Metabolic Dysfunction-Associated Steatotic Liver Disease (MΑSLD)

Metabolic dysfunction-associated steatotic liver disease (MΑSLD) is a broad term used to cover a spectrum of conditions characterized by evidence of hepatic steatosis on imaging or histology. MASLD is a broad term used to encompass a spectrum of conditions characterized by evidence of hepatic steatosis on imaging or histology in patients with at least 1 metabolic risk factor (eg, obesity, diabetes mellitus, dyslipidemia, hypertension). MASLD represents a significant evolution in the terminology and conceptual framework surrounding hepatic steatosis. Historically, liver fat accumulation without significant alcohol intake was categorised under nonalcoholic fatty liver disease (NAFLD). However, recent shifts in nomenclature arose primarily to address 2 core issues. Firstly, the term "fatty" was replaced with "steatotic" to mitigate the stigma associated with the former term. Secondly, defining a disease by exclusion, eg, "nonalcoholic," was widely criticised for its inherent ambiguity and lack of specificity, akin to labelling conditions like myocardial infarction as "non-cocaine myocardial infarction," which is considered conceptually inadequate. The pivotal shift in terminology was initiated by the landmark paper from Eslam et al, introducing the term Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), thereby directly associating hepatic steatosis with underlying metabolic dysfunction rather than excluding alcohol consumption alone. This redefinition marked a significant departure from NAFLD, emphasizing pathophysiological mechanisms linked to components of metabolic syndrome. Subsequently, following broader international consensus, MAFLD was refined further to MASLD, establishing clearer diagnostic criteria and positioning it within a broader spectrum of conditions collectively termed Steatotic Liver Disease (SLD). This evolution reflects a more precise and mechanistically informed approach to understanding hepatic steatosis, enhancing clinical and research clarity. Steatotic liver disease is categorized into the following types: : MASLD is defined by ≥5% hepatic steatosis and the presence of at least 1 cardiometabolic risk factor (eg, dyslipidemia or obesity), with no other underlying causes and minimal or no alcohol intake (ie, <20 g/day for females and <30 g/day for males). Formerly known as NAFLD, MASLD is the hepatic manifestation of metabolic syndrome. : MASH, previously called nonalcoholic steatohepatitis (NASH), is a progressive form of MASLD marked by liver inflammation and hepatocellular injury, with or without fibrosis. : MetALD refers to patients with hepatic steatosis, at least 1 metabolic risk factor, and moderate alcohol consumption, defined as 20 to 50 g/day for females and 30 to 60 g/day for males. This condition may result from a combination of metabolic dysfunction and moderate alcohol consumption, representing a spectrum between MASLD-predominant and alcohol-predominant disease. : Patients with steatosis and heavy alcohol use (>50 g/day for females, >60 g/day for males), with a standard drink containing approximately 14 g of alcohol, are classified with alcohol-associated liver disease (ALD). Although MASLD can coexist with other causes of steatosis, eg, celiac disease, medications, or genetic conditions, this discussion focuses on MASLD in the absence of those factors. A diagnostic approach for steatotic liver diseases (SLD) other than MASLD, MetALD, and ALD has been established, highlighting critical clinical features and recommended investigations (see . Steatotic Liver Disease Diagnosis). Understanding the etiology and pathophysiology of MASLD and its subtypes is critical for clinicians, emphasizing the need for interprofessional collaboration in diagnosis and management. The cardiometabolic risk factors defining metabolic dysfunction include: :  A BMI of ≥25 kg/m² in the general population or  ≥23 kg/m² in individuals of Asian ancestry.  (waist circumference thresholds): • Waist circumference of  ≥94 cm in men and  ≥80 cm in women of European ancestry • Waist circumference of  ≥90 cm in men and  ≥80 cm in women of South-Asian or Chinese ancestry • Waist circumference of  ≥85 cm in men and  ≥90 cm in women of Japanese ancestry.  Glycated haemoglobin (HbA1c) 5.7% to 6.4 %; fasting plasma glucose ranging from 100 to 125 mg/dL. HbA1c of  ≥6.5%; fasting plasma glucose of  ≥126 mg/dL.  Plasma triglycerides ≥150 mg/dL or treatment with lipid-lowering agents.  <40 mg/dL in men or ≤50 mg/dL in women. : Resting blood pressure of 130/85 mm Hg or greater or ongoing antihypertensive treatment.