer. Gastroenterology. 2016;151:472-480.e1.
PubMed Abstract»
Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
PubMed Abstract»
Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol. 2011;26:628-38.
PubMed Abstract»
Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111-21.
PubMed Abstract»
Donato F, Tagger A, Gelatti U, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155:323-31.
PubMed Abstract»
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-76.
PubMed Abstract»
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118-27.
PubMed Abstract»
Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35-50.
PubMed Abstract»
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301-1314.
PubMed Abstract»
Gouas D, Shi H, Hainaut P. The aflatoxin-induced TP53 mutation at codon 249 (R249S): biomarker of exposure, early detection and target for therapy. Cancer Lett. 2009;286:29-37.
PubMed Abstract»
Hosaka T, Suzuki F, Kobayashi M, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology. 2013;58:98-107.
PubMed Abstract»
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-1438.
PubMed Abstract»
Kuper H, Tzonou A, Kaklamani E, et al. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer. 2000;85:498-502.
PubMed Abstract»
Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
PubMed Abstract»
Mittal S, Kramer JR, Omino R, et al. Role of Age and Race in the Risk of Hepatocellular Carcinoma in Veterans With Hepatitis B Virus Infection. Clin Gastroenterol Hepatol. 2018;16:252-9.
PubMed Abstract»
Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
PubMed Abstract»
Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4:439-74.
PubMed Abstract»
Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62:956-67.
PubMed Abstract»
Papatheodoridis GV, Idilman R, Dalekos GN, et al. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B. Hepatology. 2017;66:1444-1453.
PubMed Abstract»
Papatheodoridis GV, Sypsa V, Dalekos GN, et al. Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B. J Hepatol. 2020;72:1088-96.
PubMed Abstract»
Park JW, Chen M, Colombo M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 2015;35:2155-66.
PubMed Abstract»
Petrick JL, Campbell PT, Koshiol J, et al. Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project. Br J Cancer. 2018;118:1005-12.
PubMed Abstract»
Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int. 2016;36:1239-51.
PubMed Abstract»
Rizzo GEM, Cabibbo G, Craxì A. Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses. 2022;14:986.
PubMed Abstract»
Russo FP, Zanetto A, Pinto E, et al. Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand? Int J Mol Sci. 2022;23:500.
PubMed Abstract»
Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology. 2011;54:463-71.
PubMed Abstract»
Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168-74.
PubMed Abstract»
You SL, Yang HI, Chen CJ. Seropositivity of hepatitis B e antigen and hepatocellular carcinoma. Ann Med. 2004;36:215-24.
PubMed Abstract»
Yu MW, Yeh SH, Chen PJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst. 2005;97:265-72.
PubMed Abstract»
Yuen MF, Seto WK, Chow DH, et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007;12:1295-303.
PubMed Abstract»
Module 4 » Lesson 1. Screening for Hepatocellular Carcinoma

Prognosis of Persons Diagnosed with HCC

Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109:542-53.
PubMed Abstract»
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118-27.
PubMed Abstract»
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301-1314.
PubMed Abstract»
Momin BR, Pinheiro PS, Carreira H, Li C, Weir HK. Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017;123 Suppl 24:5059-5078.
PubMed Abstract»
National Cancer Institute. Surveillance, Epidemiology, and End Result Program: Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer.
NCI»
Module 4 » Lesson 1. Screening for Hepatocellular Carcinoma

