The Asymptomatic Patient With Abnormal Liver Test Results

Mild isolated elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST; < 2 times normal) may require only repeat testing; they resolve in approximately one-third of cases. It is important to clarify whether laboratory tests were performed in the fasting state because oral intake can cause mild elevations in liver tests. If abnormalities are present in other laboratory test results, are severe, or persist on subsequent testing, further evaluation is indicated as follows:

• Steatotic liver disease should be considered in patients with metabolic syndrome; it can often be recognized clinically.

• All patients should be asked about history of alcohol use.

• Patients should be screened for hepatitis B and C.

• Patients > 40 years of age should be screened for hemochromatosis.

• Patients < 30 years of age should be screened for Wilson disease.

• Most patients, especially young or middle-aged women, should be screened for autoimmune disorders.

• Patients at risk should be screened for malaria and schistosomiasis.

• Patients with early-onset obstructive lung disease (especially in the absence of smoking history) or those with cryptogenic LFT elevations should be screened for alpha-1 antitrypsin deficiency.

• Most patients should be screened for celiac disease.

• All patients should have a thorough review of all prescription medications, herbals, supplements, energy drinks, and recent antibiotics to exclude drug-induced liver injury.

• Abdominal ultrasound with Doppler can evaluate for steatotic liver disease, cirrhosis, biliary issues, and portal and hepatic vein thrombus.

If the entire evaluation reveals no cause, liver biopsy may be warranted.

Isolated elevation of alkaline phosphatase levels in an asymptomatic patient requires confirmation of hepatic origin by showing elevation of 5´-nucleotidase or gamma-glutamyl transpeptidase. If hepatic origin is confirmed, liver imaging, usually with ultrasound or magnetic resonance cholangiopancreatography, is indicated.

If no structural abnormality is found on imaging, intrahepatic cholestasis is possible and may be suggested by a history of exposure to certain medications, other substances, or toxins. Infiltrative diseases and liver metastases (eg, due to colon cancer) should also be considered. In women, antimitochondrial antibody should be obtained to check for primary biliary cholangitis. Persistent unexplained elevations or suspicion of intrahepatic cholestasis warrants consideration of liver biopsy.

Asymptomatic elevations in bilirubin should be further evaluated by differentiating whether the patient has an indirect or direct hyperbilirubinemia, because the need for additional work-up will vary based on this. In asymptomatic patients, most often this will be an indirect hyperbilirubinemia, which is usually related to a benign disorder (eg Gilbert syndrome). It is important to exclude indirect hyperbilirubinemia from hemolysis, thus a hemoglobin should always be ordered. A finding of anemia should prompt additional workup for hemolytic disorders as well as a hematology consultation. Lastly, some medications can cause hyperbilirubinemia. Any direct hyperbilirubinemia or symptomatic patients with indirect hyperbilirubinemia should be further evaluated.

See also Jaundice, Inborn Disorders of Bilirubin Metabolism, and Tests for Liver Injury.