Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD)
MASLD (formerly NAFLD) is hepatic steatosis with at least one cardiometabolic risk factor after exclusion of significant alcohol use and other liver disease, and a subset progresses to steatohepatitis (MASH, formerly NASH) with inflammation and fibrosis. Diagnosis rests on imaging-confirmed steatosis plus noninvasive fibrosis risk stratification, and management centers on 7% to 10% weight loss with aggressive treatment of diabetes and dyslipidemia.
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What this article covers
- Overview
Definition: MASLD is hepatic steatosis, fat in at least 5% of hepatocytes, together with at least one cardiometabolic risk factor (obesity, type 2 diabetes or prediabetes, hypertension…
- Epidemiology
Most common cause of chronic liver disease: roughly 30% of the U.S.
- Risk factors
Central obesity: the strongest and most consistent risk factor, correlating with the degree of hepatic fat accumulation.
- Pathophysiology
Insulin resistance drives hepatic fat accumulation: increased free fatty acid delivery and hepatic de novo lipogenesis exceed the capacity for fatty-acid oxidation and export, so triglyceride accumulates in hepatocytes as steatosis.
- Clinical features
Usually asymptomatic: most patients with steatosis or early MASH have no symptoms and are identified incidentally through abnormal liver chemistries or fatty liver seen on imaging obtained for another reason.
- Differential diagnosis
Alcohol-associated liver disease: similar steatosis and steatohepatitis histology, but distinguished by a quantitative alcohol history, an AST:ALT ratio typically greater than 2, macrocytosis, and…
- Diagnosis
Establish the diagnosis by combining steatosis with a cardiometabolic risk factor after exclusion of other causes: MASLD is diagnosed when hepatic steatosis is confirmed on imaging or biopsy in a…
- Management
Start with structured weight loss as first-line therapy for all patients: diet and lifestyle modification targeting 7% to 10% total body weight loss, since a loss of at least 5% improves steatosis…
- Complications
Progressive fibrosis and cirrhosis: the central complication of unrecognized or untreated MASH, occurring in roughly 10% of patients with steatosis over time.
- Prognosis
Fibrosis stage, not steatosis grade, predicts outcome: the amount of fat on imaging does not predict prognosis, whereas the stage of fibrosis on biopsy is the strongest predictor of liver-related morbidity and mortality.
- Prevention
Screen patients with type 2 diabetes or prediabetes and any hepatic risk marker: obtain liver chemistries or hepatic ultrasonography, and evaluate further for MASH and fibrosis if ALT is elevated or steatosis is seen.
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- Hepatocellular carcinoma
Hepatocellular carcinoma is a primary liver cancer that arises almost exclusively in cirrhosis and can be diagnosed non-invasively when multiphase CT or MRI shows arterial-phase hyperenhancement with portal-venous washout in a lesion at least 1 cm. Treatment is stratified by tumor burden, liver function, and vascular or extrahepatic spread, ranging from resection or ablation through transplantation and transarterial chemoembolization to systemic atezolizumab-bevacizumab for advanced disease.
- Dyslipidemia
Dyslipidemia is an abnormal lipid profile, chiefly elevated LDL cholesterol, that drives atherosclerotic cardiovascular disease. Management is risk-based LDL lowering with statins as the foundation, adding ezetimibe and PCSK9 inhibitors to reach targets, alongside lifestyle change and evaluation for severe genetic forms and hypertriglyceridemia.
- Type 2 diabetes mellitus
Type 2 diabetes is hyperglycemia from insulin resistance with progressive relative insulin deficiency, diagnosed by a hemoglobin A1c of 6.5% or higher, a fasting glucose of 126 mg/dL or higher, or a 2-hour oral glucose tolerance test value of 200 mg/dL or higher. First-line treatment is lifestyle modification plus metformin, with an SGLT2 inhibitor or GLP-1 receptor agonist added early for patients with atherosclerotic disease, kidney disease, or heart failure.
- Obesity
Obesity is a chronic disease of excess adiposity, defined by a body mass index of 30 or greater, that raises risk for type 2 diabetes, cardiovascular disease, sleep apnea, liver disease, and several cancers. Management is staged: lifestyle intervention for all patients, pharmacotherapy after 3 to 6 months of unmet lifestyle goals, and bariatric surgery for a body mass index of 40 or greater or 35 or greater with a comorbidity.
- Evaluation of abnormal liver function tests (LFTs)
Abnormal liver chemistries are evaluated by first classifying the pattern as hepatocellular (AST/ALT predominant), cholestatic (ALP/bilirubin predominant), or isolated hyperbilirubinemia, then pursuing an ordered, pattern-specific workup for viral, autoimmune, metabolic, toxic, infiltrative, and obstructive causes.