Effects and safety of Huatan Qushi Huoxue granules on obesity-associated non-alcoholic fatty liver disease: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a major global health issue strongly associated with obesity. Available treatments have significant limitations. The traditional Chinese medicine Huatan Qushi Huoxue (HTQSHX) granules represent a potential alternative therapeutic option. This study evaluates their effects and safety in patients with obesity-associated NAFLD.

METHODS

This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial recruited 248 patients with obesity-associated NAFLD from three clinical sites. Participants were randomized 1:1 to receive HTQSHX granules or placebo granules for 12 weeks. The primary outcome was the absolute change in hepatic fat fraction from baseline to week 12, as measured by MRI-proton density fat fraction (MRI-PDFF), which is recommended as a primary endpoint in early-phase NAFLD clinical trials for its precision and objectivity. Secondary outcomes included the proportion of patients achieving ≥30% relative reduction in MRI-PDFF-assessed hepatic fat fraction, serum liver enzyme indicators, glucose and lipid metabolism parameters, non-alcoholic steatohepatitis-related serum biomarkers, anthropometric measures, and serum metabolomics analysis.

RESULTS

Among 228 participants included in the modified intention-to-treat (mITT) analysis, the median hepatic fat fraction decreased from 16.15% at baseline to 12.12% in the HTQSHX group (median change: 3.27%), and from 15.64% to 14.95% in the placebo group (median change: 0.96%). The between-group difference in absolute change was statistically significant (-2.32%; 95% CI, -4.50 to -0.23; P = 0.029). The proportion of patients achieving a ≥30% relative reduction in hepatic fat fraction was significantly higher in the HTQSHX group than in the placebo group (41.23% vs. 20.18%; P < 0.001). The HTQSHX group also showed significantly greater improvements in serum alanine aminotransferase (P = 0.048), aspartate aminotransferase (P = 0.033), free fatty acids (P = 0.026), cytokeratin-18 fragment M30 (P < 0.001), soluble triggering receptor expressed on myeloid cells 2 (P < 0.001) and anthropometric parameters (body mass index, waist-to-hip ratio, body fat percentage). Metabolomics analysis of 30 HTQSHX-treated participants revealed that the formula restored multiple phospholipid levels and reduced markers of oxidative stress and mitochondrial dysfunction, with enrichment in fatty acid and sphingolipid metabolism pathways.

CONCLUSION

HTQSHX granules may represent a potentially beneficial therapeutic option for obesity-associated NAFLD, with observed effects including significant reduction in hepatic fat fraction and modulation of lipid metabolism and oxidative stress, alongside an acceptable safety profile. These findings warrant further investigation in longer-term studies.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2200060901.