Benefit of HCC Screening in Persons with HBV

Beal EW, Owen M, McNamara M, McAlearney AS, Tsung A. Patient-, Provider-, and System-Level Barriers to Surveillance for Hepatocellular Carcinoma in High-Risk Patients in the USA: a Scoping Review. J Gastrointest Cancer. 2022 Jul 26. Online ahead of print.
PubMed Abstract»
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.
PubMed Abstract»
Daher S, Massarwa M, Benson AA, Khoury T. Current and Future Treatment of Hepatocellular Carcinoma: An Updated Comprehensive Review. J Clin Transl Hepatol. 2018;6:69-78.
PubMed Abstract»
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118-27.
PubMed Abstract»
Farvardin S, Patel J, Khambaty M, et al. Patient-reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis. Hepatology. 2017;65:875-884.
PubMed Abstract»
Fateen W, Ryder SD. Screening for hepatocellular carcinoma: patient selection and perspectives. J Hepatocell Carcinoma. 2017;4:71-9.
PubMed Abstract»
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301-1314.
PubMed Abstract»
Goldberg DS, Taddei TH, Serper M, et al. Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis. Hepatology. 2017;65:864-874.
PubMed Abstract»
Kansagara D, Papak J, Pasha AS, et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med. 2014;161:261-9.
PubMed Abstract»
Momin BR, Pinheiro PS, Carreira H, Li C, Weir HK. Liver cancer survival in the United States by race and stage (2001-2009): Findings from the CONCORD-2 study. Cancer. 2017;123 Suppl 24:5059-5078.
PubMed Abstract»
Singal AG, Mittal S, Yerokun OA, et al. Hepatocellular Carcinoma Screening Associated with Early Tumor Detection and Improved Survival Among Patients with Cirrhosis in the US. Am J Med. 2017;130:1099-1106.e1.
PubMed Abstract»
Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11:e1001624.
PubMed Abstract»
Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:417-22.
PubMed Abstract»
Module 4 » Lesson 1. Screening for Hepatocellular Carcinoma

HCC Surveillance Testing Methods

Barbara L, Benzi G, Gaiani S, et al. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology. 1992;16:132-7.
PubMed Abstract»
Bird TG, Dimitropoulou P, Turner RM, et al. Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection. PLoS One. 2016;11:e0156801.
PubMed Abstract»
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-76.
PubMed Abstract»
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264-1273.e1.
PubMed Abstract»
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.
EASL»
Fetzer DT, Rodgers SK, Harris AC, et al. Screening and Surveillance of Hepatocellular Carcinoma: An Introduction to Ultrasound Liver Imaging Reporting and Data System. Radiol Clin North Am. 2017;55:1197-1209.
PubMed Abstract»
Gupta S, Bent S, Kohlwes J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med. 2003;139:46-50.
PubMed Abstract»
Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358-80.
PubMed Abstract»
Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2007;5:938-45, 945.e1-4.
PubMed Abstract»
Johnson PJ, Pirrie SJ, Cox TF, et al. The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers. Cancer Epidemiol Biomarkers Prev. 2014;23:144-53.
PubMed Abstract»
Lok AS, Sterling RK, Everhart JE, et al. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology. 2010;138:493-502.
PubMed Abstract»
Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
PubMed Abstract»
Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61:191-9.
PubMed Abstract»
Papatheodoridis G, Dalekos G, Sypsa V, et al. PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol. 2016;64:800-6.
PubMed Abstract»
Parikh A, Taouli B. Imaging of hepatocellular carcinoma: current concepts. Recent Results Cancer Res. 2013;190:33-55.
PubMed Abstract»
Rizzo GEM, Cabibbo G, Craxì A. Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses. 2022;14:986.
PubMed Abstract»
Santi V, Trevisani F, Gramenzi A, et al. Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol. 2010;53:291-7.
PubMed Abstract»
Sherman M, Peltekian KM, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology. 1995;22:432-8.
PubMed Abstract»
Simmons O, Fetzer DT, Yokoo T, et al. Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Aliment Pharmacol Ther. 2017;45:169-177.
PubMed Abstract»
Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30:37-47.
PubMed Abstract»
Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11:e1001624.
PubMed Abstract»
Su YH, Kim AK, Jain S. Liquid biopsies for hepatocellular carcinoma. Transl Res. 2018;201:84-97.
PubMed Abstract»
Talwalkar JA, Gores GJ. Diagnosis and staging of hepatocellular carcinoma. Gastroenterology. 2004;127:S126-32.
PubMed Abstract»
Tayob N, Lok AS, Do KA, Feng Z. Improved Detection of Hepatocellular Carcinoma by Using a Longitudinal Alpha-Fetoprotein Screening Algorithm. Clin Gastroenterol Hepatol. 2016;14:469-475.e2.
PubMed Abstract»
Tong MJ, Blatt LM, Kao VW. Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol. 2001;16:553-9.
PubMed Abstract»
Trinchet JC, Chaffaut C, Bourcier V, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology. 2011;54:1987-97.
PubMed Abstract»
United States Cancer Statistics (USCS). Liver and Intrahepatic bile duct cancer, United States—2006-2015. U.S. Cancer Statistics Data Briefs, No. 5. November 2018
CDC/NCI»
White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012. Gastroenterology. 2017;152:812-20.e5.
PubMed Abstract»
Yang JD, Addissie BD, Mara KC, et al. GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. Cancer Epidemiol Biomarkers Prev. 2019;28:531-8.
PubMed Abstract»
Yang JD, Mohamed EA, Aziz AO, et al. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium. Lancet Gastroenterol Hepatol. 2017;2:103-11.
PubMed Abstract»
Yuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50:80-8.
PubMed Abstract»
Module 4 » Lesson 1. Screening for Hepatocellular Carcinoma

