From the Guidelines
For mildly elevated AST and ALT, a stepwise approach starting with a thorough history and physical examination is recommended to identify and address potential causes such as alcohol use, medications, obesity, and diabetes. This approach is supported by the most recent evidence from the American College of Radiology 1, which emphasizes the importance of evaluating hepatocellular predominant liver chemistry and considering nonhepatic causes of elevated aminotransferases.
Initial Evaluation
The initial evaluation should include:
- Baseline labs: complete metabolic panel, complete blood count, and coagulation studies
- Additional testing: hepatitis serology (A, B, C), iron studies, ceruloplasmin (for Wilson's disease), antinuclear antibody, anti-smooth muscle antibody, and immunoglobulin levels to evaluate for autoimmune hepatitis
- Consider ultrasound of the liver to assess for fatty liver, masses, or biliary obstruction
Lifestyle Modifications and Monitoring
If the patient has risk factors for non-alcoholic fatty liver disease (NAFLD), lifestyle modifications including weight loss, exercise, and dietary changes are first-line treatments. Monitoring should include repeat liver function tests every 3-6 months, as recommended by the American College of Radiology 1.
Referral to Gastroenterology
For persistent elevations without clear cause, consider referral to gastroenterology for possible liver biopsy, as suggested by the Journal of Clinical Oncology 1. This approach helps rule out more serious liver diseases that require specific treatment, such as autoimmune hepatitis or Wilson's disease.
Rationale
The rationale for this approach is that most mild elevations (less than 2-3 times upper limit of normal) are due to common conditions like NAFLD, medication effects, or alcohol use, but systematic evaluation helps rule out more serious liver diseases that require specific treatment, as supported by the Journal of the American College of Radiology 1.
From the Research
Workup for Mildly Elevated AST and ALT
The workup for mildly elevated AST and ALT levels involves a stepwise evaluation based on the prevalence of diseases that cause mild elevations in transaminase levels 2. The following steps can be taken:
- Obtain a complete history regarding risk factors for viral hepatitis, substance abuse, and other potential causes of liver damage 3
- Initial testing should include:
- 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
- If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate 2
- Additional 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
Common Causes of Mildly Elevated AST and ALT
The most common causes of mildly elevated AST and ALT levels include:
- Nonalcoholic fatty liver disease (can affect up to 30% of the population) 2
- Alcoholic liver disease
- Medication-associated liver injury
- Viral hepatitis (hepatitis B and C) 2, 4
- Hemochromatosis
- Less common causes include α(1)-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease 2
- Extrahepatic conditions such as thyroid disorders, celiac disease, hemolysis, and muscle disorders can also cause elevated liver transaminase levels 2, 5
Referral and Further Evaluation
Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 2. A liver biopsy may be considered when serologic testing and imaging fail to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 6.