Immunosuppresive therapy, including steroids, cytotoxic agents, and tumor necrosis factor-α antagonists, is the cornerstone of treatment for patients with moderate-to-severe inflammatory bowel disease.1 The case reported by Zeitz et al.2 reiterated hepatitis B virus (HBV) reactivation as a potentially life-threatening complication in patients who received immunosuppressive therapy and the necessity of preventive antiviral therapy, consistent with our observation.3 Several issues should be addressed to optimize the preventive strategy in this setting.
The first issue is the optimal antiviral regimen and treatment duration. A significant proportion of patients with inflammatory bowel disease require long-term immunosuppressive therapy to maintain disease remission. Lamivudine is generally not recommended for long-term (more than 12 months) use because of the high incidence of drug-induced viral mutations.4 Agents with lower risk resistance, such as entecavir or tenofovir, should be considered first. According to the American Association for the Study of Liver Diseases guidelines, antiviral treatment should continue for 6 months after completion of immunosuppressive therapy or until endpoints for chronic HBV infection in immunocompetent patients have been reached.4
The second issue is the patient population at risk for HBV reactivation. Therapeutic monoclonal antibodies targeting the immune system may cause profound immunosuppression and may increase the risk of HBV reactivation not only in carriers of HBV surface antigen (HBsAg) but also in patients with “resolved” HBV infection.5, 6 In a retrospective analysis of lymphoma patients who were HBsAg-negative and anti-HBV core antigen (anti-HBc) positive, 5 of the 21 patients who received chemotherapy plus rituximab, an anti-CD20 antibody, developed hepatitis; all of them were attributed to HBV reactivation. The actual incidence of HBV reactivation may be even higher. Prospective studies to clarify the actual incidence and risk factors of HBV reactivation after immunotherapy in this patient population are necessary to define the optimal preventive strategy.