What does elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) indicate?

Evaluation and Management of Elevated AST and ALT

Elevated AST (aspartate aminotransferase) and ALT (alanine aminotransferase) indicate liver cell injury and require a systematic diagnostic approach to identify the underlying cause, with ALT being more specific for liver damage than AST. 1

Initial Assessment and Classification

Elevated liver enzymes can be classified based on severity:

• Mild: <5× upper limit of normal (ULN)
• Moderate: 5-10× ULN
• Severe: >10× ULN 1

Key Diagnostic Clues

• AST:ALT ratio provides valuable diagnostic insights:

  • Ratio ≥2: Strongly suggests alcoholic liver disease
  • Ratio ≥1 with chronic HCV: High specificity for cirrhosis
  • Ratio <1: Common in NAFLD/NASH 1, 2

• Pattern of elevation:

  • AST >500 IU/L or ALT >200 IU/L is uncommon in alcoholic hepatitis and should prompt consideration of other etiologies 1
  • Normal or near-normal ALT does not exclude NASH 2

Systematic Diagnostic Approach

1. Complete Laboratory Evaluation

• Full liver panel including:
  • Bilirubin (total and direct)
  • Alkaline phosphatase
  • GGT
  • Albumin
  • Prothrombin time/INR 1

2. Viral Hepatitis Screening

• Hepatitis A, B, and C testing:
  • Anti-HAV IgM
  • HBsAg
  • Anti-HBc IgM
  • HCV antibody 1

3. Medication and Toxin Review

• Review all medications (prescription, OTC, supplements)
• Assess alcohol consumption 1, 3

4. Imaging Studies

• Abdominal ultrasound as first-line imaging to:
  • Assess liver structure
  • Rule out biliary obstruction
  • Evaluate for fatty infiltration 1

5. Fibrosis Assessment

• FIB-4 score as first step
• Liver elastography if fibrosis is suspected 1

6. Additional Testing Based on Clinical Suspicion

• Autoimmune markers (ANA, ASMA, immunoglobulin levels) if autoimmune hepatitis suspected
• Iron studies for hemochromatosis
• Ceruloplasmin for Wilson's disease
• Alpha-1 antitrypsin levels 1

Common Causes of Elevated AST and ALT

1. Non-alcoholic fatty liver disease (NAFLD)/NASH

   • Most common cause in patients with metabolic syndrome or diabetes
   • Up to 80% of NASH patients may have elevated transaminases 2, 3

2. Alcoholic liver disease

   • Characterized by AST:ALT ratio ≥2 1

3. Viral hepatitis

   • Chronic hepatitis B and C
   • Enzyme elevation may not correlate with degree of liver damage 3

4. Drug-induced liver injury

   • Including immune checkpoint inhibitors which can cause severe elevations 2

5. Non-hepatic causes

   • Myocardial infarction (primarily AST)
   • Muscle injury/polymyositis
   • Hypothyroidism 3, 4

6. COVID-19 infection

   • Elevated AST in approximately 26% and ALT in 19% of patients
   • Higher prevalence in ICU-treated patients 5

7. Trauma

   • In pediatric blunt abdominal trauma, AST >450 IU/L and ALT >250 IU/L are highly sensitive and specific for liver injury 6

Management Recommendations

General Approach

• For mild elevations without clear cause, repeat testing in 2-4 weeks
• For moderate to severe elevations, more urgent evaluation is needed 1

Specific Interventions

• Lifestyle modifications for NAFLD/NASH:

  • Mediterranean diet
  • Regular exercise
  • Weight loss 1

• Complete alcohol cessation for alcoholic liver disease 1

• Medication management:

  • Identify and discontinue potential hepatotoxic medications
  • For immune checkpoint inhibitor-related elevations:
    • Grade 1 (ALT/AST > ULN – 3× ULN): Continue treatment with monitoring
    • Grade 2 (ALT/AST > 3–5× ULN): Withhold treatment and monitor
    • Grade 3-4 (ALT/AST > 5× ULN): Discontinue treatment and initiate close monitoring 2, 1

Monitoring

• For mild elevations (Grade 1): Repeat blood tests within 1-2 weeks
• For moderate to severe elevations: Repeat tests within 2-5 days 2
• For patients on medications affecting liver enzymes: Monitor CBC and LFTs within first 1-2 months and every 3-4 months thereafter 1

Referral to Hepatology

Refer to a hepatologist if:

• Liver function tests remain elevated after 3-6 months despite interventions
• Signs of hepatic decompensation are present
• Suspected autoimmune hepatitis
• ALT elevation >5× ULN
• Development of jaundice
• Elevated bilirubin with elevated transaminases 1

Pitfalls to Avoid

1. Do not assume normal ALT excludes liver disease - NASH can present with normal or near-normal ALT 2

2. Do not focus solely on liver causes - Remember non-hepatic sources of elevated enzymes, particularly AST which is present in cardiac and skeletal muscle 4

3. Do not underestimate mild elevations - Even mild elevations can indicate significant underlying liver disease 1

4. Do not delay evaluation of severe elevations - AST/ALT >10× ULN requires prompt evaluation 1

5. Do not miss medication-related causes - A thorough medication review is essential 1, 3