Efficacy and safety of Qushi Huayu, a traditional Chinese medicine, in patients with nonalcoholic fatty liver disease in a randomized controlled trial

The effective treatment of non-alcoholic fatty liver disease (NAFLD) is an unmet medical need. Qushi Huayu (QSHY) is an empirical herbal formula with promising effects in NAFLD rodent models and a connection to gut microbiota regulation. This study aimed to evaluate the effects of QSHY in patients with NAFLD through a multicenter, randomized, double-blind, double-dummy clinical trial. A total of 246 eligible patients with NAFLD and liver dysfunction were evenly divided to receive either QSHY and Dangfei Liganning capsule (DFLG) simulant or QSHY simulant and DFLG (an approved proprietary Chinese medicine for NAFLD in China) for 24 weeks. The primary outcomes were changes in liver fat content, assessed using vibration-controlled transient elastography, and serum alanine aminotransferase (ALT) levels from baseline to Week 24. Both QSHY and DFLG led to reductions in liver fat content and liver enzyme levels post-intervention (p< 0.05). Compared to DFLG, QSHY treatment improved ALT (β, -0.128 [95% CI, -0.25, -0.005], p= 0.041), aspartate transaminase (β, -0.134 [95% CI, -0.256 to -0.012], p= 0.032), and fibrosis-4 score (β, -0.129 [95% CI, -0.254 to -0.003], p= 0.044) levels. QSHY markedly improved gut dysbiosis compared to DFLG, with changes in Escherichia-Shigella and Bacteroides abundance linked to its therapeutic effect on reducing ALT. Patients with a high ALT response after QSHY treatment showed superior reductions in peripheral levels of phenylalanine and tyrosine, along with an elevation in the related microbial metabolite p-Hydroxyphenylacetic acid. Our results demonstrate favorable clinical potential for QSHY in the treatment of NAFLD.