Prophylactic Lamivudine Reduces HBV Flares During Chemotherapy

In patients with chronic hepatitis B virus (HBV) infection and breast cancer, prophylactic lamivudine before chemotherapy reduces the risk for HBV reactivation and interruption of chemotherapy, according to a study published in the Journal of Viral Hepatitis.

“Breast cancer patients with coexisting chronic HBV infection have a high risk of HBV reactivation and hepatocyte necrosis, which may result in severe or fulminant liver failure during chemotherapy,” Chang Gong, MD, PhD, from Sun Yat-sen Memorial Hospital, Guangzhou, China, told Infectious Disease Advisor.

Although severe liver failure is potentially fatal, HBV flares of lesser severity may lead to interruptions in chemotherapy, which is associated with poor prognosis. Data suggest that prophylactic treatment with antiviral agents before chemotherapy may decrease the risk for HBV reactivation during chemotherapy in this population.

A team of researchers led by Dr Gong and Yubao Zheng, MD, PhD, from Third Affiliated Hospital of Sun Yat-sen University in China, conducted a meta-analysis to evaluate the efficacy of lamivudine prophylaxis in patients with positive hepatitis B surface antigen status and breast cancer requiring chemotherapy.

A total of 709 patients from 8 studies were included for analysis. In 6 studies that evaluated HBV reactivation during chemotherapy, patients receiving lamivudine prophylaxis (n = 232) were significantly less likely to have HBV flares than patients not receiving prophylaxis (n = 387; odds ratio [OR], 0.15; P <.00001).

Chemotherapy was disrupted because of HBV reactivation less often in patients undergoing prophylactic treatment (n = 228) compared with patients not receiving lamivudine (n = 292) in 6 studies (OR, 0.17; P =.0002).

The risk of developing tyrosine-methionine-aspartate-aspartate (YMDD) mutations, which confer resistance to lamivudine therapy, was significantly higher in patients receiving prophylaxis than in patients not receiving prophylaxis (OR, 6.33; P =.05). However, YMDD mutations occurred in only 4 of 572 patients overall.

Although lamivudine prophylaxis may reduce the risk for HBV flares during breast cancer chemotherapy, Dr Gong noted that the high rates of YMDD mutations observed with lamivudine use may no longer make this agent an attractive first-line option for prophylaxis. Antiviral agents entecavir and tenofovir, which are associated with a lower risk of resistance, may be considered instead.

“Prophylactic antiviral management plays a prerequisite ‘escort’ role for these patients, not only to reduce the frequency of chemotherapy interruption due to HBV reactivation but also to [ensure] the completion of the chemotherapy or radiotherapy schedule,” Dr Gong said.

However, the best approach to prophylactic antiviral therapy is not clearly established, as most of the evidence for antiviral prophylaxis is derived from retrospective studies. “Large, multicenter prospective studies are required to verify the efficacy of different prophylactic anti-HBV regimens in breast cancer patients with coexisting HBV infection,” Dr Gong concluded.

Reference

Liu Z, Jiang L, Liang G, Song E, Zheng Y, Gong C. Hepatitis B virus reactivation in breast cancer patients undergoing chemotherapy: a review and meta-analysis of prophylaxis management [Published online January 10, 2017]. J Viral Hepat. doi: 10.1111/jvh.12672