Effectiveness of Chinese medicines in treating chronic liver diseases

Chronic liver diseases mainly indicate liver fibrosis (LF) and cirrhosis. Advanced liver fibrosis may result in fatal complications including liver cirrhosis and hepatocellular carcinoma (HCC). LF is suggested to be reversible but lack of conclusive evidence on effective and safe therapy currently. Transarterial chemoembolization (TACE) is the primary option with severe adverse effects for unresectable HCC patients because most HCC are detected at a very advanced stage. Meanwhile, Chinese medicine (CM) has been considered as an alternative therapy for LF and HCC because of its low cost and high safety. This thesis aims to (1) conduct comprehensive meta-analysis and systematic reviews of randomized controlled clinical trials (RCTs) to critically evaluate the efficacy and safety of CMs in treating LF and unresectable HCC; (2) explore its potential as an evidence-based alternative or adjuvant therapy for LF or HCC. The studies were conducted according to the Cochrane guidelines for systematic review and PRISMA statement. Comprehensive databases were used including MEDLINE, AMED, EMBASE, The Cochrane Library, CINAHL Plus, PubMed, CNKI, TCMOnline, Chinese Biomedical Literature Database, WanFang Database, and Chinese Medical Current Contents. The bibliographies of identified studies were also screened. RCTs examining the effects of CMs in treating LF patients or CMs combined with TACE in treating unresectable HCC patients were included. Inverse-variance random effects model was used to calculate the mean difference (MD) with 95% confidence intervals (CIs) in the LF systematic review when both risk ratios (RRs) and MD were used in the HCC review. Heterogeneity and publication bias were estimated. The methodological quality of included RCTs were assessed using the Cochrane ‘risk of bias’ assessment. Twenty-three RCTs (number of patients=2123) were eligible for LF review and 67 RCTs (number of patients=5211) for HCC review. For LF review, 15 RCTs were classified as high quality. Significant reduction in LF biomarkers including HA, LN, PC-III and IV-C was found in CHM alone and CHM plus Western medicine group when compared with Western medicine alone. For HCC review, 26 RCTs were ranked as high quality. Significant improvement in tumor response, survival, immunity and quality of life, and decrease of TACE toxicity were found in the CMs plus TACE compared with TACE alone. No clinically significant CMassociated adverse events were observed for both LF and HCC trials. The results of both LF and HCC reviews have shown that CMs may exert antifibrotic and anti-HCC properties. The findings indicate that CMs can be considered as a potential alternative therapy for LF or HCC. Due to the low methodological quality and significant heterogeneity, RCTs with large sample size, long-term follow-up, and standard research protocols compliance with CONSORT guidelines are needed for further investigation.published_or_final_versionChinese MedicineDoctoralDoctor of Philosoph