From steatosis to cirrhosis: the role of obesity in the progression of liver disease

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common subtype of steatotic liver disease (SLD), affects approximately 38% of the global adult population and is strongly linked to obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). Projections estimate its prevalence may exceed 55% by 2040. Obesity plays a central role in the progression from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Excess adiposity contributes to hepatic fat accumulation, systemic inflammation, insulin resistance, and activation of hepatic stellate cells. key mechanisms in liver injury and fibrogenesis. Diagnosis traditionally relied on liver biopsy, but noninvasive techniques, along with serum-based indices, are now commonly used. MASLD is associated with an increased risk of cardiovascular disease, chronic kidney disease, and endocrine disorders, particularly in obese individuals. Management is centered on weight reduction, which can reverse steatosis, resolve MASH, and regress fibrosis depending on the degree of weight loss. Recent therapeutic advances include the approval of resmetirom, a thyroid hormone receptor-β agonist, and promising results from glucagon-like peptide 1 (GLP-1) receptor agonists. Bariatric surgery offers significant benefits in selected patients, improving liver histology and associated metabolic parameters. Despite these developments, no universally accepted pharmacotherapy exists for MASLD. Future directions include expanding access to diagnostic tools, validating novel biomarkers, and implementing public health strategies targeting obesity to prevent progression to end-stage liver disease.