[Meta-analysis of the efficacy of the Fuzheng Huayu formula in the treatment of hepatitis B-associated liver fibrosis or cirrhosis]

Objective: To systematically evaluate the efficacy of Fuzheng Huayu (FZHY) tablets/capsules on hepatitis B-associated liver fibrosis or cirrhosis based on randomized controlled trials (RCTs) in order to provide more accurate evidence-based medicine for clinical rational drug use. Methods: Randomized controlled clinical trial research reports related to the treatment of hepatitis B-associated liver fibrosis or cirrhosis with FZHY published in SCI and statistical source core journals were retrieved from databases such as PubMed, Cochrane Library, and China National Knowledge Infrastructure (CNKI). RevMan 5.3 and Stata18.0 software were used to conduct a meta-analysis of the improvement rate of liver tissue inflammatory activity (HAI) and Ishak stage of liver fibrosis, the decrease value of liver stiffness measurement (LSM), hyaluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC-Ⅲ), type Ⅳ collagen (IV-C), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (Alb). The Q test was used for the heterogeneity test, with a random-effect model selected for large heterogeneity and a fixed-effect model for less heterogeneity. Results: A total of 852 articles were retrieved. Duplicate articles, non-RCT articles, non-SCI/statistical source/core journal articles, and other articles that did not meet the inclusion criteria were sequentially excluded. Finally, a total of 2 746 cases (1 382 cases in the FZHY group and 1 364 cases in the control group) were included from 25 studies. The results of statistical analysis showed that the improvement rates of HAI grade of liver inflammation were 75.56% (68/90) and 42.22% (38/90, P<0.001) in the FZHY group and the control group at 24-48 weeks of treatment, while the improvement rates of Ishak stage of liver fibrosis were 67.90% (110/162) and 40.91% (63/154, P=0.005), respectively. Compared with the control group (95%CI -5.10-1.77, P<0.001) the mean △LSM of the FZHY group decreased by 3.43 kPa (P<0.001)and 0.30 kPa (P=0.93) at 48 and 72 weeks of treatment. The standardized mean differences (SMDs) of △HA, △LN, △PC-Ⅲ and △Ⅳ-C were -1.12, -1.00, -0.89 and -1.10 (P<0.001) after 24 weeks of treatment between the FZHY group and the control group. The SMDs of △HA, △IV-C, △LN and △PC-Ⅲ were -1.13 (P=0.01), -1.51 (P<0.001), -0.53 (P=0.14) and -0.42 (P=0.19) after 48 weeks of treatment between the two groups. The △TBil, △ALT, △AST, and △ALB was -12.99 μmol/L (P=0.007), -36.91 U/L (P<0.001), -22.05 U/L (P=0.12), and 6.09 g/L (P=0.05) after 24 weeks of treatment between the two groups. The observation on indicators such as aspartate aminotransferase and platelet ratio index, fibrosis-4 index, and hepatocellular carcinoma incidence in current RCT studies remained deficient. Conclusion: FZHY can significantly improve the degree of histologic liver inflammation and fibrosis, LSM values, reduce serum liver fibrosis indexes, and serum bilirubin and transaminase levels in patients with hepatitis B-associated liver fibrosis or cirrhosis. Therefore, it is necessary to further explore the optimal course of FZHY and its long-term effects on the risk of complications of cirrhosis such as hepatocellular carcinoma, ascites, and esophageal varicose bleeding, through prospective large-sample multicenter real-world cohort studies.