Doxorubicin activates hepatitis B virus (HBV) replication in HBV-harboring hepatoblastoma cells. A possible novel mechanism of HBV reactivation in HBV carriers receiving systemic chemotherapy

Abstract

Background: Reactivation of HBV replication is a clinically significant complication in HBV(+) patients receiving chemotherapy. We recently found that nearly half of the HBV reactivation in lymphoma patients occurred within 2 weeks of the first dose of chemotherapy. We hypothesized that mechanisms other than immunosuppression, such as direct stimulation of HBV replication by anticancer drugs, might be involved in this type of HBV reactivation. Materials and Methods: 2.2.15 cells, which secrete HBV particles constitutively, were used in the experiments. Real-time quantitative polymerase chain reaction was used to quantitate HBV DNA, and microparticle enzyme immunoassay to measure HBV surface antigen (HBsAg). Results: HBV DNA secretion in culture medium was dose- dependency increased by doxorubicin, one of the most commonly used anticancer drugs for lymphoma. One-hour exposure of cells to 1 μM doxorubicin induced a 15.4±5.9-fold and a 3.05±0.09-fold increase of HBV DNA and HBsAg on the 4th culture day, respectively. Lamivudine suppressed the doxorubicin-induced increase of HBV DNA. Conclusion: Our data suggest that cytotoxic agents may stimulate the replication of HBV and thereby contribute to the reactivation of HBV during systemic chemotherapy. Importantly, this adverse effect of cytotoxic agents may be preventable by co-administration of lamivudine.