From the Guidelines
For elevated AST and ALT, I recommend ordering a comprehensive liver panel including alkaline phosphatase, bilirubin (total and direct), gamma-glutamyl transferase (GGT), albumin, and prothrombin time to assess liver function, as suggested by the most recent guidelines 1.
Initial Evaluation
The initial evaluation of abnormal liver tests includes a detailed history, inventory of medications, and a physical examination, as outlined in the American Gastroenterological Association medical position statement 1. This should include an assessment of the patient’s risk factors for liver disease, medications, alcohol consumption, comorbid conditions, and signs and symptoms of hepatic disease.
Laboratory Tests
Additional tests should include:
- Hepatitis serologies (A, B, and C)
- Autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody)
- Iron studies (ferritin, transferrin saturation)
- Ceruloplasmin for Wilson's disease
- Alpha-1 antitrypsin levels These tests help identify the underlying cause of liver enzyme elevation, which could range from viral hepatitis and medication effects to autoimmune conditions and metabolic disorders, as discussed in the Journal of the American College of Radiology 1.
Imaging Studies
An abdominal ultrasound should be performed to evaluate liver structure and rule out biliary obstruction, as recommended by the European Association for the Study of the Liver 1. If alcohol use is suspected, check carbohydrate-deficient transferrin. For patients with risk factors, consider testing for non-alcoholic fatty liver disease. In cases with significant elevation or persistent abnormalities, further imaging like CT or MRI may be necessary.
Non-Invasive Fibrosis Tests
Non-invasive fibrosis tests, such as FIB-4, should be used to rule out advanced fibrosis in low-prevalence populations, as suggested by the European Association for the Study of the Liver 1. These tests can help identify patients at risk of advanced liver fibrosis and prompt further testing for those with indeterminate and positive results.
Clinical Context
The interpretation of all abnormal liver chemistries must be taken in the clinical context of a given patient, as emphasized in the American Gastroenterological Association medical position statement 1. The algorithm approach is useful mainly when there are no clinical clues or when the suspected diagnosis cannot be verified. A decision about the need for further diagnostic evaluation and/or the appropriate evaluation can best be made based on the specific clinical scenario of the individual patient.
From the Research
Evaluation of Elevated AST and ALT
To evaluate elevated AST and ALT levels, the following tests can be ordered:
- Viral hepatitis panel to test for hepatitis A, B, and C 2
- Assessment for nonalcoholic fatty liver disease and alcoholic liver disease 2
- Screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 2
- Testing for primary biliary cholangitis and primary sclerosing cholangitis if the alkaline phosphatase elevation is determined to be of hepatic origin 2
- Fractionation of total bilirubin elevation to direct and indirect bilirubin fractions to determine if it is due to hepatocellular disease or biliary obstruction 2
- Liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 2
Specific Considerations
- HCV infection is closely associated with elevated ALT levels, and ALT screening remains a simple and valuable method in the early recognition of HCV infection 3
- HBV infection plays a minor role in the etiology of raised ALT activity among drug abusers 3
- The degree of elevation of ALT and/or AST in the clinical setting helps guide the evaluation 2