What labs should be checked for a patient presenting with transaminitis (elevated liver enzymes)?

Laboratory Evaluation for Transaminitis (Elevated Liver Enzymes)

For patients presenting with transaminitis, a comprehensive laboratory workup should include ALT, AST, alkaline phosphatase, total and direct bilirubin, albumin, prothrombin time/INR, complete blood count, and targeted tests to identify the underlying etiology. 1

Initial Laboratory Panel

Core Liver Tests

• Liver enzymes

  • ALT (alanine aminotransferase) - more liver-specific
  • AST (aspartate aminotransferase)
  • Alkaline phosphatase (ALP)
  • Gamma-glutamyl transferase (GGT) - to confirm hepatic origin of elevated ALP

• Liver function indicators

  • Total and direct (conjugated) bilirubin
  • Albumin
  • Prothrombin time (PT)/International Normalized Ratio (INR)

• Complete blood count (CBC)

  • Platelet count (thrombocytopenia may indicate cirrhosis/portal hypertension)
  • Hemoglobin/hematocrit (anemia may be present in chronic liver disease)

Etiologic Workup Based on Pattern

For Hepatocellular Pattern (Predominantly elevated ALT/AST)

• Viral hepatitis serologies

  • Hepatitis A antibody (IgM)
  • Hepatitis B surface antigen, core antibody, surface antibody
  • Hepatitis C antibody (with reflex RNA if positive)
  • Consider other viral studies based on clinical context (EBV, CMV, HSV)

• Metabolic/genetic disorders

  • Ferritin, iron, total iron binding capacity (hemochromatosis)
  • Ceruloplasmin (Wilson's disease)
  • Alpha-1 antitrypsin level and phenotype
  • Fasting lipid panel and glucose (NAFLD assessment)

• Autoimmune markers

  • Antinuclear antibody (ANA)
  • Smooth muscle antibody (ASMA)
  • Liver-kidney microsomal antibody (anti-LKM)
  • Immunoglobulin levels (IgG, IgM, IgA)

For Cholestatic Pattern (Predominantly elevated ALP)

• Biliary tract evaluation
  • GGT (to confirm hepatic origin of ALP)
  • Antimitochondrial antibody (primary biliary cholangitis)
  • IgG4 levels (IgG4-related disease)

For Drug-Induced Liver Injury Consideration

• Review all medications and supplements
• Consider CK (creatine kinase) for isolated transaminase elevations to rule out muscle origin 1

Additional Tests Based on Clinical Context

• For suspected alcohol-related liver disease

  • AST:ALT ratio (typically >2:1)
  • Carbohydrate-deficient transferrin

• For suspected NAFLD

  • Hemoglobin A1c
  • Fasting insulin level (HOMA-IR calculation)

• For patients with immune checkpoint inhibitor therapy

  • More frequent monitoring (weekly initially, then every 2-4 weeks) 1

Monitoring Recommendations

• For mild elevations (ALT/AST <5× ULN)

  • Repeat testing in 2-4 weeks 1

• For moderate elevations (ALT/AST 5-10× ULN)

  • Repeat testing within 3-5 days 1

• For severe elevations (ALT/AST >10× ULN)

  • Immediate repeat testing within 2-3 days
  • Consider hospitalization for close monitoring 1

Special Considerations

• Pre-existing liver disease: Baseline values should be considered when interpreting results 1

• Patients on hepatotoxic medications: More frequent monitoring may be needed 1

• Patients with normal ALT but suspected liver disease: Normal values don't exclude significant liver pathology, especially NASH 1

Pitfalls to Avoid

• Relying solely on transaminase levels: Up to 50% of patients with NAFLD and some with chronic hepatitis may have normal liver enzymes 1

• Missing non-hepatic causes of elevated AST: Check CK to rule out muscle origin of elevated transaminases 1

• Premature attribution to NAFLD: Don't assume fatty liver without ruling out viral hepatitis, especially in high-risk populations 2

• Isolated interpretation of single tests: The pattern and trend of abnormalities are more informative than single values 3

By following this systematic approach to laboratory evaluation, clinicians can effectively identify the underlying cause of transaminitis and initiate appropriate management to prevent progression of liver disease.