Systematic Review: The Effect of Preventive Lamivudine on Hepatitis B Reactivation during Chemotherapy

1 April 2008 | Volume 148 Issue 7 | Pages 519-528

Background: Lamivudine is increasingly being used to prevent hepatitis B reactivation in patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy.

Purpose: To determine whether preventive lamivudine reduces chemotherapy-induced hepatitis B virus (HBV)–related morbidity and mortality in patients with cancer who test positive for HBsAg.

Data Sources: MEDLINE, Ovid MEDLINE, TOXNET, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in all languages until June 2007.

Study Selection: Clinical trials and cohort studies that reported the efficacy of preventive lamivudine versus control on HBV reactivation in patients who tested positive for HBsAg and were receiving chemotherapy were included. Additional requirements included minimum sample size (>5 participants per treatment group) and reported HBV-related morbidity and mortality data.

Data Extraction: Two investigators independently did literature searches and data extraction, and 2 other investigators independently confirmed study eligibility and data retrieval.

Data Synthesis: Fourteen studies (2 randomized, controlled trials; 8 prospective cohort studies; and 4 retrospective cohort studies) met the predefined criteria for analysis. There were 275 patients in the preventive lamivudine group and 475 control participants for the primary end point of HBV reactivation. With preventive lamivudine, the relative risk for both HBV reactivation and HBV-related hepatitis ranged from 0.00 to 0.21. None of the patients in the preventive lamivudine group developed HBV-related hepatic failure (0 of 108 patients vs. 21 of 162 patients), and only 4 deaths were attributable to HBV (4 of 208 patients vs. 27 of 394 patients) in the preventive lamivudine group. Lamivudine was well tolerated, and no adverse effects were noted.

Limitations: The studies included in the meta-analysis did not consistently report all of the outcomes of interest. Sample sizes were small and only 2 studies had a randomized, controlled design.

Conclusion: Preventive therapy with lamivudine for patients who test positive for HBsAg and are undergoing chemotherapy may reduce the risk for HBV reactivation and HBV-associated morbidity and mortality.

Editors' Notes Context Does lamivudine prevent hepatitis B virus (HBV) reactivation among patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy? Contribution This systematic review of 14 studies found that, compared with no preventive lamivudine, lamivudine reduced HBV reactivation, HBV-related hepatitis, and HBV-related hepatic failure. Caution Studies were small and heterogeneous. Only 2 were randomized trials, and none compared lamivudine with other, newer anti-HBV agents. Implication Preventive lamivudine may reduce risk for HBV reactivation and associated death in HBsAg-positive patients with cancer who are undergoing chemotherapy. —The Editors

 

Author and Article Information

From National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland.

Acknowledgment: The authors thank Jordan Feld, MD, who provided feedback on the study results.

Grant Support: By the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases and the Clinical Center, National Institutes of Health.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Rohit Loomba, MBBS, MHSc, CRC-4-5722, MSC-1614, 10 Center Drive, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892; e-mail, roloomba{at}ucsd.edu.

Current Author Addresses: Dr. Loomba: Division of Gastroenterology, Department of Medicine, University of California at San Diego, UC 303, MC063, 9500 Gilman Drive, La Jolla, CA 92093.

Drs. Rowley and Pucino: Pharmacy Department, Clinical Center, Building 10, Room 1N-257, 10 Center Drive, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892.

Dr. Wesley: Hospital Epidemiology, Clinical Center, Building 10, Room 2N-228B, 10 Center Drive, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892.

Dr. Liang: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Building 10/9B-16, MSC-1800, 10 Center Drive, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892.

Dr. Hoofnagle: Liver Diseases Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Building 31/9A-27, MSC-1800, 31 Center Drive, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892.

Dr. Csako: Department of Laboratory Medicine, Clinical Center, Building 10, Room 2C-407, 10 Center Drive, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892.