From the Guidelines
Elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels should be evaluated 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. The evaluation of patients with elevated AST and ALT levels is crucial to determine the underlying cause of liver injury, which can be due to various factors such as drug-induced liver injury, viral hepatitis, autoimmune hepatitis, or other conditions 1.
Initial Evaluation
The initial evaluation should include:
- A thorough history of symptoms, medical conditions, medications, and lifestyle factors
- Serum creatine kinase to rule out muscle injury or rhabdomyolysis
- Hepatitis A, B, and C testing to diagnose acute or chronic viral hepatitis
- Autoantibody and immunoglobulin testing to evaluate for autoimmune hepatitis
- Hepatobiliary imaging such as ultrasonography, CT scan, or MRI to assess for structural abnormalities or biliary obstruction
Additional Testing
Additional testing may be necessary based on the initial evaluation, including:
- Second-line testing for EBV, CMV, HSV, and VZV to diagnose hepatic injury caused by these viruses
- Liver biopsy to determine the pattern and severity of liver injury
- Alcohol testing to evaluate for alcohol-related liver disease
- Acetaminophen level and protein adducts to diagnose acetaminophen toxicity
- Review of blood pressure, pulse, electrocardiogram, and echocardiogram to evaluate for ischemic or congestive hepatic injury
Importance of Early Evaluation
Early evaluation and diagnosis of the underlying cause of elevated AST and ALT levels are essential to prevent further liver damage and improve patient outcomes 1. A comprehensive evaluation and management plan can help identify the cause of liver injury and guide treatment decisions.
Patient Management
While awaiting test results, patients should avoid alcohol, review all medications for potential hepatotoxicity, and maintain a healthy diet low in processed foods and sugars. Lifestyle modifications such as weight loss and exercise should be initiated if the patient has risk factors for fatty liver disease. Follow-up testing in 4-6 weeks is appropriate to monitor trends in liver enzymes after interventions have been implemented.
From the Research
Evaluation of Elevated AST and ALT Levels
Elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels can be caused by various factors, including:
- Chronic alcohol consumption, drugs, non-alcoholic steatohepatitis (NASH), and chronic viral hepatitis 2
- Non-hepatic causes such as polymyositis, acute muscle injury, acute myocardial infarction, and hypothyroidism 2
- Immune checkpoint inhibitors (ICI) used in cancer therapy, which can cause liver enzyme elevation due to immunotoxicity 3
- Other conditions such as thyroid disorders, celiac disease, hemolysis, and muscle disorders 4
Diagnostic Approach
The diagnostic approach for elevated AST and ALT levels involves:
- Obtaining a complete history regarding risk factors for viral hepatitis, substance abuse, and requesting investigations accordingly 2
- Initial testing including a fasting lipid profile, measurement of glucose, serum iron, and ferritin, total iron-binding capacity, and hepatitis B surface antigen and hepatitis C virus antibody testing 4
- Further testing for less common causes, such as ultrasonography, measurement of α(1)-antitrypsin and ceruloplasmin, serum protein electrophoresis, and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing 4
- Referral for further evaluation and possible liver biopsy if transaminase levels remain elevated for six months or more 4
Predictive Value of ALT Levels
The predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD) is limited, with no optimal ALT level to predict NASH and advanced fibrosis 5