ABSTRACT: BACKGROUND:Previous studies have demonstrated the benefits of thymosin alpha-1 (T?1) in anti-virus, immunological enhancement and anti-inflammation. However, it is controversial about the efficacy and safety of entecavir (ETV) plus T?1 combination therapy versus ETV monotherapy in cirrhotic patients with hepatitis B virus (HBV) infection. METHODS:The systematic review and meta-analysis of randomized clinical trials (RCTs) were performed to evaluate the efficacy and safety of ETV plus T?1 combination therapy versus ETV monotherapy in HBV-related patients with cirrhosis. We performed a systematic literature search 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 was assessed through a Cochrane Q-test and I2 values. RESULTS:Seven RCTs involving 1144 subjects were included in the systematic review and meta-analysis. Compared with ETV monotherapy, ETV plus T?1 combination therapy led to a higher complete response (RR?=?1.18; 95% CI, 1.07-1.30). In post treatment for 24?weeks, the HBV DNA undetectable rate and HBeAg loss rate were higher in ETV plus T?1 group than in ETV alone group (RR?=?1.91; 95% CI, 1.56-2.35; RR?=?2.05; 95% CI, 1.62-2.60). However, after 48 and 52?weeks of treatment, there was no significant difference 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). At week 52 of treatment, the HBsAg loss rate of ETV plus T?1 group was no significance with that of ETV alone group (RR?=?1.03; 95% CI, 0.15-7.26). In comparison with ETV alone, the some biochemical parameters and liver fibrosis were obviously improved by ETV plus T?1, and there was significant heterogeneity. In addition, the number of adverse events was significantly reduced by ETV plus T?1, compared to ETV alone (RR?=?0.48; 95% CI, 0.24-0.95). CONCLUSIONS:ETV plus T?1 might lead to a higher clinical response and a lower comprehensive adverse reaction rate in HBV-related patients with cirrhosis, compared to ETV alone. However, the whole patients included in this meta-analysis were from Chinese mainland, so that more worldwide RCTs with a larger sample size are needed to verify the current findings.
