Clinical

Hepatitis B reactivation possible after chemotherapy

Last Updated: 2005-11-02 13:30:12 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In hepatitis B (HBV) infected patients receiving pre-emptive lamivudine treatment before they undergo cancer chemotherapy, reactivation of the virus is possible once lamivudine therapy is withdrawn, researchers in Hong Kong report. They recommend a more prolonged course of antiviral therapy in patients with a high pre-chemotherapy serum HBV DNA level or who are positive for HBV e antigen.

Liver damage due to HBV reaction is a two-stage process, Dr. C-K Hui and associates note in their report, published in the November 5th issue of Gut. Increased viral replication during cytotoxic therapy is followed by rapid immune-mediated destruction of HBV-infected hepatocytes.

That is why a short course of lamivudine is recommended while HBV-infected patients undergo cytotoxic or immunosuppressive therapy. Current recommendations call for lamivudine to be started 1 week before chemotherapy and continued for at least 6 weeks afterwards, although the optimal duration has yet to be defined.

To assess the problem of HBV rebound, Dr. Hui and colleagues prospectively followed 46 HBV-positive patients treated with cytotoxic chemotherapy for a hematological malignancy at Queen Mary Hospital. Lamivudine, commenced 1 week prior to starting chemotherapy, was continued for at least 3 months after discontinuing chemotherapy and until the total white cell count had normalized.

During follow-up, 11 patients developed HBV reactivation between 6 and 33 months after discontinuing lamivudine. Although lamivudine was resumed in all 11 cases, three developed fulminant hepatic failure and one died.

Factors predictive of HBV reactivation were HBV DNA levels of 10,000 copies/mL or more, and a positive HBV e antigen test prior to chemotherapy.

The authors recommend that all patients undergoing intense cytotoxic chemotherapy be screened for HBV surface antigen, and those who are positive be placed on preemptive lamivudine therapy.

Dr. Hui's group notes that the antiviral drug can be withdrawn in HBV e antigen-negative patients with low pre-chemotherapy serum HBV DNA levels once white cell counts have returned to normal. They still advise close monitoring of serum HBV DNA and alanine amino transaminase levels every 4 weeks for the next 12 months, with lamivudine resumed if a 10-fold increase in HBV DNA is observed.

However, for patients positive for HBV e antigen or with a high pre-chemotherapy HBV DNA, lamivudine therapy should be prolonged to reduce the chance of HBV reactivation.

Gut 2005;54:1597-1603.