What is the workup for a patient with elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST)?

Workup for Elevated ALT and AST

A comprehensive workup for elevated ALT and AST should begin with testing for common hepatic diseases through blood work and imaging, followed by targeted investigations based on initial findings. 1

Initial Assessment

History and Risk Factor Evaluation

• Medication review (prescription, over-the-counter, supplements)
• Alcohol consumption history
• Risk factors for viral hepatitis
• Family history of liver disease
• Presence of metabolic syndrome components
• Symptoms of liver disease (fatigue, jaundice, abdominal pain, etc.)

Laboratory Testing

• Complete liver panel:
  • ALT, AST levels and pattern (ratio)
  • Alkaline phosphatase (ALP)
  • Gamma-glutamyl transferase (GGT)
  • Total and direct bilirubin
  • Albumin
  • Prothrombin time/INR

First-Line Investigations

1. Viral hepatitis serologies:

   • Hepatitis A IgM
   • Hepatitis B surface antigen, core antibody (IgM fraction)
   • Hepatitis C antibody (consider HCV RNA) 1

2. Abdominal imaging:

   • Ultrasound is first-line
   • Consider CT or MRI based on clinical scenario 1

Further Evaluation Based on Severity

For Mild Elevations (ALT/AST < 5× ULN)

• Discontinue potential hepatotoxic medications
• Alcohol cessation if applicable
• Consider additional testing based on clinical suspicion:
  • Iron studies (hemochromatosis)
  • Autoimmune markers (ANA, ASMA, ANCA)
  • Ceruloplasmin (Wilson's disease)
  • Alpha-1 antitrypsin levels
  • Thyroid function tests
  • Creatine kinase (for isolated transaminase elevation) 1

For Moderate to Severe Elevations (ALT/AST > 5× ULN)

• More urgent and comprehensive evaluation
• Consider hospitalization for ALT/AST > 8× ULN with elevated bilirubin 1
• Daily or every other day monitoring of liver tests
• Consider liver biopsy if etiology remains unclear 1

Special Considerations

Pattern Recognition

• Hepatocellular pattern: Predominant elevation of ALT/AST compared to ALP
  • Focus on viral hepatitis, NAFLD, alcohol, medications, autoimmune hepatitis
• Cholestatic pattern: Predominant elevation of ALP compared to ALT/AST
  • Focus on biliary obstruction, primary biliary cholangitis, primary sclerosing cholangitis 2

Medication-Induced Liver Injury

• If suspected, calculate ALT/LDH ratio:
  • Ratio >1.5 suggests viral hepatitis
  • Ratio <1.5 suggests ischemic or drug-induced injury 3

Immune Checkpoint Inhibitor Therapy

For patients on immunotherapy:

• Grade 1 (ALT/AST 1-3× ULN): Continue treatment with close monitoring
• Grade 2 (ALT/AST 3-5× ULN): Hold treatment, monitor every 3 days
• Grade 3-4 (ALT/AST >5× ULN): Consider permanent discontinuation, start steroids 1

Follow-up

• For unexplained mild elevations: Repeat testing in 2-4 weeks
• For persistent unexplained elevations (>6 months): Consider liver biopsy 1
• For improving values: Continue monitoring until normalization

Common Pitfalls to Avoid

1. Failing to consider non-hepatic causes of elevated transaminases:

   • Muscle injury (check creatine kinase)
   • Myocardial infarction
   • Thyroid disorders 4

2. Overlooking medication-induced liver injury - comprehensive medication review is essential

3. Premature attribution to NAFLD without excluding other causes

4. Missing hemolysis as a cause of hyperbilirubinemia (check direct vs. indirect bilirubin)

5. Delaying evaluation of markedly elevated enzymes or those with signs of hepatic dysfunction (elevated bilirubin, low albumin, prolonged INR)

Remember that the degree of ALT/AST elevation does not always correlate with the severity of liver damage, particularly in chronic viral hepatitis 4. A structured approach based on the pattern and degree of elevation will guide appropriate management and improve outcomes.