Causes of Elevated AST (Aspartate Aminotransferase)
Elevated AST can arise from both hepatic and non-hepatic sources, with the most common hepatic causes being nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis, while non-hepatic causes include muscle injury, cardiac damage, and hemolysis. 1
Hepatic Causes
Most Common Liver-Related Causes
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of elevated liver enzymes in developed countries, affecting 20-30% of the general population and up to 70% in obese individuals, typically presenting with an AST:ALT ratio <1 1
Alcoholic liver disease characteristically shows an AST:ALT ratio >2:1, which is highly suggestive of this condition, with ratios >3 being even more specific 1, 2
Viral hepatitis (both acute and chronic) causes ALT/AST elevation, with chronic forms showing fluctuating enzyme levels particularly during reactivation phases 1
Less Common Hepatic Causes
Hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson's disease are less frequent causes of elevated liver enzymes 1
Drug-induced liver injury can cause elevated AST, with statins like pravastatin specifically documented to cause transaminase elevations 3
Non-Hepatic Causes
Muscle-Related Causes
Muscle injury or rhabdomyolysis can significantly elevate AST, confirmed by checking creatine kinase (CK) levels, which will be markedly elevated 1
Intensive exercise, particularly weight lifting, can lead to acute AST elevations due to muscle damage that may be mistaken for liver injury 1
While ALT is more liver-specific, AST is present in skeletal muscle and can be elevated with significant muscle damage 1
Cardiac and Hematologic Causes
Cardiac injury including myocardial infarction can cause AST elevation, as AST is present in cardiac muscle 2, 4
Hemolysis can elevate AST since the enzyme is present in erythrocytes 2, 4
Other Non-Hepatic Causes
Thyroid disease, particularly hypothyroidism, can cause elevated AST 2, 5
Polymyositis and acute muscle injury are additional causes 5
Diagnostic Approach by Severity
Severity Classification
- Mild elevation: <5× upper limit of normal (ULN) 1
- Moderate elevation: 5-10× ULN 1
- Severe elevation: >10× ULN 1
Initial Evaluation Strategy
For mild asymptomatic increases, consider NAFLD, dietary changes, or exercise, and use ultrasound as first-line investigation 1
Obtain detailed history regarding alcohol consumption, medications (including over-the-counter drugs, vitamins, and herbs), risk factors for viral hepatitis, and recent exercise patterns 6, 1
Check for concomitant alkaline phosphatase and bilirubin elevations to determine if the pattern is hepatocellular versus cholestatic 6
Confirming the Source of Elevation
Test creatine phosphokinase (CK), aldolase, or other muscle-related enzymes to confirm non-hepatic origin when muscle injury is suspected 1
Calculate the AST:ALT ratio: a ratio >2:1 suggests alcoholic liver disease, while <1 suggests NAFLD 1, 2
Screen for viral hepatitis with appropriate serologies (HAV-IgM, HBsAg, HBcIgM, HCV antibody) 6
Special Considerations
Macro-AST
Macro-AST is a benign condition where AST binds to immunoglobulins, creating a high-molecular-weight complex that causes persistently elevated AST without actual liver disease 7
Consider polyethylene glycol (PEG) precipitation testing in patients with isolated, persistent AST elevation when all other evaluations are negative 7
Critical Pitfalls to Avoid
AST levels >500 IU/L are uncommon in alcoholic hepatitis and should prompt consideration of other etiologies such as ischemic hepatitis, acute viral hepatitis, or drug-induced liver injury 2, 8
Mild asymptomatic increases in ALT/AST (<3× ULN) without elevated bilirubin may be related to vigorous exercise and should not automatically trigger extensive workup 1
Do not rely solely on AST:ALT ratio for diagnosis without considering the complete clinical picture and additional laboratory findings 2
Chronic viral hepatitis enzyme elevations may not correlate well with the degree of actual liver damage 5