From the Guidelines
The workup for elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels should begin with a thorough history and physical examination, followed by first-line testing including serum creatine kinase, hepatitis A, B, and C testing, autoantibody and immunoglobulin testing, and hepatobiliary imaging, as recommended by the most recent guidelines 1. The initial evaluation should focus on identifying potential causes of the elevated liver enzymes, including competing causes of abnormal liver tests such as systemic infection, ischemic or congestive hepatic injury, gallstone disease, alcoholic liver disease, muscle injury, and drug-induced liver injury. Key components of the workup include:
- Thorough history of symptoms, medical conditions, medications, and lifestyle factors
- Serum creatine kinase to rule out muscle injury
- Hepatitis A, B, and C testing to identify viral hepatitis
- Autoantibody and immunoglobulin testing to evaluate for autoimmune hepatitis
- Hepatobiliary imaging, such as ultrasonography or CT scan, to assess liver structure and rule out biliary obstruction Additional testing, such as second-line testing for EBV, CMV, HSV, and VZV, or specialized tests like liver biopsy, may be necessary in certain cases, as outlined in the guidelines 1. It is essential to prioritize the most recent and highest-quality study, which in this case is the 2024 review article on recommendations for detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients 1.
From the Research
Initial Evaluation
The initial evaluation for elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels includes:
- Complete blood cell count with platelets
- Blood glucose
- Lipid profile
- Hepatitis B surface antigen
- Hepatitis C antibody
- Serum albumin
- Iron
- Total iron-binding capacity
- Ferritin 2, 3, 4
- Assessment for metabolic syndrome and insulin resistance, such as waist circumference, blood pressure, fasting lipid level, and fasting glucose or A1C level 3
Further Testing
If the initial evaluation is inconclusive, further testing may be necessary, including:
- FIB-4 Index Score or NAFLD Fibrosis Score to predict fibrosis in patients with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) 2
- Nonalcoholic fatty liver disease fibrosis score and the alcoholic liver disease/nonalcoholic fatty liver disease index to evaluate mildly elevated transaminase levels 3
- Hepatic ultrasonography if testing for common causes is consistent with nonalcoholic fatty liver disease and is otherwise unremarkable 3
- Measurement of α(1)-antitrypsin and ceruloplasmin, serum protein electrophoresis, and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing for less common causes 4
Referral and Follow-up
Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 4 All patients with elevated transaminases should be counseled about moderation or cessation of alcohol use, weight loss, and avoidance of hepatotoxic drugs 2