What is the workup for a patient with mildly elevated transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT))?

Workup for Mildly Elevated Transaminases

The workup for mildly elevated transaminases should begin with targeted testing for common causes including nonalcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, and medication-induced liver injury, followed by testing for less common etiologies if initial evaluation is unrevealing. 1

Initial Evaluation

History and Physical Examination Focus

• Assess risk factors for liver disease, detailed alcohol consumption history, and complete medication review (including over-the-counter drugs, supplements, and herbs) 1
• Evaluate for symptoms of chronic liver disease (fatigue, jaundice, pruritus) 1
• Assess for metabolic syndrome components (obesity, diabetes, hypertension) as risk factors for nonalcoholic fatty liver disease 1

First-Line Laboratory Testing

• Complete liver panel (AST, ALT, alkaline phosphatase, total and direct bilirubin, albumin, prothrombin time) 1
• Fasting lipid profile and glucose (to assess for metabolic syndrome) 2
• Viral hepatitis serologies: HBsAg, HBcIgM, HCV antibody 1
• Iron studies: serum iron, ferritin, total iron-binding capacity (to screen for hemochromatosis) 2
• Complete blood count (to assess for hemolysis or infection) 2

Initial Imaging

• Abdominal ultrasound - first-line imaging test for evaluating mild transaminase elevations 1
  • Highly sensitive for detecting moderate to severe hepatic steatosis (sensitivity 84.8%, specificity 93.6%) 1
  • Can identify other structural causes of liver enzyme elevation 1

Management Algorithm

If Initial Testing Suggests a Specific Diagnosis:

• Nonalcoholic fatty liver disease (NAFLD): Most common cause, affecting up to 30% of the population 2

  • Characterized by ALT > AST ratio (typically <1) 1
  • Implement lifestyle modifications (weight loss, exercise, dietary changes) 1

• Alcoholic liver disease:

  • Characterized by AST:ALT ratio >2 1
  • Recommend alcohol cessation and monitor transaminases 1

• Medication-induced liver injury:

  • Discontinue suspected hepatotoxic medications when possible 1
  • Re-evaluate transaminases after 2-4 weeks 2

• Viral hepatitis:

  • Refer for specific management based on viral etiology 1

If Initial Testing is Unrevealing:

• Consider second-line testing for less common causes 2:
  • Alpha-1 antitrypsin level 1, 2
  • Ceruloplasmin (for Wilson disease) 2
  • Autoimmune markers: ANA, smooth muscle antibody, liver/kidney microsomal antibody 2
  • Celiac disease serologies 2
  • Thyroid function tests 1
  • Creatine kinase (to rule out muscle disorders causing AST elevation) 1

Monitoring and Follow-up

• For mild elevations (<5× upper limit of normal) without identified cause:

  • Repeat liver enzymes in 2-4 weeks 1
  • If persistent elevation, continue evaluation for less common causes 1

• For identified causes:

  • Monitor response to specific interventions (e.g., lifestyle modifications for NAFLD) 1
  • Consider hepatology referral if:
    • Transaminases remain elevated for ≥6 months 2
    • Progressive elevation of transaminases despite intervention 1
    • Evidence of synthetic dysfunction (decreased albumin, prolonged prothrombin time) 1

Important Considerations

• Normal ALT ranges differ by sex: 29-33 IU/L for males and 19-25 IU/L for females 1, 3
• AST is less specific for liver injury as it can be elevated in cardiac, skeletal muscle, kidney, and red blood cell disorders 1
• Elevated transaminases are associated with increased liver-related mortality, warranting thorough evaluation even when mild 3
• AST typically decreases more rapidly than ALT during recovery from liver injury 4
• Folic acid supplementation may reduce risk of transaminase elevations in patients taking methotrexate 5