Fatty Liver Disease, Nonalcoholic

Key Features

Essentials of Diagnosis

• Hepatomegaly in patient with body mass index more than 95th percentile

• Elevated alanine aminotransferase (ALT) > aspartate aminotransferase (AST)

• Detection of fatty infiltration of the liver on ultrasound

• Histologic evidence of fat in the liver

• Insulin resistance

General Considerations

• A clinicopathologic condition of abnormal hepatic fat deposition in the absence of alcohol

• Most common cause of abnormal liver function tests in the United States

• Ranges from bland steatosis, to fat and inflammation, with or without scarring (also referred to as nonalcoholic steatohepatitis, NASH) to cirrhosis

• Incidence correlates with obesity; in the United States,

  • Up to 10% of all children are affected

  • 38% of obese children are affected

• Comorbidites include

  • Type 2 diabetes mellitus

  • Hypertension

  • Hyperlipidemia

  • Metabolic syndrome

• Most children are 11–13 years old at diagnosis

• Males (ratio of 2:1) and Hispanics at highest risk

Clinical Findings

Symptoms and Signs

• Most patients are asymptomatic

• Nonalcoholic fatty liver disease (NAFLD) often discovered on routine screening

• Some patients may complain of fatigue or right upper quadrant pain

• Obesity and insulin resistance are known risk factors

• Moderate sleep apnea is also common

• Obstructive sleep apnea and hypoxia appear to contribute to disease severity

• Asymptomatic soft hepatomegaly may be present, but abdominal adiposity may make this difficult to assess

• Physical findings of insulin resistance (acanthosis nigricans and a buffalo hump) are frequently present

Differential Diagnosis

• Wilson disease

• Hereditary fructose intolerance

• Tyrosinemia

• Hepatitis caused by hepatitis C virus

• Cystic fibrosis

• Fatty acid oxidation defects

• Kwashiorkor

• Reye syndrome

• Respiratory chain defects

• Total parenteral nutrition–associated liver disease

• Toxic hepatopathy (ethanol and others)

Diagnosis

Laboratory Findings

• AST and ALT

  • May be normal

  • Do not identify bland steatosis

  • If elevated, typically elevated < 1.5="" times="" the="" upper="" limit="" of="" normal,="" with="" an="" alt:ast="" ratio="" of=""> 1

• Alkaline phosphatase and GGT may be mildly elevated

• Bilirubin is normal

• Hyperglycemia and hyperlipidemia are also common

Imaging

• Ultrasonography, CT scan, or MRI can be used to confirm fatty infiltration of the liver

• While ultrasound costs less and lacks radiation exposure, it may be insensitive in severe central adiposity or if < 30% steatosis is present

• Radiologic imaging cannot distinguish bland steatosis from the more severe NASH or reliably identify fibrosis

• Transient elastography is a research tool that shows promise in estimating hepatic fibrosis

Diagnostic Procedure

• Liver biopsy may show

  • Microvesicular or macrovesicular steatosis

  • Hepatocyte ballooning

  • Mallory bodies

  • Lobular or portal inflammation

  • Varying degrees of fibrosis

Treatment

• Lifestyle modifications, through both dietary changes and exercise, to induce slow weight loss

• A 10% decrease in body weight can significantly improve NAFLD

Outcome

Prevention

• Weight management

Complications

• Untreated NAFLD with hepatic inflammation can progress ...