AASLD Guidance for HCC Surveillance

Bruix J, Reig M, Sherman M. Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology. 2016;150:835-53.
PubMed Abstract»
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.
PubMed Abstract»
Díaz-González Á, Forner A. Surveillance for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol. 2016;30:1001-10.
PubMed Abstract»
Dalton-Fitzgerald E, Tiro J, Kandunoori P, Halm EA, Yopp A, Singal AG. Practice patterns and attitudes of primary care providers and barriers to surveillance of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13:791-8.e1.
PubMed Abstract»
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.
EASL»
Farvardin S, Patel J, Khambaty M, et al. Patient-reported barriers are associated with lower hepatocellular carcinoma surveillance rates in patients with cirrhosis. Hepatology. 2017;65:875-884.
PubMed Abstract»
Goldberg DS, Taddei TH, Serper M, et al. Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis. Hepatology. 2017;65:864-874.
PubMed Abstract»
Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358-80.
PubMed Abstract»
Kansagara D, Papak J, Pasha AS, et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med. 2014;161:261-9.
PubMed Abstract»
Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
PubMed Abstract»
Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
PubMed Abstract»
Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4:439-74.
PubMed Abstract»
Papatheodoridis G, Dalekos G, Sypsa V, et al. PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol. 2016;64:800-6.
PubMed Abstract»
Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62:956-67.
PubMed Abstract»
Papatheodoridis GV, Dalekos GN, Yurdaydin C, et al. Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir. J Hepatol. 2015;62:363-70.
PubMed Abstract»
Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med. 1996;101:422-34.
PubMed Abstract»
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
PubMed Abstract»
Sharma S, Khalili K, Nguyen GC. Non-invasive diagnosis of advanced fibrosis and cirrhosis. World J Gastroenterol. 2014;20:16820-30.
PubMed Abstract»
Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922-65.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Yang HI, Yuen MF, Chan HL, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12:568-74.
PubMed Abstract»
Yang JD, Addissie BD, Mara KC, et al. GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. Cancer Epidemiol Biomarkers Prev. 2019;28:531-8.
PubMed Abstract»

