Challenges and Controversies

This patient has HBV/HCV coinfection. Patients with HCV infection who are HbsAg positive consistent with chronic HBV infection are the group of patients at highest risk for HBV reactivation during HCV treatment with one systematic review reporting HBV reactivation in up to 24% of patients with chronic hepatitis B undergoing HCV treatment with oral direct acting antivirals (Mucke et al Lancet Gastroenterol Hepatol. 2018). Although not all cases of HBV reactivation are clinically evident, HBV reactivation can lead to fulminant liver disease with reports of liver failure requiring liver transplantation or resulting in death. As such, the risk of HBV reactivation should be considered and, if found, acted upon. HBV reactivation is less likely at lower pre-treatment HBV DNA levels. In this case, I would go ahead and start HCV treatment immediately and start prophylactic HBV therapy simultaneously. Because he does not have HIV infection, I would treat HBV with entecavir which is well tolerated without significant side effects in most patients. I would do this because 1) The benefit of immediate HCV treatment and cure without loss to follow up is high. 2) With him on prophylactic therapy the risk of HBV reactivation is significantly lower. While an alternative approach might be to check liver enzymes and HBV DNA every 4 weeks while on therapy and for up to 12 weeks after, requiring the patient to go for repeated blood draws and the cost of laboratory testing seems excessively burdensome compared to initiation of entecavir around the same time as HCV treatment initiation and continuation for up to 12 weeks after end of treatment. This approach also provides an opportunity to engage the patient in ongoing follow up for HBV care.

This individual has chronic hepatitis B with a low HBV viral load and normal ALT levels, consistent with a low replication state (previously referred to as an "inactive carrier"). In this context, antiviral therapy for HBV is not typically indicated. However, he also requires treatment for hepatitis C. Direct-acting antiviral (DAA) therapy for HCV has been associated with HBV reactivation in individuals co-infected with both viruses. HBV reactivation can lead to severe, potentially life-threatening hepatitis flares.

To mitigate this risk, current AASLD/IDSA guidelines recommend initiating HBV-active antiviral therapy preemptively in those with chronic HBV. They give the option of close monitoring without therapy in those with low or undetectable HBV, but I would favor treating since we do not have sufficient data to say that patients like ours with low but quantifiable virus are similarly at low risk of HBV reactivation with DAA compared with those who are undetectable.

While the guidelines do not specify the exact timing relative to DAA initiation, starting HBV treatment concurrently with HCV therapy is a reasonable approach—especially given the patient’s low baseline HBV DNA level, which should allow for rapid viral suppression. Although it is an option to stagger the therapies by a week or more to monitor for drug tolerability, HBV antivirals are generally well tolerated and effective. Therefore, delaying HBV treatment is not necessary in this case. Staggering might be more appropriate if the HBV viral load were higher, but waiting for full suppression before starting HCV therapy could lead to unnecessary delays and increase the risk of loss to follow-up.