Global epidemiology of metabolic and alcohol-associated liver disease: risk factors, natural history and clinical implications.

Metabolic and alcohol-associated liver disease (MetALD) is driven by alcohol consumption and the presence of cardiometabolic risk factors (CMRFs), mainly obesity and diabetes. Since its formal definition in 2023, accumulating evidence suggests that MetALD affects approximately 4.1% of the global adult population, with marked regional heterogeneity. However, under-recognition remains pervasive because alcohol intake is systematically under-reported; objective biomarkers such as phosphatidylethanol increase the diagnosis of MetALD by up to fourfold. Moreover, MetALD confers a substantially higher risk of progression to cirrhosis, hepatocellular carcinoma and major adverse liver outcomes compared with metabolic dysfunction-associated steatotic liver disease. Emerging data indicate that alcohol and CMRFs act synergistically rather than additively, accelerating liver inflammation and fibrosis. Cost-effectiveness analyses support risk-based screening that couples simple blood-based non-invasive tests with imaging and advanced serum biomarkers of liver fibrosis. Key research priorities include refining epidemiological estimates, standardizing biomarker cut-offs, elucidating dynamic interactions between alcohol and CMRFs, validating non-invasive prognostic tools, and evaluating therapies that target both metabolic and alcohol-related injury. Addressing these gaps is essential to mitigate the growing clinical and economic burden of MetALD.