Chinese herbal medicine combined with nucleotide analogues for compensated HBV-related cirrhosis: a systematic review of randomized controlled trials

Objective: To systematically evaluate the effectiveness and safety of Chinese herbal medicine (CHM) plus nucleotide analogues (NAs) for treating compensated HBV-related cirrhosis, the early stage of cirrhosis. Methods: PubMed, Cochrane library, China Network Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Database (VIP), Wan Fang Database and Sino-Med Database were searched. Randomized controlled trials (RCTs) and quasi-RCTs comparing NAs and NAs plus CHM therapy on patients with compensated HBV-related cirrhosis were included. Two reviewers independently extracted information and assessed the methodological quality of the trials. Different CHM herbal formulas used in the trials were considered. Primary meta-analysis was conducted when there were at least two trials comparing the same CHM formula. Results: Forty-five trials comprising 3497 participants were included. The quality of most of the trials was moderate or low. Twenty-six herbal formulations were identified. A meta-analysis was conducted for compound Biejia Ruangan (FFBJ), Dahuang Zhechong (DHZC), and Fuzheng Huayu (FZHY). The results of the subgroup analysis showed a beneficial effect of FFBJ plus entecavir (ETV), and DHZC plus adefovir dipivoxil (ADV) on hyaluronic acid (HA); FFBJ plus ADV on laminin (LN); and FZHY plus ADV on HA, LN, and precollagen type III (PC-III). The results from other studies suggested significant benefits of CHM plus NAs compared with NAs alone, except those on albumin (ALB). None of the trials evaluated the quality of life or reported severe adverse events. Conclusions: A positive effect was found for FFBJ plus ETV, DHZC plus ADV, and FZHY plus ADV on HA; FZHY plus ADV and FFBJ plus ADV on LN; and FZHY plus ADV on PCIII compared with the effects of NAs used alone