Prophylactic Effect of Lamivudine for Chemotherapy-Induced Hepatitis B Reactivation in Breast Cancer: A Meta-Analysis

<div><p>Background</p><p>Three strategies using lamivudine have been proposed to prevent chemotherapy-induced HBV (hepatitis B virus) reactivation in the clinical setting. The purpose of this meta-analysis is to evaluate the efficacy of the early preemptive strategy, deferred preemptive strategy and therapeutic strategy in patients with HBsAg-positive breast cancer during chemotherapy.</p><p>Methods</p><p>Clinical studies published from database inception until Nov 1, 2014, were included for analysis. The primary outcomes were overall survival, rate of chemotherapy disruption and virological and clinical reactivation. The secondary outcomes were the rates of HBV-related chemotherapy disruption, HBV-related mortality, YMDD mutations and withdrawal hepatitis.</p><p>Results</p><p>Four hundred and thirty patients in four studies that compared the early preemptive strategy with a therapeutic strategy were included. Application of early preemptive lamivudine was superior in reducing HBV recurrence (pooled OR: 0.12, 95% CI, 0.04 to 0.31, P< 0.0001), the incidence of HBV-related hepatitis (pooled OR: 0.13, 95% CI, 0.04 to 0.37, P< 0.0001) and the rate of chemotherapy disruption (pooled OR: 0.37, 95% CI, 0.23 to 0.60, P< 0.0001). In these two groups, no significant difference was found in overall mortality (P = 0.32), YMDD mutant rate (P = 0.13) or incidence of withdrawal hepatitis (P = 0.38). Of the two studies that compared the efficacy of an early and a deferred preemptive strategy, one showed that an early preemptive strategy significantly reduced the incidence of hepatitis (P = 0.046), whereas the other showed no significant difference (P = 0.7).</p><p>Conclusions</p><p>An early preemptive strategy is superior to a therapeutic strategy in decreasing the incidence of HBV reactivation, incidence of HBV-related hepatitis and rate of chemotherapy disruption in patients with breast cancer. A deferred preemptive strategy might be an alternative approach to controlling viral replication.</p></div

Schematic illustration of strategy to identified the subjects meeting the requirement in this study.

<p>Totally 492 records had been identified by literature searching. Based on abstracts, only 16 articles had been viewed as potential references for further assessment. After reviewing these articles in detail, only 6 articles had been selected for the meta-analysis.</p

The results of the trials.

<p>EP, early preemptive group; TP, therapeutic group; DP, deferred preemptive group; NA, non available; d, days; w, weeks; m, months</p><p>*, mean</p><p>The results of the trials.</p

The baseline characteristics of the studies.

<p>ALT, alanine aminotransferase; EP, early preemptive group; TP, therapeutic group; DP, deferred preemptive group, NA, non available</p><p>The baseline characteristics of the studies.</p

The proposed strategies to interfere with HBV during the chemotherapy in breast cancer patient.

<p>The phases of the patients had been divided into three stages; pre-chemotherapy, chemotherapy and post-chemotherapy. Lamivudine is given at the commencement of chemotherapy in early preemptive strategy and is given only after a significant rise of HBV DNA level in deferred preemptive strategy. If no early or deferred preemptive application of lamivudine had been given but the HBV DNA and ALT increased, the lamivudine applied to patients was used for therapeutic purpose.</p