Challenges and Controversies

The risk of hepatitis B flare—defined as an ALT elevation greater than 5 times the upper limit of normal (ULN)—is approximately 20% within the first year after discontinuing oral antiviral therapy. The risk of more severe flares, with ALT levels exceeding 10 times the ULN, is around 10%. However, patients who are inactive carriers of hepatitis B virus (as suggested here) have a significantly lower likelihood of reactivation or flare following therapy withdrawal compared to those with active disease. Nevertheless, hepatitis C treatment and clearance can alter the immunologic control of HBV, potentially shifting patients from a low-replication phase to active replication, thereby increasing the risk of HBV reactivation. For this particular patient, I would recommend a shared decision-making approach regarding the continuation or cessation of HBV therapy. It is essential that she understands the importance of close lab monitoring after withdrawal and the need for prompt retreatment if HBV DNA levels rise above 4–5 log₁₀ IU/mL or if there is a significant elevation in ALT. Note: I would likely encourage continuation of TDF if the patient has cirrhosis, as the risk of HBV reactivation is much greater in that context.

I would discuss the situation with the patient and make a joint decision. I am also assuming that she does not have significant fibrosis since if she did, then I would continue TDF indefinitely. Without significant fibrosis, any of the other scenarios listed are viable options. She was started on HBV treatment at the time of initiation of HCV DAA treatment as recommended by guidelines since her HBV DNA was detectable and is at increased risk for a flare. These flares occur with HCV treatment since HCV increases the interferon stimulated gene (ISG) response, which can suppress HBV replication. Once the HCV is treated, the ISG response decreases allowing HBV to replicate. In this patient, we don't know how much of a role that ISG response had in controlling her HBV. So, there is a risk of reactivation of HBV when stopping TDF but it is not clear what the risk is in her. If the joint decision is to stop, then HBV DNA and ALT/AST should be closely monitored.