Comparative Efficacy of Herbal Products for Improving Liver Enzymes and Inflammation in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) affect adults worldwide and are causes of morbidity. While lifestyle modification remains in first-line therapy, interest has emerged in herbal agents with potential hepatometabolic effects. Evidence synthesis has been limited by heterogeneity in formulations and study quality. We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of herbal therapies in MASLD/MASH. METHODS: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and International Prospective Register of Systematic Reviews registration (CRD420251157401), PubMed, Web of Science, EMBASE, and Cochrane were searched through September 2025 for randomized controlled trials evaluating herbal therapies or derivatives in adults with MASLD/MASH. The primary outcomes included alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and liver stiffness. Random-effects NMAs estimated mean differences (MDs) with 95% confidence intervals, with treatment ranking using surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed using RoB 2.0, and certainty of evidence using Confidence in NMA. RESULTS: Across 131 randomized trials (n = 9191), several herbal interventions significantly improved liver enzymes. In the NMA for alanine aminotransferase, the greatest reductions were seen with artichoke leaf (MD -28.32; P < .01), cinnamon (MD -25.10; P = .01), and piperine (MD -25.39; P = .01), with artichoke leaf achieving the highest SUCRA (0.93). For aspartate aminotransferase, significant reductions were observed for cinnamon (MD -23.50; P < .01), berberine (MD -19.63; P < .01), and bergamot + CyC (MD -17.83; P < .01), with cinnamon being the most effective (SUCRA 0.96). For gamma-glutamyl transpeptidase, significant reductions were observed with cinnamon (MD -12.44; P = .01), garlic + silymarin (MD -10.92; P = .01), and berberine (MD -9.74; P = .01). For liver stiffness, only curcumin (MD -0.76; P = .03) and pomegranate (MD -0.86; P = .04) were statistically significant, despite higher SUCRA rankings favoring silymarin (0.81) and hesperidin + flaxseed (0.79). The secondary outcomes showed variable effects on steatosis and fibrosis indices without consistent metabolic significance. CONCLUSION: This analysis found that several herbal preparations may improve biochemical markers in MASLD and MASH, though results varied and require cautious interpretation given formulation and regulatory inconsistencies. Future work should focus on the most consistently performing agents: cinnamon, curcumin, silymarin, berberine, artichoke leaf, and Nigella sativa. This should involve standardized production, dose-finding studies, purity verification, and mainly long-term safety evaluation before any clinical integration.