Hepatitis B Reactivation in the DAA Era: Minding the Gap Between the Black Box and Clinical Practice

The US Food and Drug Administration recently issued a black box warning regarding the risk of hepatitis B virus (HBV) reactivation with direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-coinfected individuals. The warning included all HBV infection, active and resolved, which, along with the lack of consensus among the gastroenterology and hepatology guidelines, have left clinicians unsure on how to proceed. Recent data have filled some knowledge gaps regarding the true risk of HBV reactivation in HCV treatment. The clinical data pertaining to the risk of reactivation in active and resolved HBV infection are reviewed, and potential prevention and management strategies are proposed, noting there are still some knowledge gaps remaining.

Recent large prospective studies of HBV/HCV-coinfected patients, along with the largest meta-analysis of such patients to date, provide additional insight into the risk of HBV reactivation with HCV antiviral treatment. Subclinical HBV reactivation is not uncommon, occurring in about 25% of patients, but the risk of clinically significant events such as hepatitis remains low in HBsAg-positive individuals, and even lower in isolated HBcAb-positive patients. However, recent case reports have brought to light particular situations, such as concomitant immunosuppression, as potential pitfalls to the previous low risk of reactivation attributed to resolved infection.

Recent prospective data and a large meta-analysis confirm that clinically significant HBV reactivation remains an uncommon event with the use of DAAs in HBsAg-positive patients, and even rarer in isolated HBcAb-positive cases.