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

Abstract

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 liver injury 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 reduced the incidence of liver injury compared to controls (RRs 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 reduced the incidence of liver injury compared to the control group (RRs 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 all GA preparations were influential in the treatment of hepatitis B-induced liver injury through a reticulated meta-analysis. 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 guidance for the treatment of hepatitis B-induced liver injury with GA agents, but further clinical trials are needed to confirm our findings.

Note:
Funding declaration: This work was supported by the Health Commission of Hunan Provincial (No. 202113012480). It was also supported by the International Research Center for Precision Medicine, Transformative Technology, and Software Services, Hunan, China.

Conflicts of Interest: None

Trial Registration: The study was registered on PROSPERO under registration number CRD42022351351.

Keywords: Glycyrrhizic acid preparations, treatment, Network meta-analysis, Chronic hepatitis B, Entecavir