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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

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 hyalin

    • Histologic features are indistinguishable from alcoholic hepatitis

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 or stavudine, 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

Diagnosis

Laboratory Tests

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

    • However, laboratory values may be normal in up to 80% of persons with hepatic steatosis

  • In contrast to alcoholic liver disease,

    • Ratio of serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) is almost always > 1 in NAFLD

    • However, it decreases to < 1 as advanced fibrosis and cirrhosis develop

  • Elevated serum ferritin levels

    • May signify so-called dysmetabolic iron overload syndrome and mildly increased body iron stores

    • May play ...

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