Metabolic Dysfunction Associated Steatotic Liver Disease

MASLD is hepatic steatosis (5% or more of hepatocytes) in a person with at least one cardiometabolic risk factor, with no other cause of fat accumulation. It replaces the term NAFLD and is the commonest chronic liver disease worldwide.

• Global prevalence is about 30%, and 70% or more in type 2 diabetes.
• Drivers are insulin resistance, adipose tissue dysfunction, de novo lipogenesis, gut dysbiosis and genetics (PNPLA3 I148M, TM6SF2).
• Fibrosis stage is the main predictor of liver related events and mortality, and cardiovascular disease is the commonest cause of death.
• A subset progresses to steatohepatitis, cirrhosis and hepatocellular carcinoma (which can arise without cirrhosis).
• Alcohol intake above 140 g weekly in women or 210 g in men moves the diagnosis to MetALD.

• Most patients are asymptomatic. Fatigue and right upper quadrant discomfort are non specific.
• Obesity, central adiposity, acanthosis nigricans, hepatomegaly.
• Cirrhosis features appear late: spider naevi, ascites, splenomegaly, encephalopathy.
• Comorbid sleep apnoea, polycystic ovary syndrome, hypothyroidism and hypertension are common.

• Ultrasound shows a bright liver, but sensitivity falls below 20% steatosis.
• Exclude other causes: alcohol, viral hepatitis, autoimmune liver disease, haemochromatosis, Wilson disease, drugs (amiodarone, methotrexate, tamoxifen, steroids).
• Stratify fibrosis with FIB-4 (below 1.3 low risk, above 2.67 high risk; use 2.0 as the lower cut-off after age 65).
• Intermediate or high FIB-4: transient elastography (below 8 kPa low risk, 8 to 12 intermediate, above 12 high risk) or enhanced liver fibrosis test.
• Biopsy for diagnostic doubt or discordant noninvasive tests.
• Screen for diabetes, dyslipidaemia, hypertension and cardiovascular risk.

• Weight loss of 7 to 10% improves steatohepatitis, and 10% or more can regress fibrosis. Use a Mediterranean diet, 150 to 300 minutes weekly of exercise, coffee, and no alcohol in advanced fibrosis.
• Resmetirom 80 mg daily (under 100 kg) or 100 mg daily (100 kg or more) for noncirrhotic F2 to F3 disease.
• Semaglutide 2.4 mg SC weekly or tirzepatide for obesity with MASH.
• Pioglitazone 30 to 45 mg daily and vitamin E 800 IU daily (nondiabetic, biopsy proven MASH only).
• SGLT2 inhibitors and GLP 1 agonists for diabetes. Statins are safe and indicated.
• Bariatric surgery for BMI 35 or more.
• Cirrhosis: ultrasound with or without AFP every 6 months, variceal screening, vaccination.
• Transplantation for decompensation or HCC.