The dynamic spectrum of steatotic liver disease: the global perspective

Abstract

Steatotic liver disease (SLD) comprises metabolic dysfunction-associated SLD, metabolic and alcohol-related liver disease, and alcohol-related liver disease, conditions that frequently overlap rather than fall into distinct categories. Cardiometabolic risk factors (CMRFs), including obesity, type 2 diabetes, hypertension and dyslipidaemia, are highly prevalent across SLD subtypes, with most patients exhibiting multiple metabolic abnormalities. These risks interact synergistically with alcohol exposure, accelerating fibrosis progression to cirrhosis and liver mortality. Importantly, both alcohol consumption and metabolic risks are dynamic and can fluctuate over time, leading to transitions across the SLD spectrum that static diagnostic thresholds might not adequately capture. Misclassification is common, particularly due to under-reporting of alcohol intake, underscoring the value of objective alcohol biomarkers such as phosphatidylethanol. Accurate risk stratification, therefore, requires an integrated approach combining systematic alcohol screening, structured evaluation of CMRFs and non-invasive fibrosis assessment. Management must be multidisciplinary, combining alcohol reduction strategies, optimization of metabolic control and liver-directed therapies. However, most emerging pharmacotherapies for metabolic dysfunction-associated steatohepatitis exclude individuals with concurrent alcohol use, creating a gap between clinical trial populations and real-world practice. A dynamic, spectrum-based framework incorporating repeated reassessment of alcohol and metabolic risks offers the most pragmatic path for diagnosis, treatment and equitable care delivery in SLD.