What are the causes of aspartate transaminase (AST) being greater than alanine transaminase (ALT)?

Causes of AST Greater Than ALT

The most common causes of AST being greater than ALT include alcoholic liver disease, muscle injury, cirrhosis, and certain specific conditions like Wilson disease. 1

Primary Causes of AST > ALT

1. Alcoholic Liver Disease

• AST:ALT ratio typically >2:1 in alcoholic hepatitis 2
• This ratio is a key diagnostic feature that helps distinguish alcoholic liver disease from other liver conditions
• The higher ratio occurs because alcohol affects mitochondria, where AST is concentrated

2. Muscle Disorders/Injury

• AST is present in cardiac and skeletal muscle as well as liver, while ALT is more liver-specific 1
• Causes include:
  • Extreme exercise
  • Polymyositis
  • Seizures
  • Myopathies
  • Rhabdomyolysis
• In acute muscle injury, AST/ALT ratio is typically >3, but approaches 1 after a few days due to faster decline in AST 3

3. Cirrhosis (Any Etiology)

• As chronic liver disease progresses to cirrhosis, the AST/ALT ratio often rises to >1 4
• In a study of 100 patients with chronic hepatitis B:
  • Mean AST/ALT ratio was 0.59 in those without cirrhosis
  • Mean AST/ALT ratio was 1.02 in those with cirrhosis
• This ratio increase occurs regardless of the underlying cause of cirrhosis

4. Specific Metabolic Conditions

• Wilson disease: AST often higher than ALT, reflecting mitochondrial damage 5
• Glycogen Storage Disease Type III: AST usually higher than ALT 1

5. Other Causes

• Hemolysis (AST present in red blood cells)
• Thyroid disease
• Cardiac injury (myocardial infarction)
• Advanced liver disease of any etiology

Diagnostic Approach

When encountering AST > ALT, consider this algorithm:

1. Check AST:ALT ratio:

   • Ratio >2: Strongly suggests alcoholic liver disease 2
   • Ratio 1-2: Consider cirrhosis, Wilson disease, or muscle disorders
   • Ratio just slightly >1: May be normal variant or early disease

2. Evaluate for muscle injury:

   • Check creatine kinase (CK) levels
   • Review history for exercise, seizures, trauma, or myopathy
   • If CK elevated, muscle source is likely

3. Assess for alcoholic liver disease:

   • Detailed alcohol history
   • Look for other markers: elevated GGT, macrocytosis

4. Consider cirrhosis:

   • Check for clinical signs of cirrhosis
   • Evaluate synthetic function (albumin, prothrombin time)
   • Consider imaging or other non-invasive fibrosis markers

5. Rule out Wilson disease if patient is young:

   • Check ceruloplasmin, 24-hour urinary copper
   • Look for Kayser-Fleischer rings
   • Note that low alkaline phosphatase is characteristic

Clinical Significance

AST elevation appears to be a stronger predictor of mortality than ALT elevation:

• Patients with elevated AST (≥40 IU/L) had life expectancy reduced by 10.2 years
• This was double the reduction seen with elevated ALT (5.2 years) 6
• AST was a better predictor for both all-cause and liver-related mortality

Common Pitfalls

1. Misattributing AST elevation to liver disease when it's from muscle

   • Always consider checking CK when AST is disproportionately elevated

2. Overlooking cirrhosis in non-alcoholic liver disease

   • Remember that as non-alcoholic liver disease progresses to cirrhosis, the AST/ALT ratio often rises above 1 4

3. Focusing only on ratio without considering absolute values

   • Very high absolute values of both enzymes may indicate acute hepatitis regardless of ratio

4. Failing to recognize Wilson disease

   • In acute liver failure due to Wilson disease, AST > ALT with low alkaline phosphatase is characteristic 5

By systematically evaluating the pattern of liver enzyme elevation and considering these common causes, the source of AST predominance can usually be identified and appropriate management initiated.