The degree of aminotransferase elevation may point to different differentials, as well as course of management. With elevations less than 15x normal values, differentials that can be considered are chronic viral hepatitis, medications, hemochromatosis, alcoholic liver disease, thyroid disorders, adrenal insufficiency, anorexia nervosa, and more. Part of evaluating these patients would be to review medications and other possible drugs, check for alcohol abuse, draw hepatitis panels, draw serum iron and TIBC to evaluate for hemochromatosis, and potential liver U/S or CT to check for fatty liver. In well-appearing patients with elevations less than 5x normal limit, they can be monitored over 3-6 months.

With severely elevated levels, differentials can include acetaminophen toxicity, other toxin exposure, acute viral hepatitis, alcoholic/autoimmune/ischemic hepatitis, Budd Chiari syndrome, sepsis, and more. Evaluation may include getting acetaminophen levels, toxicology screening, hepatitis panel, and autoimmune markers, with possible further investigation with U/S to look for evidence of no perfusion to the liver, and liver biopsy.

Elevations 4x above normal value of ALP are typically are seen in cholestasis. Elevation due to hepatic issues can be confirmed with gamma-glutamyl transpeptidase (GGT) and serum 5′-nucleotidase levels; since their values are also elevated when there’s a liver issue and not a bone issue. As mentioned before, ALP is more associated with cholestasis, which involves the impaired formation and secretion of bile. Common causes include intra or extrahepatic occlusion of bile ducts, biliary cholangitis, sclerosing cholangitis, sarcoidosis, and certain drugs (ie: phenytoin). Initial evaluation will include RUQ U/S. From visualizing biliary dilation, it would indicate extrahepatic cholestasis. To confirm, ERCP, MRCP or CT can be done to search for what is causing the obstruction. The lack of biliary dilation on U/S would require further evaluation (antimitochondrial Ab (AMA), antinuclear Ab, antismooth muscle Ab, liver biopsy) to confirm possible causes of intrahepatic cholestasis (ie: drug toxicity, biliary cholangitis, viral hepatitis).

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