Abstract: We included 77 randomised clinical trials, which included 6753 participants with fatty liver disease. The risks of bias (overestimation of benefits and underestimation of harms) was high in all trials. The mean sample size was 88 participants (ranging from 40 to 200 participants) per trial. Seventy-five different herbal medicine products were tested. Herbal medicines tested in the randomised trials included single-herb products (Gynostemma pentaphyllum, Panax notoginseng, andPrunus armeniaca), proprietary herbal medicines commercially available, and combination formulas prescribed by practitioners. The most commonly used herbs wereCrataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum chinense,Cassia obtusifolia, Astragalus membranaceous, and Rheum palmatum. None of the trials reported death, hepatic-related morbidity, quality of life, or costs. A large number of trials reported positive effects on putative surrogate outcomes such as serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, alkaline phosphatases, ultrasound, and computed tomography scan. Twenty-seven trials reported adverse effects and found no significant difference between herbal medicines versus control. However, the risk of bias of the included trials was high. The outcomes were ultrasound findings in 22 trials, liver computed tomography findings in eight trials, aspartate aminotransferase levels in 64 trials, alanine aminotransferase activity in 77 trials, and glutamyltransferase activities in 44 trials. Six herbal medicines showed statistically significant beneficial effects on ultrasound, four on liver computed tomography, 42 on aspartate aminotransferase activity, 49 on alanine aminotransferase activity, three on alkaline phosphatases activity, and 32 on glutamyltransferase activity compared with control interventions. Some herbal medicines seemed to have positive effects on aspartate aminotransferase, alanine aminotransferase, ultrasound, and computed tomography. We found no significant difference on adverse effects between herbal medicine and control groups. The findings are not conclusive due to the high risk of bias of the included trials and the limited number of trials testing individual herbal medicines. Accordingly, there is also high risk of random errors.

Plain-language summary: We included 77 randomised clinical trials in this review, which tested 75 herbal medicines. All trials had high risk of systematic errors (ie, bias or risk of overestimation of benefits and overestimation of harms) as well as high risks of random errors (ie, play of chance) due to the small number of people in the trials. Herbal medicines tested in the randomised clinical trials included single-herb products (Gynostemma pentaphyllum,Panax notoginseng, andPrunus armeniaca), commercially available branded herbal medicines, and combination formulas prescribed by practitioners. Herbs most commonly included as an ingredient in different products wereCrataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum chinense,Cassia obtusifolia,Astragalus membranaceous, andRheum palmatum. We could not combine the results of the trials due to the range of different herbs used. We could not reach any conclusions about the use of herbal medicines for people with fatty liver disease as none of the trials reported results on death, liver-related illnesses, quality of life, or costs. A number of trials showed positive effects of herbal medicines compared with control interventions on enzyme activity (enzymes are proteins that cause chemical reactions in the body; eg, serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, alkaline phosphatases), ultrasound scan findings, and computed tomography scan findings. No serious adverse effects were reported for herbal medicines. However, the methodology of the trials had high risk of systematic errors (bias). Furthermore, the individual herbs were seldomly retested, and all trials had relatively low numbers of people, which increases the risk of random errors (play of chance). Therefore, the findings are inconclusive, and rigorously conducted randomised clinical trials are required to establish the benefits and harms of herbal medicines for fatty liver disease.