Nonalcoholic fatty liver disease (NAFLD)

  • Definition

    • Hepatic steatosis - Excessive fat accumulation in liver (intracellular fat in >5% hepatocytes)

    • Nonalcoholic fatty liver disease (NAFLD) – Hepatic steatosis present in the absence of other causes of steatosis (eg. alcohol)

    • Nonalcoholic steatohepatitis (NASH)- Hepatic steatosis with hepatic injury/inflammation on biopsy

  • Cirrhosis develops when simple steatosis -> steatohepatitis -> fibrosis

    • Hepatocellular carcinoma (HCC) is associated with cirrhosis due to NAFLD (2.4-12.8% over three years)

Risk factors for progression

  • Obesity

  • DM2

  • Dyslipidemia

  • Metabolic syndrome (BP, fasting glucose, HDL, TG, waist circumference)

  • ALT and AST > 2 ULN

Note: Coffee consumption associated with lower risk of progression

DDx of secondary hepatic steatosis

  • Macrovesicular steatosis

    • Alcohol consumption

    • Hepatitis C

    • Wilson’s disease

    • Lipodystrophy

    • Starvation

    • Parenteral nutrition

    • Abetalipoproteinemia

    • Medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids)

  • Microvesicular steatosis

    • Reye’s syndrome

    • Medications (valproate, anti-retroviral medicines)

    • Acute fatty liver of pregnancy

    • HELLP syndrome

    • Inborn errors of metabolism (e.g., LCAT deficiency, cholesterol ester storage disease, Wolman disease)


  • Alcohol intake

  • Medication review and history of steatosis-associated drugs

  • Person and family history of diabetes, hypertension, cardiovascular disease, cirrhosis

  • BMI, waist circumference, body weight change


  • CBC (platelets)

  • AST, ALT, Alk phos, Bilirubin

  • Albumin

  • HBsAg, Anti-HCV Ab

  • Ferritin, iron

  • Fasting glucose, A1C

  • Lipid panel

  • INR

  • Consider additional testing in patients with abnormal liver tests or family history of cirrhosis

    • ANA, anti-SM, anti-LKM

    • Other: a-1 antitrypsin, ceruloplasmin, anti-TTG/IgA, TSH


  • Ultrasound first-line

  • May consider MRI/CT


  • Exercise and Weight loss

  • Avoid alcohol consumption

  • Diet - Calorie-restricted (aim 1kg/week)

    • Consider referral to dietician

    • May consider Orlistat if fail lifestyle intervention and BMI>30, only continue if >5% weight loss in 3 months (max one year to avoid risk of Vitamin deficiency)

    • Benefit of bariatric surgery in NASH unclear

  • Hepatitis A and B vaccination if no serologic evidence of immunity

    • Pneumoccocal vaccine and age-appropriate vaccine

  • Treat comorbid conditions, such as diabetes, hyperlipidemia, hypertension, or sleep apnea

    • Statins are not contraindicated (not at increased risk of hepatotoxicity)

  • Calculate risk score

    • If FIB-4>1.30 (or Fibrosis Score ≥ F2), consider referral for fibroscan

    • If low, consider recalculate score q2-5 years

Indications for additional investigation (Biopsy vs. Fibroscan)

  • Peripheral stigmata of chronic liver disease (suggestive of cirrhosis)

  • Splenomegaly (suggestive of cirrhosis)

  • Cytopenias (suggestive of cirrhosis)

  • Serum ferritin >1.5 times the upper limit of normal (suggestive of NASH and advanced fibrosis)

  • >45 years of age with associated obesity or diabetes (increased risk of advanced fibrosis)

  • Other:

    • ALT:AST >1

    • ALT/AST elevated > 6 months

Management of Biopsy-Proven NASH

  • Medications if biopsy-proven pre-cirrhotic NASH who failed lifestyle

    • May consider Vitamin E 800 units/day in non-diabetic

      • Risk of hemorrhagic stroke, prostate cancer

    • Thiazolidinediones: Pioglitazone 30mg/day

      • Risk of weight gain, CHF, bladder CA, osteoporosis

  • NASH Cirrhosis should undergo HCC screening with serial ultrasound q6 months and endoscopy for varices screening