AST and ALT: Essential Liver Enzymes for Disease Detection and Management
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are critical liver enzymes whose levels help diagnose, classify, and monitor liver diseases, with ALT being the more liver-specific marker while AST is also found in cardiac tissue, skeletal muscle, and erythrocytes. 1, 2
What Are AST and ALT?
AST (Aspartate Aminotransferase):
- Present in liver tissue, cardiac and skeletal muscle, and erythrocytes
- Less specific for liver damage due to its presence in multiple tissues
- Often measured alongside ALT to calculate the AST/ALT ratio
ALT (Alanine Aminotransferase):
- Predominantly found in liver tissue
- More specific marker for liver damage
- Considered the most reliable biomarker for liver diseases 3
Clinical Importance
1. Diagnostic Value
- Help detect liver injury and distinguish between different liver diseases
- Pattern of elevation helps classify liver injury as 4:
- Hepatocellular (R ≥5): Primarily affecting liver cells
- Cholestatic (R ≤2): Primarily affecting bile flow
- Mixed (R between 2-5): Combined features
2. AST/ALT Ratio - Critical Diagnostic Tool
- AST/ALT ratio ≥2: Strongly suggests alcoholic liver disease 5, 6
- AST/ALT ratio ≥1: High specificity for cirrhosis in chronic HCV 1
- AST/ALT ratio <1: Common in non-alcoholic fatty liver disease (NAFLD) 1, 5
- AST/ALT ratio >1: Indicates advanced fibrosis/cirrhosis even when both values are within normal range 4
3. Monitoring Disease Progression
- Regular monitoring helps assess:
- Response to treatment
- Disease progression
- Development of complications
- Risk of fibrosis and cirrhosis
Interpretation of Elevated Levels
Severity Classification
- Mild elevation: <5× upper limit of normal (ULN)
- Moderate elevation: 5-10× ULN
- Severe elevation: >10× ULN 1
Common Causes of Elevation
- Non-alcoholic fatty liver disease (NAFLD): Most common cause in patients with metabolic syndrome
- Alcoholic liver disease: Typically presents with AST/ALT ratio ≥2
- Viral hepatitis: Including hepatitis B and C
- Drug-induced liver injury: Can cause significant elevations
- Autoimmune hepatitis: Often presents with persistent elevations
- Cirrhosis: Advanced liver disease regardless of etiology
Clinical Applications
Initial Testing Recommendations
- Initial investigation for potential liver disease should include bilirubin, albumin, ALT, ALP, and GGT, along with a full blood count 4
- While routine testing of both AST and ALT together is not always necessary, subsequent testing to calculate the AST/ALT ratio is valuable for assessing fibrosis risk 4
When to Check Liver Enzymes
- Non-specific symptoms (fatigue, nausea, anorexia)
- Evidence of chronic liver disease (ascites, peripheral edema, spider naevi)
- High-risk conditions for liver disease
- Monitoring patients on potentially hepatotoxic medications 4
Management Based on Results
- Mild elevations: Repeat testing within 1-2 weeks
- Moderate to severe elevations: Repeat within 2-5 days
- Persistent elevations: Further evaluation with imaging and possibly liver biopsy
Pitfalls and Caveats
- AST is less specific than ALT for liver damage due to its presence in other tissues
- Both AST and ALT can be normal even in the setting of cirrhosis 4
- The AST/ALT ratio remains useful even when both values are within normal range
- Isolated elevations should be interpreted in clinical context and with other liver tests
- In patients with abnormal baseline liver tests, the upper limit of normal should be adjusted to the mean baseline values 4
When to Refer to Hepatology
- Persistent elevation >6 months despite interventions
- Signs of hepatic decompensation
- Suspected autoimmune hepatitis
- ALT elevation >5× ULN 1
By understanding and properly interpreting AST and ALT levels, clinicians can effectively diagnose liver diseases, assess their severity, monitor disease progression, and guide appropriate management strategies.