Nutrients as epigenetic modulators in metabolic dysfunction-associated steatotic liver disease

Table 1 Summary of key clinical trials and meta-analyses evaluating therapeutic interventions in metabolic dysfunction-associated steatotic liver disease

Study	Intervention	Population	Key findings	Ref.
PIVENS trial	Vitamin E, pioglitazone vs placebo	Non-diabetic MASLD patients	Vitamin E improved liver histology	Chalasani et al[107], 2009
TONIC study	Vitamin E and metformin	Pediatric MASLD patients	Improved hepatocellular ballooning and MASLD activity score; no improvement in ALT levels	Lavine et al[99], 2011
FLINT trial	Obeticholic acid	MASLD patients	Reduced fibrosis progression	Gao et al[91], 2011
European meta-analysis	Dietary and lifestyle modifications	MASLD and MASH patients	Significant risk reduction with dietary intervention	Buzzetti et al[77], 2021
Lancet meta-analysis	Lifestyle, pharmacological Interventions	MASLD patients (meta-analysis of 15 RCTs)	Validated efficacy of lifestyle and pharmacological interventions	Mózes et al[108], 2023
MAESTRO-NASH trial	Resmetirom (thyroid hormone receptor-β agonist)	MASLD with liver fibrosis (phase 3 RCT)	Promising reduction of hepatic fat and fibrosis	Harrison et al[109], 2024
-	MUFA vs SFA intake	MASLD patients with genetic stratification	MUFA may contribute to disease progression	Xu et al[75], 2024
Semaglutide trial (NEJM)	Semaglutide (GLP-1 receptor agonist)	MASH patients with compensated cirrhosis (phase 3 RCT)	Significant improvements in steatohepatitis and fibrosis	Sanyal et al[110], 2025

This table provides an overview of pivotal clinical trials and meta-analyses assessing pharmacological and non-pharmacological interventions in metabolic associated steatotic liver disease. It summarizes study design, target population, main outcomes, and references, organized chronologically to reflect the progression of evidence from 2009 to 2025. MASLD: Metabolic dysfunction-associated steatotic liver disease; MASH: Metabolic dysfunction-associated steatohepatitis; RCT: Randomized clinical trial; MUFA: Monounsaturated fatty acid; SFA: Saturated fatty acid.