Published online 19 May 2009
Haematologica, Vol 94, Issue 7, 998-1005 doi:10.3324/haematol.2009.005819
Copyright © 2009 by Ferrata Storti Foundation
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Infectious Disorders

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

Panayiotis D. Ziakas1,2, Petros Karsaliakos2, Eleftherios Mylonakis1

1 Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA and
2 Hygeia Diagnostic & Therapeutic Center, Athens, Greece

Correspondence: Panayiotis D. Ziakas, M.D., Ph.D., Hygeia Diagnostic & Therapeutic Center, 4 Erythrou Stavrou St, Athens, 15123, Greece. E-mail:zpanos{at}otenet.gr

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.

Key words: lymphoma, hepatitis B, reactivation, lamivudine, prophylaxis, mortality.




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