Fatty Liver Disease, Nonalcoholic

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)

• Most common causes include obesity (present in ≥ 40%), diabetes mellitus (in ≥ 20%), 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

• In fact, the alternative designation "metabolic-associated (or metabolic dysfunction‒associated) fatty liver disease" (MAFLD) has been proposed

• Nonobese persons (more frequently Asians) account for 10–20% of persons with NAFLD and have metabolic profiles characteristic of insulin resistance

• Less common causes include psoriasis, cholecystectomy, and excessive dietary fructose (eg, soft drink) consumption

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

• Maternal obesity and higher maternal early-pregnancy glucose concentrations in mothers of European ancestry are associated with NAFLD in offspring

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

• Affects 3–6% of the US population and leads to cirrhosis in approximately 20% of affected persons

Other causes of fatty liver disease

• Cushing syndrome and hypopituitarism

• Starvation and refeeding syndrome

• Hypobetalipoproteinemia

• Polycystic ovary syndrome

• Hypothyroidism

• Obstructive sleep apnea

• Total parenteral nutrition

• 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 ...