EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Fig. 1.

Flow-chart for SLD and its sub-categories [2]. SLD, diagnosed histologically or by imaging, has many potential aetiologies. MASLD is defined as the presence of hepatic steatosis in conjunction with (at least) one cardiometabolic risk factor and no other discernible cause. The quantity of alcohol intake, the drinking pattern, and the type of alcohol consumed should be assessed in all individuals with SLD using detailed medical history, psychometric instruments and/or validated biomarkers. ALD, alcohol-related liver disease; DILI, drug-induced liver disease; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, MASLD with moderate (increased) alcohol consumption; SLD, steatotic liver disease.

Fig. 2.

Proposed strategy for non-invasive assessment of the risk for advanced fibrosis and liver-related outcomes in individuals with metabolic risk factors or signs of SLD. Individuals with (A) T2D or (B) abdominal obesity and ≥1 additional cardiometabolic risk factor(s) or (C) persistently elevated liver enzymes should undergo a multi-step diagnostic process, as indicated in the figure, to identify individuals with MASLD and advanced fibrosis. The algorithm can also be applied in case of incident finding of steatosis. This strategy is intended to identify individuals at risk of developing liver-related outcomes. ELF, enhanced liver fibrosis; FIB-4, fibrosis-4 index; GLP1RA, glucagon-like peptide-1 receptor agonist; MRE, magnetic resonance elastography; SLD, steatotic liver disease; SWE, shear wave elastography; VCTE, vibration-controlled transient elastography.

Fig. 3.

Lifestyle management algorithm for MASLD. Note: Behavioural therapy includes: self-monitoring, clinicians providing affected individuals with self-efficacy and motivation, setting realistic negotiable goals, and overcoming barriers. Examples of unprocessed/minimally processed foods: vegetables, fruits (not juice), low-fat dairy, nuts, olive oil, legumes, unprocessed fish and poultry. Overweight/obesity: Overweight: BMI of 25–29.9 kg/m² (non-Asian) or 23–24.9 (Asian), Obesity: ≥30 kg/m² (non-Asian) ≥25 kg/m² (Asian). Class II obesity: BMI ≥35 kg/m² (non-Asian) or BMI ≥30 kg/m² (Asian). Normal weight: BMI<25 kg/m² (non-Asian) or <23 kg/m² (Asian). BMI, body-mass index; HCC, hepatocellular carcinoma; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; T2D, type 2 diabetes.

Fig. 4.

Treatment recommendations beyond lifestyle modification in MASLD/MASH. The recommended choice of pharmacological treatment options in individuals with MASLD/MASH is dependent on comorbidities and stage of disease. BMI, body mass index; GLP1RA, glucagon-like peptide 1 receptor agonist; HCC, hepatocellular carcinoma; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; SGLT2, sodium-glucose cotransporter 2; T2D, type 2 diabetes.

Fig. 5.

Cardiovascular work-up algorithm in the evaluation of individuals with MASLD before liver transplantation. Adults with MASLD who are candidates for liver transplantation should be evaluated by a multidisciplinary team using a stepwise and risk-adjusted cardiac work-up algorithm to mitigate the risk of major cardiovascular events in the pre-, peri- and post-transplant phase (modified from [496, 497]). CCTA, coronary computed tomography angiography; CV, cardiovascular; DSE, dobutamine stress echocardiography; ECG, electrocardiogram; LT, liver transplantation; TTE, transthoracic echocardiography. *Indicates suboptimal sensitivity in high-risk populations.