Additional References

Ahn J, Lim JK, Lee HM, et al. Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study. Am J Gastroenterol. 2016;111:1297-304.
PubMed Abstract»
Akinyemiju T, Abera S, Ahmed M, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol. 2017;3:1683-1691.
PubMed Abstract»
Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009;27:1485-91.
PubMed Abstract»
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-2.
PubMed Abstract»
Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
PubMed Abstract»
Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol. 2011;26:628-38.
PubMed Abstract»
Díaz-González Á, Reig M, Bruix J. Treatment of Hepatocellular Carcinoma. Dig Dis. 2016;34:597-602.
PubMed Abstract»
Donato F, Tagger A, Gelatti U, et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol. 2002;155:323-31.
PubMed Abstract»
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132:2557-76.
PubMed Abstract»
Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301-1314.
PubMed Abstract»
Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358-80.
PubMed Abstract»
Hosaka T, Suzuki F, Kobayashi M, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology. 2013;58:98-107.
PubMed Abstract»
Kim WR, Loomba R, Berg T, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B. Cancer. 2015;121:3631-8.
PubMed Abstract»
Konstantinou D, Deutsch M. The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viralinteractions and management. Ann Gastroenterol. 2015;28:221-8.
PubMed Abstract»
Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521-31.
PubMed Abstract»
Lim YS, Han S, Heo NY, Shim JH, Lee HC, Suh DJ. Mortality, liver transplantation, and hepatocellular carcinoma among patients with chronic hepatitis B treated with entecavir vs lamivudine. Gastroenterology. 2014;147:152-61.
PubMed Abstract»
Lin OS, Keeffe EB, Sanders GD, Owens DK. Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Aliment Pharmacol Ther. 2004;19:1159-72.
PubMed Abstract»
Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013;158:329-37.
PubMed Abstract»
Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
PubMed Abstract»
Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62:956-67.
PubMed Abstract»
Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int. 2016;36:1239-51.
PubMed Abstract»
Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1-98.
PubMed Abstract»
Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922-65.
PubMed Abstract»
Song P, Cai Y, Tang H, Li C, Huang J. The clinical management of hepatocellular carcinoma worldwide: A concise review and comparison of current guidelines from 2001 to 2017. Biosci Trends. 2017;11:389-98.
PubMed Abstract»
Tang AS, Thornton K, and HBV Primary Care Workgroup. Hepatitis B Management: Guidance for the Primary Care Provider. February 25, 2020.
HBV Primary Care Workgroup»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Tzartzeva K, Obi J, Rich NE, et al. Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology. 2018;154:1706-18.e1.
PubMed Abstract»
Yamashita S, Vauthey JN, Kaseb AO, et al. Prognosis of Fibrolamellar Carcinoma Compared to Non-cirrhotic Conventional Hepatocellular Carcinoma. J Gastrointest Surg. 2016;20:1725-31.
PubMed Abstract»

Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Background and Definitions

Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156-65.
PubMed Abstract»
Myint A, Tong MJ, Beaven SW. Reactivation of Hepatitis B Virus: A Review of Clinical Guidelines. Clin Liver Dis (Hoboken). 2020;15:162-7.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Pathophysiology of HBV Reactivation

Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118-29.
PubMed Abstract»
Martinez MG, Boyd A, Combe E, Testoni B, Zoulim F. Covalently closed circular DNA: The ultimate therapeutic target for curing HBV infections. J Hepatol. 2021;75:706-17.
PubMed Abstract»
Myint A, Tong MJ, Beaven SW. Reactivation of Hepatitis B Virus: A Review of Clinical Guidelines. Clin Liver Dis (Hoboken). 2020;15:162-7.
PubMed Abstract»
Wei L, Ploss A. Hepatitis B virus cccDNA is formed through distinct repair processes of each strand. Nat Commun. 2021;12:1591.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Clinical Features of HBV Reactivation

Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156-65.
PubMed Abstract»
Loomba R, Liang TJ. Hepatitis B Reactivation Associated With Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions. Gastroenterology. 2017;152:1297-1309.
PubMed Abstract»
Myint A, Tong MJ, Beaven SW. Reactivation of Hepatitis B Virus: A Review of Clinical Guidelines. Clin Liver Dis (Hoboken). 2020;15:162-7.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Risk Factors for HBV Reactivation

