The Clinical Efficacy and Adverse Effects of Entecavir plus Thymosin alpha-1 Combination Therapy versus Entecavir Monotherapy in HBV-related Cirrhosis: A Systematic Review and Meta-analysis

Abstract

Background Previous studies have demonstrated the benefits of thymosin alpha-1 (Tα1) in anti-virus, immunological enhancement and anti-inflammation. However, it is controversial about the efficacy and safety of entecavir (ETV) plus Tα1 combination therapy versus ETV monotherapy in cirrhosis patients with hepatitis B virus (HBV) infection. Objective The systematic review and meta-analysis of randomized clincal trials (RCTs) were performed to evaluate the efficacy and safety of ETV plus Tα1 compared with ETV monotherapy in HBV-related cirrhosis. Methods A systematic search was performed via PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), and Chinese Biological Medicine database (CBM). Relative risk (RR) and standardized mean difference (SMD) with a fixed- or random- effect model were calculated. Heterogeneity were assessed with the Cochrane Q-test and I 2 values. Results Seven RCTs involving 1144 subjects were included in the systematic review and meta-analysis. Compared with ETV monotherapy, ETV plus Tα1 combination therapy led to a higher complete response (RR = 1.18; 95% CI, 1.07 - 1.30). The HBV DNA undetectable rate and HBeAg loss rate of ETV plus Tα1 therapy for 24 weeks was higher than the ETV alone (RR = 1.91; 95% CI, 1.56 - 2.35; RR = 2.05; 95% CI, 1.62 - 2.60). However, after treatment for 48 and 52 weeks, there was no significantly different between the combination therapy and ETV monotherapy (RR = 1.07; 95% CI, 0.96 - 1.18; RR = 1.17; 95% CI, 0.89 - 1.55). In comparison with ETV alone, ETV plus Tα1 improved part of biochemical parameters and liver fibrosis. There was significant heterogeneity. In addition, The ETV plus Tα1 significantly reduced adverse events compared to ETV monotherapy (RR = 0.48; 95% CI, 0.24 - 0.95). Conclusions ETV plus Tα1 combination therapy might have a higher clinical response and a lower comprehensive adverse reaction rate in HBV-related cirrhosis patients compared with ETV monotherapy. Meanwhile, the whole patients included in this meta-analysis were from chinese mainland, so that more worldwide RCTs with a large sample size are needed to verify the current findings.