Peng Dan, Xing Hai-Yan, Li Chen, Wang Xian-Feng, Hou Min, Li Bin, Chen Jian-Hong
Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, 400042, China.
BMC Gastroenterol. 2020 Oct 19;20(1):348. doi: 10.1186/s12876-020-01477-8.
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.
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 I values.
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).
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.
既往研究已证实胸腺肽α1（Tα1）在抗病毒、免疫增强及抗炎方面的益处。然而，对于乙型肝炎病毒（HBV）感染的肝硬化患者，恩替卡韦（ETV）联合Tα1治疗与ETV单药治疗的疗效及安全性存在争议。
进行随机临床试验（RCT）的系统评价和荟萃分析，以评估ETV联合Tα1治疗与ETV单药治疗在HBV相关肝硬化患者中的疗效和安全性。通过PubMed、Web of Science、Cochrane对照试验中心注册库（CENTRAL）、EMBASE、中国知网（CNKI）、中文科技期刊数据库（VIP）和中国生物医学数据库（CBM）进行系统文献检索。采用固定效应或随机效应模型计算相对危险度（RR）和标准化均数差（SMD）。通过Cochrane Q检验和I²值评估异质性。
系统评价和荟萃分析纳入了7项涉及1144名受试者的RCT。与ETV单药治疗相比，ETV联合Tα1治疗导致更高的完全缓解率（RR = 1.18；95%CI，1.07 - 1.30）。治疗24周后，ETV联合Tα1组的HBV DNA不可检测率和HBeAg血清学转换率高于ETV单药组（RR = 1.91；95%CI，1.56 - 2.35；RR = 2.05；95%CI，1.62 - 2.60）。然而，治疗48周和52周后，联合治疗与ETV单药治疗之间无显著差异（RR = 1.07；95%CI，0.96 - 1.18；RR = 1.17；95%CI，0.89 - 1.55）。治疗第52周时，ETV联合Tα1组的HBsAg消失率与ETV单药组无显著差异（RR = 1.03；95%CI，0.15 - 7.26）。与ETV单药相比，ETV联合Tα1可使一些生化指标和肝纤维化明显改善，且存在显著异质性。此外，与ETV单药相比，ETV联合Tα1显著减少了不良事件的发生数量（RR = 0.48；95%CI，0.24 - 0.95）。
与ETV单药治疗相比，ETV联合Tα1可能使HBV相关肝硬化患者获得更高的临床缓解率和更低的综合不良反应率。然而，本荟萃分析纳入的全部患者均来自中国大陆，因此需要更多全球范围内样本量更大的RCT来验证当前研究结果。
