Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy

Reactivation of hepatitis B virus (HBV) has been reported as a fatal complication following systemic chemotherapy or other immunosuppressive therapy. The risk of HBV reactivation differs according to both the patient's HBV infection status prior to systemic chemotherapy and the degree of immunosuppression due to chemotherapy. For establishing an optimal strategy for hepatitis prevention and treatment, it is necessary to understand the characteristics, the clinical course and the risk factors for HBV reactivation and to recognize the difference between hepatitis B surface antigen (HBsAg)-positive and -negative patients with HBV reactivation. Among the important viral risk factors, HBV-DNA level and HBV-related serum markers have been reported to be associated with HBV reactivation in addition to cccDNA, genotypes and gene mutations. Rituximab-plus-steroid combination chemotherapy has recently been identified as a host risk factor for HBV reactivation in hepatitis B core antibody (anti-HBc)-positive and/or hepatitis B surface antibody (anti-HBs) positive--but nonetheless HBsAg-negative--lymphoma patients. For these patients with resolved hepatitis B, preemptive therapy guided by serial HBV-DNA monitoring is a reasonable strategy to enable early diagnosis of HBV reactivation and initiation of antiviral therapy. In this review, we summarize the characteristics of HBV reactivation following rituximab-plus-steroid combination chemotherapy, mainly in HBsAg-negative lymphoma patients, and propose a strategy for managing HBV reactivation.