What does an elevated Aspartate Aminotransferase (AST) level indicate?

Elevated AST Levels: Diagnostic Implications and Evaluation

An elevated Aspartate Aminotransferase (AST) level primarily indicates hepatocellular injury, but unlike ALT, it can also reflect damage to cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells. 1

Understanding AST Elevation

AST is concentrated in the liver, but its presence in multiple tissues makes it less liver-specific than ALT:

• AST elevations indicate liver damage when accompanied by ALT elevations, but isolated AST elevations may suggest non-hepatic causes including hemolysis, myopathy, thyroid disease, or excessive exercise 1
• Normal AST levels vary by laboratory, but significant elevations are categorized as:
  • Mild: <5 times the upper reference limit
  • Moderate: 5-10 times the upper reference limit
  • Severe: >10 times the upper reference limit 1

Common Causes of Elevated AST

Hepatic Causes:

• Nonalcoholic fatty liver disease (NAFLD) - most common cause in developed countries 1
• Alcohol-induced liver disease - typically shows AST:ALT ratio >2 1
• Viral hepatitis (acute or chronic) 1
• Drug-induced liver injury 1
• Cirrhosis 1
• Ischemic hepatitis 1
• Autoimmune hepatitis 1
• Hereditary conditions (Wilson disease, hemochromatosis, alpha1-antitrypsin deficiency) 1

Non-Hepatic Causes:

• Cardiac muscle injury (myocardial infarction) 2
• Skeletal muscle damage 1, 2
• Hemolysis 1
• Macro-AST (benign condition where AST forms large complexes) 3

Diagnostic Approach to Elevated AST

When evaluating elevated AST, consider:

1. Pattern of elevation:

   • AST:ALT ratio >2 suggests alcoholic liver disease 1
   • AST:ALT ratio <1 suggests metabolic-related fatty liver disease 1
   • Isolated AST elevation may indicate non-hepatic sources 1

2. Severity of elevation:

   • Mild elevations (<5× ULN) commonly seen in NAFLD, alcohol-related liver disease 1
   • Severe elevations (>10× ULN) suggest acute viral hepatitis, drug toxicity, or ischemic injury 1, 4
   • AST >500 IU/L is uncommon in alcoholic hepatitis unless accompanied by other conditions 1

3. Associated laboratory findings:

   • Evaluate ALT, alkaline phosphatase, bilirubin, albumin, and prothrombin time 1
   • Consider ALT/LD ratio - viral hepatitis typically has ratio >1.5, while ischemic injury has ratio <1.5 4

Special Considerations

• In Wilson disease, AST may be higher than ALT, with low alkaline phosphatase and alkaline phosphatase/total bilirubin ratio <2 1
• Persistent isolated AST elevation without other abnormalities may indicate macro-AST, which can be confirmed with polyethylene glycol precipitation tests 3
• In drug-induced liver injury, AST elevations ≥3× ULN with symptoms (fatigue, nausea, right upper quadrant pain) typically warrant drug discontinuation 1
• In clinical trials, AST thresholds for action depend on baseline values, with different approaches for those with normal vs. abnormal baseline levels 1

Pitfalls to Avoid

• Don't assume all AST elevations indicate liver disease - consider non-hepatic sources 1, 2
• Don't overlook alcohol as a cause even with modest AST elevations - the AST:ALT ratio >2 is highly suggestive 1
• Don't rely solely on AST for liver function assessment - true liver function is better assessed with albumin and prothrombin time 1
• Don't miss Wilson disease in younger patients with apparent autoimmune hepatitis features - all children and non-responsive adults with presumed autoimmune hepatitis should be evaluated for Wilson disease 1