Bersoff-Matcha SJ, Cao K, Jason M, et al. Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System. Ann Intern Med. 2017;166:792-8.
PubMed Abstract»
Esteve M, Saro C, González-Huix F, Suarez F, Forné M, Viver JM. Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut. 2004;53:1363-5.
PubMed Abstract»
Hammond SP, Borchelt AM, Ukomadu C, Ho VT, Baden LR, Marty FM. Hepatitis B virus reactivation following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:1049-59.
PubMed Abstract»
Khiangte B, Kothakota SR, Sasidharan M, et al. Hepatitis B Reactivation in Liver Transplant Recipients With Hepatitis B Virus Core Antibody Positive Grafts: a Retrospective Study. J Clin Exp Hepatol. 2020;10:548-54.
PubMed Abstract»
Kim PS, Ho GY, Prete PE, Furst DE. Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepatitis B. Arthritis Care Res (Hoboken). 2012;64:1265-8.
PubMed Abstract»
Lee YH, Bae SC, Song GG. Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol. 2013;31:118-21.
PubMed Abstract»
Lee YH, Bae SC, Song GG. Hepatitis B virus reactivation in HBsAg-positive patients with rheumatic diseases undergoing anti-tumor necrosis factor therapy or DMARDs. Int J Rheum Dis. 2013;16:527-31.
PubMed Abstract»
Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148:519-28.
PubMed Abstract»
Mei T, Noguchi H, Hisadome Y, et al. Hepatitis B virus reactivation in kidney transplant patients with resolved hepatitis B virus infection: Risk factors and the safety and efficacy of preemptive therapy. Transpl Infect Dis. 2020;22:e13234.
PubMed Abstract»
Navarro R, Vilarrasa E, Herranz P, et al. Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective, multicentre study in a clinical setting. Br J Dermatol. 2013;168:609-16.
PubMed Abstract»
Ou P, Fang Z, Chen J. Hepatitis B reactivation in a chronic hepatitis C patient treated with ledipasvir and sofosbuvir: A case report. Clin Res Hepatol Gastroenterol. 2017;41:e17-e18.
PubMed Abstract»
Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011;90:359-71.
PubMed Abstract»
Paul S, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB. Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy: A Systematic Review and Meta-analysis. Ann Intern Med. 2016;164:30-40.
PubMed Abstract»
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-244.e3.
PubMed Abstract»
Perrillo RP, Martin P, Lok AS. Preventing hepatitis B reactivation due to immunosuppressive drug treatments. JAMA. 2015;313:1617-8.
PubMed Abstract»
Ryu HH, Lee EY, Shin K, et al. Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFα agents: a retrospective analysis of 49 cases. Clin Rheumatol. 2012;31:931-6.
PubMed Abstract»
Tsutsumi Y, Yamamoto Y, Ito S, et al. Hepatitis B virus reactivation with a rituximab-containing regimen. World J Hepatol. 2015;7:2344-51.
PubMed Abstract»
Wang C, Ji D, Chen J, et al. Hepatitis due to Reactivation of Hepatitis B Virus in Endemic Areas Among Patients With Hepatitis C Treated With Direct-acting Antiviral Agents. Clin Gastroenterol Hepatol. 2017;15:132-6.
PubMed Abstract»
Wei L, Chen D, Zhang B, et al. Long-term outcome and recurrence of hepatitis B virus following liver transplantation from hepatitis B surface antigen-positive donors in a Chinese population. J Viral Hepat. 2018;25:1576-81.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Assessing Risk for HBV Reactivation

Hsu C, Tsou HH, Lin SJ, et al. Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: a prospective study. Hepatology. 2014;59:2092-100.
PubMed Abstract»
Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31:2765-72.
PubMed Abstract»
Lau GK, Leung YH, Fong DY, et al. High hepatitis B virus (HBV) DNA viral load as the most important risk factor for HBV reactivation in patients positive for HBV surface antigen undergoing autologous hematopoietic cell transplantation. Blood. 2002;99:2324-30.
PubMed Abstract»
Lau GK, Yiu HH, Fong DY, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology. 2003;125:1742-9.
PubMed Abstract»
Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011;90:359-71.
PubMed Abstract»
Pei SN, Ma MC, Wang MC, et al. Analysis of hepatitis B surface antibody titers in B cell lymphoma patients after rituximab therapy. Ann Hematol. 2012;91:1007-12.
PubMed Abstract»
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-244.e3.
PubMed Abstract»
Seto WK, Chan TS, Hwang YY, et al. Hepatitis B reactivation in occult viral carriers undergoing hematopoietic stem cell transplantation: A prospective study. Hepatology. 2017;65:1451-61.
PubMed Abstract»
Seto WK, Chan TS, Hwang YY, et al. Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol. 2014;32:3736-43.
PubMed Abstract»
Shouval D, Shibolet O. Immunosuppression and HBV reactivation. Semin Liver Dis. 2013;33:167-77.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Yeo W, Zee B, Zhong S, et al. Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Br J Cancer. 2004;90:1306-11.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Risk Categories for HBV Reactivation

Di Bisceglie AM, Lok AS, Martin P, Terrault N, Perrillo RP, Hoofnagle JH. Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg? Hepatology. 2015;61:703-11.
PubMed Abstract»
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-244.e3.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

