What does elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) indicate and how is it managed?

Management of Elevated AST and ALT

Elevated AST and ALT levels indicate hepatocellular injury and require a systematic diagnostic approach based on the severity of elevation, with nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease being the most common causes of mild elevations. 1

Classification of Aminotransferase Elevations

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

Common Causes of Elevated Aminotransferases

Hepatic Causes

• Most common:

  • Nonalcoholic fatty liver disease (NAFLD) - prevalence 20-30% in general population, 70% in obesity, 90% in diabetes 1
  • Alcohol-induced liver disease (AST:ALT ratio typically >2) 1
  • Drug-induced liver injury (DILI)
  • Viral hepatitis (B and C)

• Less common:

  • Hemochromatosis
  • Autoimmune hepatitis
  • Alpha-1 antitrypsin deficiency
  • Wilson disease 1

Non-hepatic Causes (particularly for AST)

• Cardiac disorders (myocardial infarction)
• Skeletal muscle disorders (polymyositis)
• Thyroid disease
• Strenuous exercise 1, 2

Diagnostic Approach

Initial Evaluation

1. Determine severity of elevation:

   • Mild (<5× ULN)
   • Moderate to severe (>5× ULN) 1

2. Assess for symptoms and risk factors:

   • Fatigue, nausea, vomiting, right upper quadrant pain
   • Risk factors for viral hepatitis
   • Alcohol consumption
   • Medication history (including over-the-counter drugs)
   • Metabolic risk factors (obesity, diabetes) 1

3. Initial laboratory tests:

   • Complete liver panel (AST, ALT, alkaline phosphatase, bilirubin, albumin, prothrombin time)
   • Viral hepatitis serologies (HAV-IgM, HBsAg, HBc-IgM, HCV antibody) 1

For Mild Elevations (<5× ULN)

1. Exclude common hepatic diseases with noninvasive serologic tests
2. Consider abdominal ultrasound to assess for fatty liver, biliary obstruction, or other structural abnormalities
3. If initial tests unrevealing:
   • Consider observation with serial liver enzyme monitoring
   • Consider additional testing based on clinical suspicion 1

For Moderate to Severe Elevations (>5× ULN)

1. More expeditious and complete diagnostic evaluation
2. Consider liver biopsy if etiology remains unclear after initial evaluation
3. Interrupt any potentially hepatotoxic medications 1

Special Considerations

Patients with Abnormal Baseline Liver Tests

For patients with chronically elevated baseline enzymes (e.g., NAFLD patients):

• Use multiples of baseline rather than ULN for monitoring
• Consider ALT ≥2× baseline as significant in patients with elevated baseline enzymes
• For patients with normal/near normal baseline: ALT ≥5× ULN warrants close monitoring
• For patients with elevated baseline: ALT ≥3× baseline or ≥300 U/L (whichever occurs first) warrants close monitoring 1

Drug-Induced Liver Injury

• Suspect DILI when ALT rises significantly after starting a new medication
• For patients with normal baseline: ALT ≥3× ULN with symptoms or ≥5× ULN without symptoms warrants close monitoring
• Consider drug interruption for ALT ≥8× ULN or ALT ≥3× ULN with bilirubin ≥2× ULN 1

Management Approach

1. For asymptomatic mild elevations with no identified cause:

   • Lifestyle modifications (weight loss, exercise, alcohol cessation)
   • Serial monitoring every 3-6 months
   • Consider referral if persistent for ≥6 months 3

2. For moderate to severe elevations or symptomatic patients:

   • More urgent evaluation
   • Consider referral to hepatology
   • Management of underlying cause 1

3. For suspected NAFLD:

   • Weight loss (7-10% of body weight)
   • Management of metabolic comorbidities
   • Avoidance of alcohol 1

Important Caveats

• ALT is more liver-specific than AST, which can also be elevated in cardiac and skeletal muscle disorders 4
• The AST:ALT ratio can provide diagnostic clues (>2 in alcoholic liver disease, <1 in NAFLD) 1
• Persistent abnormalities (>6 months) warrant more thorough evaluation and possible liver biopsy 1
• Liver enzymes may not correlate with the severity of liver damage, especially in chronic viral hepatitis 2
• In COVID-19 patients, 14-53% may have LFT abnormalities, which are generally transient 1

Remember that while elevated aminotransferases indicate hepatocellular injury, they do not directly measure liver function. True liver function is better assessed by albumin, bilirubin, and prothrombin time 1.