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

Abstract

BackgroundThree 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.MethodsClinical 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.ResultsFour 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).ConclusionsAn 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.

Prophylactic effect of lamivudine on chemotherapy-induced hepatitis B virus reactivation in patients with solid tumour: A meta-analysis

“…Several inconsistencies were found in the incidence of HBV reactivation, HBV-associated hepatitis and disruption of chemotherapy between the prophylactic lamivudine group and non-prophylaxis group. As for patients with solid tumours, three meta-analysis Tang et al, 2015;Zheng et al, 2013) have investigated the efficacy of prophylactic lamivudine in patients with breast cancer and another two (Hicks LK et al, 2016;Paul et al, 2016) This study demonstrated that prophylactic lamivudine in HBsAgseropositive patient with solid tumours undergoing chemotherapy effectively reduces HBV reactivation (p < .00001) and its consequent negative outcomes, including hepatitis (p < .00001), disruption of chemotherapy (p = .01) and mortality (p = .08). However, one prospective RCT (Long et al, 2011) suggested the incidence of hepatitis, chemotherapy disruptions and overall death between the prophylactic lamivudine group and non-prophylaxis group were not statistically different.…”

“…However, these articles either focused on haematological tumours or mixed solid and haematological malignancy together. As for patients with solid tumours, three meta-analysis Tang et al, 2015;Zheng et al, 2013) have investigated the efficacy of prophylactic lamivudine in patients with breast cancer and another two (Hicks LK et al, 2016;Paul et al, 2016) This study demonstrated that prophylactic lamivudine in HBsAgseropositive patient with solid tumours undergoing chemotherapy effectively reduces HBV reactivation (p < .00001) and its consequent negative outcomes, including hepatitis (p < .00001), disruption of chemotherapy (p = .01) and mortality (p = .08). A total of 10 HBV-related deaths were reported in some of our incorporated studies (Dai et al, 2004;Lee et al, 2012;Lim et al, 2002;Lin et al, 2014;Yeo et al, 2005) with mortalities ranging from 0% to 20% and all the deaths came from the group without lamivudine…”

“…Currently, newer NAs for antiviral treatment have been widely researched and applied, such as entecavir, adefovir, telbivudine and tenofovir. As the most widely studied nucleoside reverse transcriptase inhibitor for the last decade, lamivudine can effectively decrease viral load in serum, thus improving the clinical outcomes with few adverse effects for HBsAg-positive patients undergoing chemotherapy (Kohrt, Ouyang, & Keeffe, 2006;Loomba et al, 2008;Tang et al, 2015). While a few meta-analyses (Hicks LK et al, 2016;Paul et al, 2016) have investigated the effectiveness of prophylactic NAs prior to chemotherapy in the setting of solid tumours, none of them managed to make a solo probe into the prophylactic effects of lamivudine.…”

“…While a few meta-analyses (Hicks LK et al, 2016;Paul et al, 2016) have investigated the effectiveness of prophylactic NAs prior to chemotherapy in the setting of solid tumours, none of them managed to make a solo probe into the prophylactic effects of lamivudine. As the most widely studied nucleoside reverse transcriptase inhibitor for the last decade, lamivudine can effectively decrease viral load in serum, thus improving the clinical outcomes with few adverse effects for HBsAg-positive patients undergoing chemotherapy (Kohrt, Ouyang, & Keeffe, 2006;Loomba et al, 2008;Tang et al, 2015). Therefore, we conduct a meta-analysis to access the efficacy of prophylactic lamivudine on preventing HBV reactivation and its related negative outcomes such as hepatitis, disruption of chemotherapy and mortality in solid tumour patients with chronic HBV infection receiving systemic chemotherapy.…”

Hepatitis B virus reactivation in breast cancer patients undergoing chemotherapy: A review and meta‐analysis of prophylaxis management

“…According to recent studies, the intervention strategies can be divided into as follows: (i) prophylactic therapy (early pre‐emptive therapy): use of antivirals prior to the start of chemotherapy; (ii) pre‐emptive therapy (deferred pre‐emptive therapy): test HBV DNA regularly and use antivirals immediately when HBV DNA rises above baseline and ALT level is still within normal limits; (iii) therapeutic intervention: use antivirals when ALT level rises . Recent meta‐analyses have addressed the efficacy of pre‐emptive therapy for HBV reactivation in patients with breast cancer . We also performed a meta‐analysis to assess the benefits of prophylactic lamivudine for reactivation by adding more data.…”