HBV Screening Prior to Initiation of Immunosuppression

Di Bisceglie AM, Lok AS, Martin P, Terrault N, Perrillo RP, Hoofnagle JH. Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg? Hepatology. 2015;61:703-11.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Data on Antiviral Therapy to Prevent HBV Reactivation

Chen XQ, Peng JW, Lin GN, Li M, Xia ZJ. The effect of prophylactic lamivudine on hepatitis B virus reactivation in HBsAg-positive patients with diffuse large B-cell lymphoma undergoing prolonged rituximab therapy. Med Oncol. 2012;29:1237-41.
PubMed Abstract»
Fung J, Lai CL, Seto WK, Yuen MF. Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B. J Antimicrob Chemother. 2011;66:2715-25.
PubMed Abstract»
Hsiao LT, Chiou TJ, Liu JH, et al. Extended lamivudine therapy against hepatitis B virus infection in hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2006;12:84-94.
PubMed Abstract»
Hsu C, Hsiung CA, Su IJ, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology. 2008;47:844-53.
PubMed Abstract»
Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312:2521-30.
PubMed Abstract»
Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31:2765-72.
PubMed Abstract»
Jang JW, Choi JY, Bae SH, et al. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology. 2006;43:233-40.
PubMed Abstract»
Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat. 2008;15:89-102.
PubMed Abstract»
Koukoulioti E, Brodzinski A, Mihm U, et al. Risk factors for resistance development against lamivudine during long-term treatment of chronic hepatitis B virus infections. Eur J Gastroenterol Hepatol. 2019;31:845-52.
PubMed Abstract»
Lau GK, Yiu HH, Fong DY, et al. Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology. 2003;125:1742-9.
PubMed Abstract»
Lok AS, Lai CL, Leung N, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125:1714-22.
PubMed Abstract»
Long M, Jia W, Li S, et al. A single-center, prospective and randomized controlled study: Can the prophylactic use of lamivudine prevent hepatitis B virus reactivation in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy? Breast Cancer Res Treat. 2011;127:705-12.
PubMed Abstract»
Loomba R, Rowley A, Wesley R, et al. Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy. Ann Intern Med. 2008;148:519-28.
PubMed Abstract»
Paul S, Saxena A, Terrin N, Viveiros K, Balk EM, Wong JB. Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy: A Systematic Review and Meta-analysis. Ann Intern Med. 2016;164:30-40.
PubMed Abstract»
Tang W, Chen L, Zheng R, et al. Prophylactic Effect of Lamivudine for Chemotherapy-Induced Hepatitis B Reactivation in Breast Cancer: A Meta-Analysis. PLoS One. 2015;10:e0128673.
PubMed Abstract»
Xu Z, Dai W, Wu YT, et al. Prophylactic effect of lamivudine on chemotherapy-induced hepatitis B virus reactivation in patients with solid tumour: A meta-analysis. Eur J Cancer Care (Engl). 2018;27:e12799.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Professional Society Recommendations for HBV Prophylactic Antiviral Therapy

Cerva C, Colagrossi L, Maffongelli G, et al. Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor. Clin Microbiol Infect. 2016;22:946.e1-946.e8.
PubMed Abstract»
Di Bisceglie AM, Lok AS, Martin P, Terrault N, Perrillo RP, Hoofnagle JH. Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg? Hepatology. 2015;61:703-11.
PubMed Abstract»
Huang H, Li X, Zhu J, et al. Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial. JAMA. 2014;312:2521-30.
PubMed Abstract»
Huang YH, Hsiao LT, Hong YC, et al. Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B. J Clin Oncol. 2013;31:2765-72.
PubMed Abstract»
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update. J Clin Oncol. 2020;38:3698-3715.
PubMed Abstract»
Liu WP, Wang XP, Zheng W, et al. Hepatitis B virus reactivation after withdrawal of prophylactic antiviral therapy in patients with diffuse large B cell lymphoma. Leuk Lymphoma. 2016;57:1355-62.
PubMed Abstract»
Nakaya A, Fujita S, Satake A, et al. Delayed HBV reactivation in rituximab-containing chemotherapy: How long should we continue anti-virus prophylaxis or monitoring HBV-DNA? Leuk Res. 2016;50:46-9.
PubMed Abstract»
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-244.e3.
PubMed Abstract»
Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT. American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:215-9.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Yang C, Qin B, Yuan Z, Chen L, Zhou HY.  Meta-analysis of prophylactic entecavir or lamivudine against hepatitis B virus reactivation. Ann Hepatol. 2016;15:501-11.
PubMed Abstract»
Yu S, Luo H, Pan M, et al. Comparison of entecavir and lamivudine in preventing HBV reactivation in lymphoma patients undergoing chemotherapy: a meta-analysis. Int J Clin Pharm. 2016;38:1035-43.
PubMed Abstract»
Zhang MY, Zhu GQ, Shi KQ, et al. Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation. Oncotarget. 2016;7:30642-58.
PubMed Abstract»
Module 4 » Lesson 2. Hepatitis B Reactivation in the Setting of Immunosuppression

