From the Guidelines
Mildly elevated liver enzymes after ruling out HBV and HCV require a thorough workup to determine the underlying cause.
Next Diagnostic Steps
- Review medications and supplements that may cause hepatotoxicity and rule out abnormal liver enzymes from development or progression of liver metastases 1
- Check for other causes of elevated liver enzymes, such as viral hepatitis, alcohol history, iron studies, thromboembolic event, or potential liver metastasis from primary malignancy by doing blood work and imaging (ultrasound and cross-sectional imaging) 1
- Consider checking CK for other etiologies, such as muscle injury or rhabdomyolysis, especially if there is an isolated elevation of transaminases 1
- Perform a thorough history of symptoms, co-existing medical conditions, concomitant medications, dietary and nutritional supplements, excessive exercise or muscle injury, alcohol consumption, and illicit substances 1
- Consider additional tests, such as ANA, ASMA, and ANCA, if there is a high suspicion of primary autoimmune hepatitis 1
- Hepatobiliary imaging, such as ultrasonography, CT scan, MRI, or MRCP, may be necessary to evaluate the liver and bile ducts 1
- Liver biopsy should be considered if the patient is steroid-refractory or if there is a concern for other differential diagnoses that would alter medical management 1
Important Considerations
- Alcohol consumption should be assessed, as it can cause liver damage 1
- Metabolic risk factors, such as diabetes, obesity, dyslipidemia, and arterial hypertension, should be evaluated, as they can increase the risk of chronic liver disease 1
- Noninvasive tests of liver fibrosis, such as FIB-4, can be used to screen for advanced fibrosis or cirrhosis in patients with metabolic risk factors 1
From the Research
Diagnostic Approach
After ruling out Hepatitis B (HBV) and Hepatitis C (HCV), the next diagnostic step for mildly elevated liver enzymes involves a stepwise evaluation based on the prevalence of diseases that cause mild elevations in transaminase levels 2, 3.
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 (already done in this case)
Further Evaluation
If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate 2, 3. 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
Considerations
It is essential to consider extrahepatic conditions that can cause elevated liver transaminase levels, such as thyroid disorders, celiac disease, hemolysis, and muscle disorders 2, 4. Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more 2.