Challenges and Controversies

This patient with chronic hepatitis C has a serological profile consistent with isolated anti-HBc. Available data suggest a very low risk of hepatitis B reactivation in patients with isolated anti-HBc (0.1-1%). These infrequent cases of reactivation have also not been associated with clinically significant hepatitis. As such, I would treat for hepatitis C with no on-treatment monitoring. In this clinical scenario, without significant transaminase elevation to suggest the patient is in the window period of acute HBV infection, the isolated anti-HBc most likely represents resolved HBV with loss of anti-HBs. For this patient, I would consider HBV vaccination.

Isolated anti-HBV core antibody positivity (IAHBC) is more common in patients with HCV-positive RNA levels than in those with negative HCV RNA levels and is not an uncommon finding when preparing to initiate HCV treatment. IAHBC can be seen in patients with: 1) HBV infection with initial seroconversion to HBV surface Ab positivity and waning immunity, with loss of HBV surface Ab (most common); 2) low-level chronic infection (occult HBV viremia); 3) resolving acute infection; and 4) false-positive core positivity. Unlike patients with chronic HBV infection and a positive viral load, who are at risk of HBV reactivation that may result in a clinically significant HBV flare, patients with IAHBC have an extremely low but probably not zero risk of HBV reactivation. This distinction has been shown in some retrospective studies, with no reactivation or very rare reactivation (<1%). However, current AASLD/IDSA guidelines state that “there are insufficient data to provide clear recommendations for the monitoring of HBV DNA among persons who test positive either for anti-HBc alone (isolated anti-HBc).” Given this uncertainty and limited data, in these cases, I err on the side of a more conservative monitoring approach. I do not delay initiation of DAA-based therapy but will counsel patients about the possible risk of reactivation, albeit low. Once treatment is initiated, I recommend monitoring with a hepatic function panel every four weeks during therapy and again at the SVR check. If the ALT increases at any point during therapy, I would then check HBV DNA and consider HBV therapy versus more intensive monitoring. Although this approach may be “overkill,” I believe it is safer and helps mitigate the patient’s (and provider’s) concern that HBV may reactivate during therapy.