The efficacy and safety of Chinese patent medicine LWWL combined with nucleoside/nucleotide analogues in treatment of chronic hepatitis B: A systematic review and meta-analysis

Background: HBV infection is still one of the serious public health problems in the world. NAs as the first line drugs effectively inhibit viral replication, whereas the suppressive effects are much weaker on HBV antigen expression. Chinese patent medicine Liuweiwuling tablet (LWWL) has been used for chronic hepatitis B (CHB) patients for more than 10 years as an adjuvant treatment. Objective. This study aimed to assess the efficacy and safety of LWWL combined with NAs in treating CHB by meta-analysis. Methods. Systematic searches for randomized controlled trials (RCT) were conducted in four databases (up to December 2020) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as weight mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcomes were negative conversion rate of serum HBV DNA and HBeAg. The secondary outcomes were improvement of liver function including ALT and AST, and adverse drug reactions. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias. Results. A total of 201 potentially relevant publications were identified, and 20 RCTs were eligible for inclusion. For the negative rate of HBV DNA (OR ​= ​2, 95%CI:1.64–2.45, P ＜0.05) and HBeAg (OR ​= ​1.83, 95%CI:1.46–2.30, P＜0.05), there were both statically significant benefit in favor of LWWL combined with NAs. In addition, Meta-analysis also showed that LWWL combined with NAs significantly reduced ALT (WMD ​= ​−17.73, 95%CI: 21.37∼-14.09, P ​< ​0.01), AST (MD ​= ​-23.49, 95%CI: −30.52∼-16.45, P ​< ​0.05), and increased the normalization rate of ALT (OR ​= ​3.89, 95%CI:2.82–5.36, P ​< ​0.01). Conclusion. The negative conversion rates of HBV DNA, HBeAg, and improvement of liver function in patients treated with LWWL combined with NAs were significantly higher than those treated with NAs alone, and no serious ADRs were identified. This work provides a reference to the evidence, for the beneficial effects of LWWL combined with NAs in treating CHB.