Metabolic-Associated Fatty Liver Disease

Metabolic associated fatty liver disease is hepatic steatosis (over 5 percent of hepatocytes) in a person with overweight or obesity, type 2 diabetes, or evidence of metabolic dysregulation.

• It is the most common chronic liver disease; global prevalence about 25 to 30 percent, rising with urbanisation in Africa.
• Spectrum: simple steatosis, steatohepatitis (inflammation and ballooning with or without fibrosis), fibrosis, cirrhosis and hepatocellular carcinoma (which can develop without cirrhosis).
• Risk factors: central obesity, type 2 diabetes, dyslipidaemia, hypertension, insulin resistance, polycystic ovary syndrome, obstructive sleep apnoea, sedentary lifestyle, high fructose intake, genetic variants (PNPLA3), HIV on antiretroviral therapy.

Usually asymptomatic; incidental raised ALT or fatty liver on ultrasound.

• Fatigue, right upper quadrant discomfort, hepatomegaly, acanthosis nigricans.
• Cirrhosis: spider naevi, splenomegaly, ascites, jaundice.
• Differential diagnosis: alcohol-related liver disease, viral hepatitis, drug-induced steatosis (amiodarone, tamoxifen, methotrexate, corticosteroids, valproate), haemochromatosis, Wilson disease, coeliac disease, hypothyroidism, lipodystrophy, autoimmune hepatitis.
• Complications: cirrhosis (10 to 20 percent of steatohepatitis over 10 to 20 years), hepatocellular carcinoma, cardiovascular disease (leading cause of death), chronic kidney disease, type 2 diabetes, colorectal cancer.

Ultrasound shows bright echotexture; CT or MRI proton density fat fraction quantifies fat.

• Exclude other causes: alcohol history (below 20 g daily in women, below 30 g in men), hepatitis B and C serology, iron profile, autoimmune markers, ceruloplasmin, coeliac serology, thyroid function.
• Fibrosis staging: a non-invasive score from age, AST, ALT and platelets; transient elastography (stiffness below 8 kPa makes advanced fibrosis unlikely; above 12 kPa suggests cirrhosis); liver biopsy if uncertain.
• Metabolic work-up: fasting glucose or HbA1c, lipids, blood pressure, waist circumference, urate.

Supportive

• Weight loss of 7 to 10 percent of body weight (improves steatosis and inflammation; 10 percent or more regresses fibrosis); Mediterranean style diet, avoid sugar sweetened drinks and fructose; aerobic and resistance exercise at least 150 minutes weekly; stop smoking; limit alcohol.

Pharmacological

• Treat comorbidities: statins are safe and encouraged (atorvastatin 20 to 40 mg at night); control blood pressure and glycaemia.
• Type 2 diabetes with steatohepatitis: pioglitazone 30 to 45 mg daily (watch weight gain, fluid and fractures); semaglutide 1 mg weekly (up to 2.4 mg weekly for obesity) or liraglutide 1.8 mg daily; SGLT2 inhibitors (empagliflozin 10 mg daily) improve steatosis and cardiovascular outcomes.
• Biopsy proven steatohepatitis with fibrosis (stage 2 or 3): resmetirom 80 mg once daily (100 mg if weight 100 kg or more) where available; vitamin E 800 IU daily in non-diabetic, non-cirrhotic patients (prostate cancer and haemorrhagic stroke concerns).
• Metformin has no histological benefit but is used for diabetes.

Procedures: bariatric surgery for obesity with body mass index 35 kg/m2 or above (30 with diabetes), reducing steatohepatitis and fibrosis; endoscopic screening for varices in cirrhosis; liver transplantation for decompensated disease.

Surveillance: ultrasound with or without alpha-fetoprotein every 6 months in cirrhosis; fibrosis reassessment every 1 to 3 years by risk.

Special groups: children (lifestyle first), pregnancy (lifestyle; stop pioglitazone and vitamin E), HIV (change antiretroviral drugs causing weight gain or dyslipidaemia where possible).

Red flags: ALT above 3 times the upper limit with fibrosis, falling platelets, jaundice, ascites, rising alpha-fetoprotein.

Follow-up: liver profile, weight and metabolic review every 3 to 6 months; cardiovascular risk management; vaccination against hepatitis A and B.