Evaluating Elevated ALT versus AST
ALT is the most specific marker for hepatocellular liver injury because it is primarily concentrated in liver tissue with minimal presence in other organs, making ALT elevation more meaningful than AST for identifying liver damage. 1
Key Differences in Specificity
ALT (Alanine Aminotransferase)
- ALT exists in low concentrations in skeletal muscle and kidney, making it highly liver-specific compared to other aminotransferases 1
- Normal ALT ranges are sex-specific: 29-33 IU/L for males and 19-25 IU/L for females, significantly lower than commercial laboratory cutoffs 1
- ALT is the preferred marker for determining liver disease severity and is used in clinical trial eligibility criteria due to its superior hepatic specificity 1
AST (Aspartate Aminotransferase)
- AST is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making it significantly less liver-specific 1, 2
- AST can be elevated in non-hepatic conditions including:
Diagnostic Patterns Using AST/ALT Ratio
AST/ALT Ratio < 1 (ALT > AST)
- Characteristic of nonalcoholic fatty liver disease (NAFLD), viral hepatitis, or medication-induced liver injury 1
- This pattern indicates hepatocellular injury rather than cholestatic disease 1
AST/ALT Ratio ≥ 2
- Highly suggestive of alcoholic liver disease, with ratios >3 being particularly specific for this diagnosis 4, 5
- In alcoholic hepatitis, 70% of patients demonstrate an AST/ALT ratio >2, with mean AST around 152 U/L and ALT around 70 U/L 4
- An AST/ALT ratio >1.5 is seen in >98% of histologically proven alcoholic hepatitis cases 4
AST/ALT Ratio ≥ 1 in Non-Alcoholic Disease
- Strongly suggests cirrhosis and warrants evaluation for complications such as varices, ascites, and synthetic dysfunction 1
- In chronic hepatitis C, an AST/ALT ≥1 has 95.9% specificity for distinguishing cirrhotic from non-cirrhotic patients, though sensitivity is only 46.7% 6
Practical Evaluation Algorithm
Step 1: Determine Injury Pattern
- Calculate the R-value: (ALT ÷ ULN ALT) / (ALP ÷ ULN ALP) 1
- R ≥ 5 = hepatocellular injury
- R ≤ 2 = cholestatic injury
- 2 < R < 5 = mixed injury
Step 2: Assess Magnitude of Elevation
- Mild elevation: <5× upper limit of normal 1
- Moderate elevation: 5-10× upper limit of normal 1
- Severe elevation: >10× upper limit of normal 1
Step 3: Calculate AST/ALT Ratio
- If ratio ≥2: Obtain detailed alcohol history (>40 g/day for women, >50-60 g/day for men) 4
- If ratio <1: Consider NAFLD, viral hepatitis, or medication-induced injury 1
- If ratio ≥1 in non-alcoholic disease: Assess for cirrhosis and calculate FIB-4 score 1
Step 4: Rule Out Non-Hepatic Sources of AST Elevation
- Measure creatine kinase (CK) to exclude muscle injury, particularly if the patient has engaged in intensive exercise or has muscle symptoms 1
- Review cardiac history and consider troponin if acute coronary syndrome is suspected 3
- Assess for hemolysis with complete blood count and peripheral smear if indicated 1
Common Pitfalls to Avoid
- Do not assume AST elevation is liver-specific without checking CK; intensive exercise, muscle injury, and cardiac injury can all elevate AST more than ALT 1
- Do not overlook the AST/ALT ratio in suspected alcoholic liver disease; a ratio >1.5 is seen in >98% of histologically proven cases 4
- Do not use commercial laboratory "normal" ranges for ALT; sex-specific thresholds (29-33 IU/L for men, 19-25 IU/L for women) are more accurate 1
- Do not assume normal ALT excludes significant liver disease; up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds 1