Challenges and Controversies

I would be inclined to switch to TAF because he is relatively young and will require antiviral therapy lifelong as a result of the cirrhosis. Although his creatinine is normal, he does have DM2 and is at risk of developing renal complications. Normally, I'd have this discussion with the patient and make a joint decision. The other significant variable is insurance coverage, with some insurance companies mandating that you show "failure" of either TDF or entecavir or a proven side effect from those regimens.

Tenofovir DF (TDF) is known to cause a reduction in estimated glomerular filtration rate (eGFR) in patients receiving TDF, in both those with HIV as well as those with chronic hepatitis B. This might manifest as simply a change in serum creatinine in the absence of anything else or at the other extreme, Fanconi syndrome (renal tubular injury with hypophosphatemia, metabolic acidosis). The exact population-based incidence of TDF nephrotoxicity is not well established, particularly among patients with chronic hepatitis B, but longterm safety data from the registration phase 3 trials suggest this is rare. Risk factors for this include baseline renal insufficiency (esp. eGFR<60), older age, low BMI, concurrent nephrotoxic agents and underlying comorbidities such as diabetes. Tenofovir alafenamide (TAF) is a newer formulation of the drug that is associated with much lower plasma drug levels and lower risk of nephrotoxicity. But TDF is now generic while TAF is not.

For this patient, I would consider a switch to TAF but want more information. I would evaluate if there was indeed a change in eGFR, as that would sway me more to favor TAF - a serum creatinine of 0.9 may be “normal” but if his baseline Cr were 0.5 before TDF was started, that would be noteworthy. If he has evidence of hypertension, albuminuria or is already on a ACE-inhibitor, that would sway me as well since that is an indication that he has or is at risk of kidney disease. If he were older (60 years or more), I would likely change to TAF regardless since we lose eGFR for each advancing age. This patient has compensated cirrhosis, so that means he’s going to need to be on therapy for a very long time so this must be factored into the decision-making as well. It is reasonable if his diabetes is well-controlled (without the other clinical features) to continue TDF with regular renal monitoring (urinalysis and renal panels) every 6 months.