Gastroenterology

Gastroenterology

Volume 125, Issue 6, December 2003, Pages 1742-1749
Gastroenterology

Clinical-liver, pancreas, and biliary tract
Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy

https://doi.org/10.1053/j.gastro.2003.09.026Get rights and content

Abstract

Background & Aims: Hepatitis B virus reactivation is a serious cause of morbidity and mortality in hepatitis B surface antigen-positive patients treated with chemotherapy. We compared the efficacy of early and deferred preemptive lamivudine therapy in reducing the incidence of hepatitis due to hepatitis B virus reactivation in hepatitis B surface antigen-positive lymphoma patients treated with chemotherapy.Methods: Thirty consecutive hepatitis B surface antigen-positive lymphoma patients undergoing intensive chemotherapy were randomized (1:1) to receive lamivudine 100 mg daily 1 week before chemotherapy (group 1) or to have this treatment deferred until there was serological evidence of hepatitis B virus reactivation on the basis of serial 2-week-interval serum hepatitis B virus DNA monitoring by a Digene Hybrid Capture II assay (group 2).Results: Eight (53%) patients in group 2 and none in group 1 had hepatitis B virus virological reactivation after chemotherapy (P = 0.002). Seven patients in group 2 still had hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Survival free from hepatitis due to hepatitis B virus reactivation in group 1 patients was significantly longer than that in group 2 (P = 0.002 on the log-rank test). The median onset of hepatitis B virus reactivation in these patients was 16 weeks (range, 4–36 weeks) after the initiation of chemotherapy. Three (13%) of the 23 patients treated with lamivudine had hepatitis B virus-related hepatitis after lamivudine withdrawal.Conclusions: Lamivudine should be considered preemptively before or at the initiation of chemotherapy for all hepatitis B surface antigen-positive lymphoma patients undergoing intense chemotherapy.

Section snippets

Patients studied

From February 2001 to March 2003, 402 adult lymphoma patients were treated with high-dose chemotherapy at Queen Mary Hospital and Queen Elizabeth Hospital, Hong Kong Special Administrative Region, China. In accordance with our standard protocols for lymphoma patients treated with chemotherapy, all patients were screened for HBsAG, hepatitis B surface antibody, hepatitis C virus antibody (anti-HCV), and human immunodeficiency virus antibody before chemotherapy. For all HBsAG-positive patients,

Patient characteristics

There were no statistical differences between the 2 groups in terms of sex, age, underlying hematologic diseases, baseline serum ALT, bilirubin, HBeAG status, serum HBV DNA level (by Digene Hybrid Capture II assay), HBV genotype, or the presence of (A1896) and basal core promoter (T1762/A1764) variants (Table 1).

Hepatitis after chemotherapy

Twenty-nine patients survived the entire period of the study: there was 1 death due to uncontrolled lymphoma and disseminated sepsis in group 2. Two patients in group 1 received bone

Discussion

Effective anti-HBV nucleoside analogues, such as lamivudine, are now available for treatment of hepatitis due to HBV reactivation in HBsAG-positive subjects undergoing intense chemotherapy.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 The optimal time for its initiation remains uncertain.23 The initiation of antiviral treatment only after there are major biochemical abnormalities is not entirely satisfactory. This may not be effective in reducing liver injury by this time,8, 10 because

References (39)

  • G.K.K. Lau et al.

    High HBV DNA viral load is the most significant risk factor for hepatitis B reactivation in hepatitis B surface antigen positive patients treated with autologous hematopoietic cell transplantation

    Blood

    (2002)
  • A.S. Lok et al.

    Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study

    Gastroenterology

    (1991)
  • J.M. Pawlotsky

    Molecular diagnosis of viral hepatitis

    Gastroenterology

    (2002)
  • R. Perrillo et al.

    Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

    Hepatology

    (2000)
  • R. Liang et al.

    Chemotherapy and bone marrow transplantation for cancer patients who are also chronic hepatitis B carriersa review of the problem

    J Clin Oncol

    (1999)
  • L. Xunrong et al.

    Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy—pathogenesis and management

    Rev Med Virol

    (2001)
  • J.H. Hoofnagle et al.

    Reactivation of chronic hepatitis B virus infection by cancer chemotherapy

    Ann Intern Med

    (1982)
  • C.M. Maguire et al.

    Case reportlamivudine therapy for submassive hepatic necrosis due to reactivation of hepatitis B following chemotherapy

    J Gastroenterol Hepatol

    (1999)
  • W. Yeo et al.

    Lamivudine in the treatment of hepatitis B virus reactivation during cytotoxic chemotherapy

    J Med Virol

    (1999)
  • Supported in part by Glaxo-SmithKline Pharmaceuticals (GSK NUC30939). This project was supported by a grant from the Cheng Si-yuan (China-International) Hepatitis Research Foundation (to the University of Hong Kong), a China National 973 research grant (Grant 1999 054105 [to G.K.K.L.]), an ear-marked grant from the Hong Kong Research Grant Council, and a grant from the University Research Committee (to R.L.).

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