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 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 Tα1 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 Tα1 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 Tα1 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 Tα1 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 Tα1, and there was significant heterogeneity. In addition, the number of adverse events was significantly reduced by ETV plus Tα1, compared to ETV alone (RR = 0.48; 95% CI, 0.24–0.95). Conclusions ETV plus Tα1 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.

Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus

“…95 Combination treatment with ETV and thymosin alpha-1 did not significantly improve the rate of undetectable HBV DNA or the rate of HBsAg loss after 52 weeks compared to mono ETV treatment. 105 However, in a phase 2 clinical trial, combination treatment with a NA and selgantolimod showed a 5% rate of HBsAg loss after 24 weeks. 81 Similarly, HBsAg loss was observed in 25% of patients at 4 weeks of treatment in a phase 2a clinical trial of NA and GSK3228836 combination treatment.…”

“…Combination treatment with a NA and GS-4774 did not further reduce HBsAg levels compared to monotreatment with NA in a phase 2 clinical trial [ 94 ]. Combination treatment with ETV and thymosin alpha-1 did not significantly improve the rate of undetectable HBV DNA or the rate of HBsAg loss after 52 weeks compared to mono ETV treatment [ 104 ]. However, in a phase 2 clinical trial, combination treatment with a NA and selgantolimod showed a 5% rate of HBsAg loss after 24 weeks [ 80 ].…”

Molecular Mechanism of the Regulatory Effect of Schisandrol A on the Immune Function of Mice Based on a Transcription Factor Regulatory Network

“…Due to the close correlation of immune system function with human health; infections, inflammatory diseases, and even cancers will easily occur if the immune system is abnormal. At present, the pathogenesis of immune system abnormalities remains unclear, and chemical synthetic drugs, human or animal immune products, and microbial drugs are mainly used for the treatment of abnormalities in the clinic, but these drugs have different degrees of side effects ( Peng et al, 2020 ; Vavla et al, 2020 ). Therefore, researchers have begun to look for immunomodulatory substances from safer natural products and their extracts.…”