What does it mean when Alanine Transaminase (ALT) is elevated and Aspartate Transaminase (AST) is normal?

Elevated ALT with Normal AST: Clinical Significance

An isolated elevation of ALT with normal AST is highly specific for hepatocellular liver injury, as ALT is primarily concentrated in liver tissue with minimal presence in cardiac muscle, skeletal muscle, or red blood cells, making it the most liver-specific aminotransferase available. 1, 2

Why ALT is More Specific Than AST

• ALT has superior hepatic specificity because it exists in low concentrations in skeletal muscle and kidney, whereas AST is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells 1, 3
• Normal ALT levels are 29-33 IU/L in men and 19-25 IU/L in women, and elevations strongly correlate with hepatocellular injury 1, 2
• When AST remains normal but ALT is elevated, this pattern excludes significant cardiac injury, skeletal muscle damage, and hemolysis as contributing factors 3, 4

Most Common Causes of Isolated ALT Elevation

The hepatocellular pattern with predominant ALT elevation (AST/ALT ratio <1) is most characteristic of:

• Non-alcoholic fatty liver disease (NAFLD) - the most common cause in patients with metabolic risk factors including obesity, diabetes, and hypertension 2
• Viral hepatitis (acute or chronic hepatitis B, C, or E) - particularly when ALT exceeds 3× upper limit of normal 2
• Medication-induced liver injury - from prescription medications, over-the-counter drugs, or herbal supplements 2
• Early stages of other hepatobiliary disorders before AST becomes involved 1

Clinical Significance of the AST/ALT Pattern

• An AST/ALT ratio <1 essentially rules out alcoholic liver disease, which typically presents with AST/ALT ratio >2 2, 5
• The isolated ALT elevation indicates hepatocellular injury rather than cholestatic disease (which would elevate alkaline phosphatase) 1
• Normal AST with elevated ALT suggests the liver injury is in earlier stages, as AST tends to rise later in disease progression 5

Recommended Diagnostic Approach

Initial evaluation should include:

• Complete liver panel (ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin, albumin, prothrombin time/INR) to assess for cholestatic patterns and synthetic function 2
• Viral hepatitis serologies (HBsAg, anti-HBc, anti-HCV) 2
• Detailed alcohol consumption history and complete medication review including supplements 2
• Assessment for metabolic syndrome components (obesity, diabetes, hypertension, dyslipidemia) 2

Imaging evaluation:

• Abdominal ultrasound is the first-line imaging test, with 84.8% sensitivity and 93.6% specificity for detecting moderate to severe hepatic steatosis 2

Severity Classification and Management

Classify ALT elevation as:

• Mild: <5× upper limit of normal 1, 6
• Moderate: 5-10× upper limit of normal 1, 6
• Severe: >10× upper limit of normal 1, 6

Management based on severity:

• For mild elevations without identified cause, repeat liver enzymes in 2-4 weeks 2
• For ALT >5× ULN or bilirubin >2× ULN, urgent hepatology referral is warranted 2
• Consider hepatology referral if transaminases remain elevated for ≥6 months or if there is evidence of synthetic dysfunction 2

Important Pitfalls to Avoid

• Do not assume isolated ALT elevation is benign - ALT elevation ≥5× ULN is rare in NAFLD alone and requires investigation for viral hepatitis, autoimmune hepatitis, or drug-induced liver injury 2
• Do not overlook non-hepatic causes - recent intensive exercise can transiently elevate ALT, so check creatine kinase if muscle injury is suspected 2, 4
• Do not delay evaluation - normal AST does not exclude significant liver disease, and up to 10% of patients with advanced fibrosis may have normal or near-normal transaminases 2
• Women have lower normal ALT ranges than men, making elevations potentially more significant in female patients 2