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Patients are often asymptomatic but sometimes complain of vague right upper quadrant discomfort. It is common to identify patients by finding hepatomegaly on exam or asymptomatic transaminase elevations.


  1. The definition of NAFLD is evidence of excessive fat in the liver, either by imaging or biopsy, in the absence of causes of secondary hepatic fat accumulation.

  2. Secondary causes of excessive fat in the liver include

    1. Significant alcohol use (> 14 drinks/week for women, > 21 for men)

    2. Wilson disease

    3. Jejunoileal bypass

    4. Prolonged total parenteral nutrition

    5. Protein-calorie malnutrition

    6. Medications

      1. Methotrexate

      2. Amiodarone

      3. Estrogens

      4. Corticosteroids

      5. Aspirin

      6. Cocaine

      7. Antiretroviral agents

  3. Patients with NAFLD have steatosis, either with or without inflammation.

    1. In simple steatosis (nonalcoholic fatty liver [NAFL]), there is no liver injury and the risk of progression to cirrhosis is < 4%.

    2. Steatosis plus inflammation, with or without fibrosis, is called nonalcoholic steatohepatitis (NASH), which is a histologic diagnosis.

      1. Up to 21% of patients with NASH and fibrosis have regression of fibrosis.

      2. Up to 40% progress to more advanced fibrosis or cirrhosis

      3. The strongest predictor of progression is the degree of inflammation on the first biopsy.

      4. Annual risk of hepatocellular carcinoma 1–2%

    3. Decompensated cirrhosis develops over 10 years in 45% of patients.

    4. The risk of hepatocellular carcinoma in patients with NAFLD cirrhosis is less than that of patients with hepatitis C cirrhosis.

  4. NAFLD can coexist with other chronic liver diseases.

  5. Epidemiology

    1. Risk factors include

      1. The metabolic syndrome

      2. Obesity

      3. Type 2 diabetes mellitus

      4. Insulin resistance

      5. Hyperlipidemia

      6. Family history of NAFLD

    2. Prevalence varies based on population studied.

      1. Worldwide prevalence is approximately 25%, higher in the Middle East and South Asia; NASH prevalence 3–5%

      2. In patients with NAFLD in North America, 80% are obese, 25% have diabetes, and 83% have hyperlipidemia.

      3. Found in > 95% patients undergoing bariatric surgery and 50% of patients attending lipid clinics

      4. Second most common reason for liver transplant and will likely overtake hepatitis C in the near future

    3. Most common cause of abnormal liver test results in the United States.


  1. Blood tests

    1. Transaminase elevation is usually < 400 units/L, with ALT > AST; in advanced fibrosis or cirrhosis, AST may be > ALT.

    2. Serum ferritin is elevated in 60% of patients but is rarely > 1000 mcg/L.

    3. Alkaline phosphatase is elevated in 30% of patients.

  2. Imaging can detect steatosis when it replaces more than 30% of the liver volume; it cannot distinguish NAFL from NASH.

    1. Ultrasonography

      1. Sensitivity, 82–100%; specificity, ∼95% %

      2. LR+, 18.2; LR–, 0.09

    2. CT scan

      1. Similar sensitivity and specificity to ultrasonography

      2. However, more expensive and patient is exposed to radiation

    3. MRI

      1. Sensitivity, ∼95%; specificity, ∼95%

      2. LR+, 19; LR–, 0.05

      3. Higher sensitivity and specificity for detecting steatosis > 5% of the liver compared to ultrasonography and CT

  3. Liver biopsy is the gold standard for diagnosis and staging.

    1. NASH is missed in 27% of single biopsies.

    2. Test characteristics of a single biopsy for the diagnosis of NASH

      1. Sensitivity, 73%; specificity, ...

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