What causes elevated Alanine Transaminase (ALT) and Aspartate Transaminase (AST) levels?

Causes of Elevated ALT and AST Levels

Elevated ALT and AST levels are most commonly caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease, with viral hepatitis, drug-induced liver injury, and autoimmune conditions being other significant causes that require prompt evaluation. 1, 2

Common Causes of Elevated Transaminases

Hepatic Causes

• Nonalcoholic fatty liver disease (NAFLD): Most common cause in developed countries, associated with metabolic syndrome, obesity, and insulin resistance 1, 2
• Alcoholic liver disease: Second most common cause, related to chronic alcohol consumption 3
• Viral hepatitis:
  • Hepatitis B (HBsAg positive)
  • Hepatitis C (HCV antibody positive)
  • Other viral hepatitis (A, E) 1, 3
• Drug-induced liver injury: Various medications including acetaminophen, antibiotics, statins, and herbal supplements 4, 2
• Autoimmune hepatitis: Often associated with positive ANA, ASMA, and elevated IgG levels 4, 1

Non-Hepatic Causes

• Muscle disorders:
  • Polymyositis
  • Extreme exercise/muscle injury
  • Rhabdomyolysis 5
• Cardiac conditions:
  • Myocardial infarction (can cause AST elevation) 6, 5
• Other conditions:
  • Thyroid disorders
  • Celiac disease
  • Hemolysis 2

Diagnostic Approach

Initial Evaluation

1. First-line testing (based on clinical guidelines):

   • Complete history (medications, alcohol use, risk factors for viral hepatitis)
   • Hepatitis B serology (HBsAg, anti-HBc)
   • Hepatitis C antibody with reflex RNA testing if positive
   • Autoimmune markers (ANA, ASMA, IgG levels) if suspected
   • Serum CK (to rule out muscle injury)
   • Abdominal ultrasound 4, 1

2. Assessment for metabolic syndrome:

   • Waist circumference
   • Blood pressure
   • Fasting lipid profile
   • Fasting glucose or A1C level 1, 2

3. Additional testing:

   • Complete blood count with platelets
   • Serum albumin, iron studies (iron, TIBC, ferritin)
   • Consider HIV testing 1

Pattern Recognition

• AST/ALT ratio > 3: Suggests alcoholic liver disease or advanced cirrhosis 7
• AST/ALT ratio > 3 with elevated CK: Suggests muscle injury 5
• Persistent mild elevation (< 5× ULN): Often NAFLD or chronic viral hepatitis 2
• Severe elevation (> 20× ULN): Suggests acute viral hepatitis, drug toxicity, or ischemic injury 1

Management Considerations

When to Refer to Hepatology

• ALT/AST > 5× ULN
• ALT/AST > 3× ULN with total bilirubin ≥ 2× ULN
• Persistent elevation > 6 months despite interventions
• Development of symptoms (jaundice, abdominal pain, fatigue) 1

Monitoring Recommendations

• Mild elevations: Every 1-3 months
• Moderate elevations: Every 2-3 weeks
• Severe elevations: 2-3 times weekly 1

Important Clinical Pitfalls

1. Don't assume all elevations are liver-related: Check CK to rule out muscle disorders, especially with AST > ALT 5

2. Don't repeatedly test without diagnostic workup: Delayed diagnosis may lead to disease progression 1

3. Don't overlook non-hepatic causes: Thyroid disorders, celiac disease, and muscle conditions can all cause transaminase elevations 2

4. Remember that enzyme levels may not correlate with disease severity: In chronic viral hepatitis, normal or mildly elevated enzymes can still indicate significant liver damage 3

5. Consider country of origin: This is the strongest predictor of viral hepatitis, more so than ethnic group 1