Causes of AST:ALT Elevation Ratio of 2:1
Alcohol-induced liver disease is the most common cause of an AST:ALT ratio ≥2:1, which is highly suggestive of alcoholic liver disease. 1
Primary Causes of AST:ALT Ratio ≥2:1
Alcoholic Liver Disease
- The AST:ALT ratio is generally >2 in alcohol-induced fatty liver disease, making it a key diagnostic marker 1
- In about 70% of patients with alcoholic liver disease, the AST/ALT ratio is higher than 2 1
- Ratios greater than 3 are highly suggestive of alcoholic liver disease 1
- This elevated ratio in alcoholic liver disease contrasts with the ratio of <1 typically seen in metabolic disease-related fatty liver 1
Advanced Liver Disease/Cirrhosis
- As liver disease progresses to cirrhosis, the AST:ALT ratio often increases above 1.0, even in non-alcoholic liver disease 2
- In patients with cirrhosis due to alcohol, 69% had a ratio ≥2, compared to only 8% with a ratio ≤1.0 3
- The AST:ALT ratio may reverse (become >1) when cirrhosis first becomes manifest in chronic viral hepatitis 2
- In NASH (Non-Alcoholic Steatohepatitis), the ratio increases with progression of fibrosis - mean ratios of 0.7,0.9, and 1.4 for no fibrosis, mild fibrosis, and cirrhosis, respectively 4
Mechanism Behind Elevated AST:ALT Ratio
- AST is present in multiple tissues (liver, cardiac and skeletal muscle, erythrocytes), while ALT is more liver-specific 5
- In alcoholic liver disease, alcohol causes mitochondrial damage, leading to greater release of AST (which is found in both mitochondria and cytosol) compared to ALT (found primarily in cytosol) 1
- Advanced liver disease leads to reduced clearance of AST relative to ALT, contributing to the elevated ratio 3
Other Potential Causes of Elevated AST
- Non-hepatic causes of predominantly elevated AST include:
- Hemolysis
- Myopathy
- Thyroid disease
- Exercise
- Cardiac injury 1
- Macro-AST (a benign condition where AST binds to immunoglobulins) can cause isolated AST elevation 6
Clinical Pearls and Pitfalls
Pearls
- An AST:ALT ratio >2 is strongly suggestive of alcoholic liver disease, while values <1 suggest NAFLD/NASH 4
- The AST:ALT ratio should be interpreted in context of other clinical findings, as it may be less helpful in distinguishing alcoholic from non-alcoholic liver disease in the presence of cirrhosis 2
- Serum AST is typically elevated to 2-6 times the upper limits of normal in severe alcoholic hepatitis 1
Pitfalls
- AST levels >500 IU/L or ALT >200 IU/L are uncommon in alcoholic hepatitis and should prompt consideration of other etiologies 1
- Most patients with high alcohol consumption but without severe liver disease do not have an AST:ALT ratio above 1, so the ratio may indicate advanced disease rather than just heavy drinking 3
- Relying solely on AST:ALT ratio for diagnosis without considering other clinical and laboratory findings may lead to misdiagnosis 1