Preemptive Lamivudine Therapy Reduces Risk of Liver Disease Flares in Hepatitis B Patients Starting Cancer Chemotherapy 

By Liz Highleyman

Among people with chronic hepatitis B virus (HBV) infection, the disease may be inactive, but the virus may remain in the body and can reactivate if an individual’s immune system becomes suppressed, as often happens when patients undergo chemotherapy for cancer.

In a meta-analysis reported at the 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007), researchers assessed whether administering prophylactic lamivudine (Epivir-HBV) before commencing chemotherapy can prevent HBV reactivation and consequent morbidity and mortality in hepatitis B surface antigen (HBsAg) positive patients.

Investigators searched medical literature databases (MEDLINE, Ovid, Toxnet, Scopus, and Web of Science) for studies published through February 2007 that reported data allowing risk estimation of cancer chemotherapy-induced HBV reactivation in HBsAg positive patients receiving pre-emptive lamivudine compared with untreated control subjects. A 2-tailed P-value of < 0.05 was considered statistically significant. Comprehensive Meta-Analysis Software was used for the analysis.

 • 12 studies met predefined inclusion criteria, including adequate study population size (2 randomized controlled trials, 6 prospective studies, and 4 retrospective cohort studies).

• Of the 12 trials in the meta-analysis, 10 were conducted in East Asia, and 1 each in Turkey and Israel (all studies were in English except for 1 in Chinese).

• Overall, 214 patients in the studies received pre-emptive lamivudine, while 399 subjects serving as controls received either no lamivudine (3 studies) or deferred lamivudine (9 studies).

• The log odds ratios demonstrating risk reduction with pre-emptive lamivudine versus no pre-emptive lamivudine in HBsAg positive individuals undergoing cancer chemotherapy were as follows:

• 0.06 for HBV reactivation (95% CI 0.03-0.13);

• 0.07 for HBV-related liver inflammation (95% CI 0.04-0.14);

• 0.20 for liver failure (95% CI, 0.06-0.64);

• 0.21 for death (95% CI, 0.08-0.58).

• Combining results from all studies showed that the likelihood of HBV reactivation decreased from 35.6% to 2.8% with pre-emptive lamivudine (P < 0.0001).

• The rate of HBV-related hepatitis (liver inflammation) decreased from 32.3% to 2.8% (P < 0.0001).

• The rate of HBV-related liver failure decreased from 5.7% to 0.5 % (P = 0.0002).

• The risk of HBV-related death fell from 7.0% to 0.5 % (P < 0.0001).

Conclusion

“This meta-analysis demonstrated that pre-emptive lamivudine reduces the risk of HBV reactivation, HBV-related hepatitis, HBV-related acute liver failure, and HBV-related mortality by 16, 14, 5, and 5-fold, respectively,” the investigators concluded.

They estimated, based on this analysis, that “1 death can be prevented by treating 15 patients with pre-emptive lamivudine in this clinical setting.” Therefore, they recommended that, “HBsAg positive patients undergoing cancer chemotherapy warrant pre-emptive therapy with lamivudine.”

11/30/07

Reference
R Loomba, A Rowley, R Wesley, and others. Pre-emptive Lamivudine Reduces the Risk of Chemotherapy-Induced HBV-Related Morbidity and Mortality in HBsAg-Positive Cancer Patients: Meta-analysis. 58th Annual Meeting of the American Association for the Study of Liver Diseases. Boston, MA, November 2-6, 2007. Abstract 945.