Laboratory Workup for Elevated Liver Function Tests
When elevated LFTs are discovered, order a comprehensive initial panel including: complete blood count, comprehensive metabolic panel (electrolytes, BUN, creatinine), fasting glucose, lipid profile, viral hepatitis markers (HBsAg, anti-HBc, anti-HCV), autoimmune markers (ANA, anti-smooth muscle antibody, anti-mitochondrial antibody), iron studies (ferritin, transferrin saturation), and abdominal ultrasound. 1, 2
Initial Comprehensive Laboratory Panel
The American College of Radiology recommends a broad initial workup that includes 1:
- Complete blood count (CBC) - to assess for cytopenias suggesting advanced liver disease or hypersplenism 1
- Comprehensive metabolic panel - including electrolytes, BUN, creatinine, glucose 1
- Lipid profile - particularly relevant for suspected NAFLD 1
- Thyroid-stimulating hormone (TSH) - thyroid dysfunction can affect liver enzymes 1
- Serum creatine kinase (CK) - essential to rule out muscle injury as a cause of elevated AST 1
Pattern Determination Tests
Measure both aminotransferases (ALT, AST) and cholestatic markers (alkaline phosphatase, GGT, bilirubin) to determine whether the pattern is hepatocellular, cholestatic, or mixed. 1, 2
This pattern guides subsequent testing:
For Hepatocellular Pattern (Elevated ALT/AST):
- Viral hepatitis markers: anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV 1, 2
- Alcohol consumption history - detailed quantification 1
- Medication and supplement review - including over-the-counter products 1
- Iron studies: ferritin and transferrin saturation for hemochromatosis 2
- Ceruloplasmin - if Wilson's disease suspected (age <40) 2
For Cholestatic Pattern (Elevated ALP/GGT):
- Anti-mitochondrial antibody (AMA) - for primary biliary cholangitis 2
- Abdominal ultrasound - to evaluate biliary system and rule out obstruction 2
- Consider MRCP if ultrasound suggests biliary pathology 2
For Mixed or Unclear Patterns:
- Autoimmune markers: ANA, anti-smooth muscle antibody, anti-LKM antibody, immunoglobulins (IgG) 2
- Alpha-1 antitrypsin level and phenotype 2
Imaging Studies
Abdominal ultrasound is recommended as part of the initial workup to evaluate liver parenchyma, assess for steatosis, exclude masses, and evaluate the biliary system. 2
The British Society of Gastroenterology emphasizes that imaging helps exclude biliary obstruction or neoplasm and should be obtained early in the evaluation 3.
Severity-Based Monitoring
The American College of Radiology classifies elevations to guide monitoring frequency 1:
- Mild (<5× ULN): Repeat weekly until normalization 1
- Moderate (5-10× ULN): Monitor every 2-3 days until stable 1
- Severe (10-20× ULN): Monitor every 2-3 days, consider hospitalization 1
- Life-threatening (>20× ULN): Immediate hospitalization with intensive monitoring 1
Common Pitfalls to Avoid
- Don't assume elevated AST is hepatic - always check CK to exclude rhabdomyolysis or muscle injury 1
- Don't order tests in isolation - a panel approach is more cost-effective and has better sensitivity/specificity than individual tests 4
- Don't forget medication history - obtain detailed list including prescription drugs, over-the-counter medications, herbal supplements, and recent antibiotic use 1
- Don't delay ultrasound - biliary obstruction and structural lesions require early imaging identification 2
Referral Criteria
Refer to hepatology or gastroenterology if: 1, 2
- ALT persistently >5× ULN 1
- Positive viral hepatitis markers (HBsAg, anti-HCV) 2
- Positive autoimmune markers suggesting autoimmune hepatitis or PBC 2
- Evidence of advanced fibrosis or cirrhosis 1
- Etiology remains unclear after comprehensive workup 2
- Unexplained jaundice or suspicion of malignancy 2
Timeline for Repeat Testing
If initial workup is unrevealing and LFTs remain mildly elevated, the British Society of Gastroenterology suggests 3-6 months of observation with repeat testing before proceeding to liver biopsy 3, 5. During this period, eliminate potential hepatotoxins and address metabolic risk factors 5.