From the Guidelines
The appropriate workup for hypertransaminasemia (elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST)) involves classifying the severity of abnormal aminotransferase levels and considering the patient's clinical context.
Classification of Severity
- Mild: <5 times the upper reference limit
- Moderate: 5 to 10 times the upper reference limit
- Severe: >10 times the upper reference limit 1
Initial Evaluation
The initial evaluation should include a thorough medical history, physical examination, and laboratory tests to determine the underlying cause of the elevated liver enzymes.
- Laboratory tests: should include ALT, AST, alkaline phosphatase (ALP), and bilirubin levels, as well as albumin and prothrombin time to assess hepatocellular synthetic function 1
- Imaging studies: may be necessary to evaluate for liver damage or disease, such as ultrasound or CT scans
Considerations for Eligibility Criteria
In clinical trials, eligibility criteria often focus on ALT levels, with a threshold of ALT <3× ULN for eligibility in the absence of primary liver tumor or liver metastatic disease, or <5× ULN in the presence of primary liver tumor or liver metastatic disease 1
Management
Management of hypertransaminasemia depends on the underlying cause and severity of the condition.
- Mild elevations: may not require immediate intervention, but should be monitored closely
- Moderate to severe elevations: may require further evaluation and treatment, such as discontinuation of potentially hepatotoxic medications or treatment of underlying liver disease 1
From the Research
Initial Evaluation
The initial evaluation of hypertransaminasemia (elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST)) should include a thorough history and physical examination to identify potential causes 2, 3.
Common Causes
The most common causes of mild elevations in transaminase levels are:
- Nonalcoholic fatty liver disease, which can affect up to 30 percent of the population 2
- Alcoholic liver disease
- Medication-associated liver injury
- Viral hepatitis (hepatitis B and C)
- Hemochromatosis
Initial Testing
Initial testing should include:
- A fasting lipid profile
- Measurement of glucose, serum iron, and ferritin
- Total iron-binding capacity
- Hepatitis B surface antigen and hepatitis C virus antibody testing 2
Further Testing
If initial test results are normal, further testing may include:
- Ultrasonography
- Measurement of α(1)-antitrypsin and ceruloplasmin
- Serum protein electrophoresis
- Antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing 2
Referral and Liver Biopsy
Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 2, 3
Nonhepatic Causes
Nonhepatic causes of elevated liver transaminase levels should also be considered, including: