Metabolic dysfunction associated steatotic liver disease: mechanisms, diagnosis, and management in adults.

Abstract

Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally and a major cause of liver related and cardiometabolic morbidity. MASLD is defined by the presence of hepatic steatosis and at least one of five cardiometabolic features in the absence of secondary causes of liver disease and substantial alcohol consumption (>20 g/day for women and 30 g/day for men). The recent reclassification of non-alcoholic fatty liver disease to MASLD represents a paradigm shift towards recognising the central role of systemic metabolic dysfunction and cardiometabolic risk factors in the pathogenesis of the disease and development of complications. The pathophysiology of MASLD is complex, multifaceted, and interconnected, involving adipose tissue dysfunction, altered hepatic lipid metabolism, mitochondrial and endoplasmic reticulum stress, dysregulation of the gut-liver axis, and genetic predisposition. The severity of liver fibrosis remains the strongest predictor of all cause mortality and liver specific morbidity and mortality, and the burden of cardiometabolic dysfunction affects the risk of complications in MASLD. Non-invasive serum based and imaging based biomarkers are crucial in identifying advanced liver fibrosis and guiding risk stratification. This narrative review summarises the current understanding of the pathogenesis of MASLD, the clinical use of non-invasive diagnostics, and compares international guidelines for disease management. This review also discusses approved and emerging treatment options for MASLD, recognising the current need for developing strategies for monitoring the efficacy of treatment.