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For further information, see CMDT Part 16-10: Nonalcoholic Fatty Liver Disease

Key Features

Essentials of Diagnosis

  • Often asymptomatic

  • Elevated serum aminotransferase levels, hepatomegaly, and/or steatosis on ultrasonography

  • Predominantly macrovesicular steatosis with or without inflammation and fibrosis on liver biopsy

General Considerations

Nonalcoholic fatty liver disease (NAFLD)

  • Causes include obesity (present in ≥ 40%), diabetes mellitus (in ≥ 20%), and hypertriglyceridemia (in ≥ 20%) in association with insulin resistance as part of the metabolic syndrome; the risk of NAFLD in persons with metabolic syndrome is 4 to 11 times higher than that of persons without insulin resistance

  • Nonobese persons (more frequently Asians) account for 3–30% of persons with NAFLD and have metabolic profiles characteristic of insulin resistance

  • Persons with NAFLD are at increased risk for cardiovascular disease, chronic kidney disease, and colorectal cancer

  • The frequency and severity of NAFLD is greater in men than in women during reproductive age, but after menopause the frequency is higher in women than men, suggesting that estrogen is protective

Nonalcoholic steatohepatitis (NASH)

  • Results from progression of macrovascular steatosis to steatohepatitis and fibrosis

  • Characterized histologically by the macrovesicular steatosis of NAFLD with

    • Focal infiltration by polymorphonuclear neutrophils

    • Mallory hyaline

    • Histologic features are indistinguishable from alcoholic hepatitis

  • Histologic severity is increased in women who take synthetic hormones (oral contraceptives and hormone replacement therapy)

Other causes of fatty liver disease

  • Cushing syndrome and hypopituitarism

  • Excessive dietary fructose consumption

  • Starvation and refeeding syndrome

  • Hypobetalipoproteinemia

  • Polycystic ovary syndrome

  • Hypothyroidism

  • Obstructive sleep apnea

  • Total parenteral nutrition

  • Psoriasis (NAFLD)

  • Soft drink consumption (NAFLD)

  • Cholecystectomy (NAFLD)

  • Medications: corticosteroids, amiodarone, diltiazem, tamoxifen, irinotecan, oxaliplatin, and antiretroviral therapy

  • Toxins: vinyl chloride, carbon tetrachloride, yellow phosphorus

Causes of microvesicular steatosis

  • Reye syndrome

  • Medications: didanosine, stavudine, linezolid, valproic acid, tetracycline

  • Acute fatty liver of pregnancy

  • Women in whom fatty liver of pregnancy develops often have a defect in fatty acid oxidation due to reduced long-chain 3-hydroxyacyl-CoA dehydrogenase activity

Clinical Findings

Symptoms and Signs

  • Most patients with NAFLD are asymptomatic or have only mild right upper quadrant discomfort

  • Hepatomegaly is present in 75% of patients with NASH, but the stigmas of chronic liver disease are uncommon

  • Signs of portal hypertension generally signify advanced liver fibrosis or cirrhosis but occasionally occur in patients with mild or no fibrosis and severe steatosis

Differential Diagnosis

  • Alcoholic fatty liver disease

  • Hepatitis, eg, viral, alcoholic, toxic

  • Cirrhosis

  • Heart failure

  • Hepatocellular carcinoma or metastatic cancer


Laboratory Tests

  • There may be mildly elevated serum aminotransferase and alkaline phosphatase levels

    • However, laboratory values may be normal in up ...

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