title: Effect of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in lymphoma: a meta-analysis of published clinical trials and a decision tree addressing prolonged prophylaxis and maintenance.
abstract: Lamivudine prophylaxis is an effective strategy in HbSAg-positive patients receiving cancer chemotherapy. Recent data indicate that a lamividune-prophylaxis strategy results in a decrease of hepatitis B virus (HBV) reactivation rates, though its effect on HBV-mortality remains equivocal. This report evaluates the benefits from this strategy among lymphoma patients and develops a management approach for patients with prolonged immunosuppression. A Medline search was conducted to retrieve published trials on HBsAg-positive lymphoma patients receiving prophylactic lamivudine during chemotherapy. Basic inclusion criterion was to report HBV-reactivation rates with and without lamivudine prophylaxis. A meta-analysis of the risk of HBV-reactivation and HBV-related mortality was conducted, and the pooled effect was calculated as risk ratio (RR). We found that lamivudine prophylaxis is associated with a significant reduction in hepatitis B virus reactivation (RR 0.21, 95%CI 0.13-0.35) and a trend in reducing HBV-related mortality (RR 0.68, 95%CI 0.19-2.49). In order to study the long-term effects of anti-HBV prophylaxis when prolonged immunosuppression is needed, we used our findings to model a decision tree. Overall survival was the main outcome used in the analysis. Rituximab maintenance in B-cell lymphomas was used as a paradigm of prolonged immunosuppression. We found that extended anti-HBV prophylaxis can improve survival rates by 2.4% in HBsAg-positive patients. If 1,000 HBsAg-positive lymphoma patients receive prophylaxis, one will die from hepatitis B virus reactivation versus 25/1,000 if no prophylaxis is administered. This effect is probably mediated through a reduction of hepatitis B virus reactivation and HBV-related mortality. The ideal antiviral agent needs to be determined.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Panayiotis D
authors.initials: PD
authors.lastname: Ziakas
authors.forename: Petros
authors.initials: P
authors.lastname: Karsaliakos
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003661:Decision Support Techniques; D006509:Hepatitis B / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D019259:Lamivudine / Q000494:pharmacology*; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D008954:Models, Biological; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine