Steatotic Liver Disease

Steatotic Liver Disease

Steatotic liver disease (SLD), and specifically its metabolic subtype metabolic dysfunction-associated steatotic liver disease (MASLD), represents a reclassification of what was previously known as non-alcoholic fatty liver disease (NAFLD). The updated nomenclature, adopted by major hepatology societies in 2023, was introduced to more accurately reflect the metabolic etiology of the condition and to remove the potentially stigmatizing “non-alcoholic” qualifier. MASLD is defined by the presence of hepatic steatosis — fat accumulation in >5% of hepatocytes — in conjunction with at least one cardiometabolic risk factor such as obesity, type 2 diabetes, dyslipidemia, or hypertension.

MASLD encompasses a broad disease spectrum ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The global prevalence of MASLD is estimated at approximately 30% of the adult population, making it the most common chronic liver disease worldwide. The condition is driven primarily by insulin resistance, which promotes hepatic de novo lipogenesis and impairs the export of triglycerides from the liver. Diagnosis relies on imaging modalities such as ultrasound, controlled attenuation parameter measurement, or MRI-derived proton density fat fraction, with liver biopsy reserved for staging in selected cases.

Clinical Relevance to Retatrutide

Retatrutide has demonstrated compelling effects on hepatic fat content that are directly relevant to the management of MASLD. In phase 2 trials, treatment with retatrutide at doses of 8 mg and 12 mg resulted in mean relative reductions in liver fat exceeding 80%, with a substantial proportion of participants achieving normalization of liver fat content. The glucagon receptor component of retatrutide is thought to play a central role in these hepatic benefits by stimulating fatty acid oxidation within hepatocytes and reducing de novo lipogenesis. These data have generated significant interest in retatrutide as a potential therapeutic option for MASLD and its progressive form MASH, conditions for which approved pharmacological treatments remain limited.