Comparative effectiveness of glycyrrhizic acid preparations aimed at improving liver function of patients with chronic hepatitis B: A network meta-analysis of 53 randomized controlled trials

Background and objectives: Entecavir (ETV) has disadvantages, such as poor improvement in liver function, during the treatment of Chronic hepatitis B (CHB). Thus ETV is often used in clinical therapy with glycyrrhizic acid (GA) preparations. However, due to the lack of reliable and direct clinical studies, it remains controversial whether glycyrrhizic acid preparations have the best efficacy in CHB. Therefore, we aimed to compare and rank the different GA preparations in the treatment of CHB using network meta-analysis (NMA). Methods: We systematically searched MEDLINE, EMBASE, Cochrane Library, Web of Science, China national knowledge internet (CNKI), Wanfang, VIP, and SinoMed databases as of August 4, 2022. Literature was screened according to predefined inclusion and exclusion criteria to extract meaningful information. A Bayesian approach was used for random effects model network meta-analysis, and Stata 17 software was used for data analysis. Results: From 1074 papers, we included 53 relevant randomized clinical trials (RCTs). For the primary outcome, we used the overall effective rate in assessing the effectiveness of treatment for CHB (31 RCTs including 3007 patients): CGI, CGT, DGC and MgIGI significantly reduced the incidence of overall response compared to controls (RRs range from 1.16 to 1.24); SUCRA results showed that MgIGI was the best (SUCRA 0.923). In terms of secondary outcomes, we assessed the effect of treatment for CHB according to the level of reduction in ALT and AST: for ALT (37 RCTs including 3752 patients), CGI, CGT, DGC, DGI and MgIGI significantly improved liver function index compared to controls (MD range from 14.65 to 20.41); SUCRA results showed that CGI was the best (SUCRA 0.87); for AST, GI, CGT, DGC, DGI and MgIGI significantly improved liver function index compared to the control group (MD range from 17.46 to 24.42); SUCRA results showed that MgIGI was the best (SUCRA 0.871). Conclusion: In this study, we verified that the combination of GA and Entecavir is more effective than entecavir monotherapy in the treatment of hepatitis B. MgIGI and CGI showed clinically significant effects on liver function recovery compared with other GA preparations. MgIGI appeared to be the best choice among all GA preparations for the treatment of CHB. Our study provides some references for the treatment of CHB.