Mild isolated elevations of ALT or AST (< 2 times normal) may require only repeat testing; they resolve in about one third of cases. If abnormalities are present in other laboratory tests, are severe, or persist on subsequent testing, further evaluation is indicated as follows:

If at this point the results are negative, screening for alpha-1 antitrypsin deficiency is indicated. 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 ultrasonography 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 drugs 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 cirrhosis. Persistent unexplained elevations or suspicion of intrahepatic cholestasis warrants consideration of liver biopsy.