Workup for Transaminitis (Elevated Liver Enzymes)
The appropriate workup for transaminitis should begin with identifying common causes through targeted history, physical examination, and laboratory testing, followed by evaluation for less common etiologies if initial assessment is unrevealing.
Initial Evaluation
History and Risk Factor Assessment
- Inquire about medication use, including prescription medications, over-the-counter drugs, and herbal/dietary supplements with hepatotoxic potential 1, 2
- Obtain detailed alcohol consumption history 3
- Assess for metabolic syndrome risk factors (obesity, diabetes, hypertension) 4, 5
- Review family history of liver disease 5
- Evaluate for symptoms of viral hepatitis or autoimmune conditions 2
Physical Examination
- Check for signs of chronic liver disease (jaundice, spider angiomata, palmar erythema) 3
- Measure waist circumference and BMI to assess for metabolic syndrome 4, 5
- Examine for hepatomegaly, splenomegaly, or ascites 2
Initial Laboratory Testing
- Complete blood count with platelets 2, 5
- Comprehensive metabolic panel including AST, ALT, alkaline phosphatase, GGT, bilirubin, albumin 4, 1
- Fasting lipid profile and glucose 4, 5
- Hepatitis B surface antigen and hepatitis C antibody 4, 5
- Iron studies (serum iron, ferritin, total iron-binding capacity) 2, 5
Further Evaluation Based on Severity
Mild Elevation (< 3× ULN)
- If metabolic risk factors are present, evaluate for non-alcoholic fatty liver disease (NAFLD) 4, 5
- Monitor liver enzymes every 1-2 weeks 1
- Consider lifestyle modifications (weight loss, exercise, alcohol cessation) if initial workup suggests NAFLD or alcoholic liver disease 5
Moderate Elevation (3-5× ULN)
- Discontinue potential hepatotoxic medications if medically feasible 1
- Increase monitoring frequency to every 3 days 1
- Consider additional testing for less common causes 2
Severe Elevation (> 5× ULN)
- Urgent hepatology consultation 1
- Consider hospitalization, especially if > 20× ULN 1
- Evaluate for acute liver failure (INR, mental status) 1
Additional Testing for Persistent or Unexplained Transaminitis
Imaging
- Abdominal ultrasonography to assess for fatty infiltration, cirrhosis, or other structural abnormalities 2, 5
Testing for Less Common Causes
- Alpha-1-antitrypsin level 2, 5
- Ceruloplasmin (Wilson disease) 2, 5
- Autoimmune markers (antinuclear antibody, smooth muscle antibody, liver/kidney microsomal antibody) 2, 6
- Thyroid function tests 2, 5
- Celiac disease antibodies 5
- Creatine kinase (to rule out muscle disorders) 5
Special Considerations
Drug-Induced Liver Injury
- Withhold suspected hepatotoxic medications 1
- For patients on medications requiring liver monitoring (e.g., methotrexate), regular liver function tests are recommended 4
- Consider medication rechallenge at lower doses only after complete normalization of liver enzymes 1
Alcoholic Liver Disease
- Typical pattern shows AST > ALT (often 2:1 ratio) 3
- Complete abstinence from alcohol is recommended 3
- Evaluate for other complications of alcoholism 3
Non-Alcoholic Fatty Liver Disease
- Most common cause of mild transaminitis in developed countries 4, 5
- Calculate NAFLD fibrosis score to assess risk of advanced fibrosis 5
- Management focuses on metabolic syndrome treatment 4
When to Consider Liver Biopsy
- Persistently elevated transaminases (> 6 months) despite negative workup 2, 6
- Suspected autoimmune hepatitis or other specific diagnoses requiring histological confirmation 6
- Discordance between clinical, laboratory, and imaging findings 2
Follow-up Recommendations
- For mild, unexplained transaminitis: repeat liver enzymes in 2-4 weeks 4
- If transaminases normalize: consider case resolved or continue monitoring based on clinical context 2
- If transaminases remain elevated after 3-6 months despite negative workup and lifestyle modifications: refer to hepatology 2, 5