Special Populations to Consider for HBV Reactivation

Altfeld M, Rockstroh JK, Addo M, et al. Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. J Hepatol. 1998;29:306-9.
PubMed Abstract»
Belperio PS, Shahoumian TA, Mole LA, Backus LI. Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral hepatitis C antivirals. Hepatology. 2017;66:27-36.
PubMed Abstract»
Bersoff-Matcha SJ, Cao K, Jason M, et al. Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System. Ann Intern Med. 2017;166:792-8.
PubMed Abstract»
Biggar RJ, Goedert JJ, Hoofnagle J. Accelerated loss of antibody to hepatitis B surface antigen among immunodeficient homosexual men infected with HIV. N Engl J Med. 1987;316:630-1.
PubMed Abstract»
Chen G, Wang C, Chen J, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis. Hepatology. 2017;66:13-26.
PubMed Abstract»
Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156-65.
PubMed Abstract»
Lazizi Y, Grangeot-Keros L, Delfraissy JF, et al. Reappearance of hepatitis B virus in immune patients infected with the human immunodeficiency virus type 1. J Infect Dis. 1988;158:666-7.
PubMed Abstract»
Liu CJ, Chuang WL, Sheen IS, et al. Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV. Gastroenterology. 2018;154:989-97.
PubMed Abstract»
Suda T, Shimakami T, Shirasaki T, et al. Reactivation of hepatitis B virus from an isolated anti-HBc positive patient after eradication of hepatitis C virus with direct-acting antiviral agents. J Hepatol. 2017;67:1108-11.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology. 2009;49:S138-45.
PubMed Abstract»
Vento S, Di Perri G, Garofano T, Concia E, Bassetti D. Reactivation of hepatitis B in AIDS. Lancet. 1989;2:108-9.
PubMed Abstract»
Wang C, Ji D, Chen J, et al. Hepatitis due to Reactivation of Hepatitis B Virus in Endemic Areas Among Patients With Hepatitis C Treated With Direct-acting Antiviral Agents. Clin Gastroenterol Hepatol. 2017;15:132-6.
PubMed Abstract»
Zhou K, Terrault N. Management of hepatitis B in special populations. Best Pract Res Clin Gastroenterol. 2017;31:311-20.
PubMed Abstract»
American Gastroenterological Association. AGA Institute Guidelines on Hepatitis B Reactivation (HBVr): Clinical Decision Support Tool. Gastroenterology. 2015;148:220.
AGA»
Chen G, Wang C, Chen J, et al. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis. Hepatology. 2017;66:13-26.
PubMed Abstract»
Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350:1118-29.
PubMed Abstract»
Katz LH, Fraser A, Gafter-Gvili A, Leibovici L, Tur-Kaspa R. Lamivudine prevents reactivation of hepatitis B and reduces mortality in immunosuppressed patients: systematic review and meta-analysis. J Viral Hepat. 2008;15:89-102.
PubMed Abstract»
Perrillo RP, Gish R, Falck-Ytter YT. American Gastroenterological Association Institute technical review on prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015;148:221-244.e3.
PubMed Abstract»
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-99.
PubMed Abstract»
Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57:1-20.
PubMed Abstract»

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