What does an elevated Aspartate Aminotransferase (AST) with a normal Alanine Aminotransferase (ALT) indicate?

Elevated AST with Normal ALT: Diagnostic Approach

An isolated elevation of AST (SGOT) with normal ALT (SGPT) most commonly indicates a non-hepatic source of enzyme elevation, particularly from cardiac or skeletal muscle injury, rather than primary liver disease. 1, 2

Why AST Lacks Liver Specificity

AST is present in multiple tissues beyond the liver, making it a poor marker for isolated hepatocellular injury:

• AST is found in cardiac muscle, skeletal muscle, kidneys, and red blood cells, which explains why elevations can occur without liver involvement 1, 2
• ALT is highly specific for liver injury due to its predominant concentration in hepatocytes with minimal presence in other tissues 1
• When true hepatocellular injury exists, both ALT and AST typically rise together, with ALT usually being equal to or greater than AST (AST/ALT ratio <1) 3, 1

Primary Differential Diagnosis

Non-Hepatic Causes (Most Likely)

Muscle-related conditions should be your first consideration:

• Skeletal muscle injury from exercise, trauma, or myopathy 2, 4
• Cardiac injury including acute myocardial infarction or other cardiac muscle damage 2, 4
• Polymyositis or other inflammatory muscle disorders 4

Other non-hepatic causes:

• Hemolysis (AST released from red blood cells) 2
• Hypothyroidism can cause mild AST elevation 4

Hepatic Causes (Less Likely with Normal ALT)

Alcoholic liver disease is the main hepatic exception where AST may be disproportionately elevated:

• AST/ALT ratio >2 (and especially >3) is highly suggestive of alcoholic liver disease, even when both are elevated 3
• In approximately 70% of alcoholic hepatitis cases, the AST/ALT ratio exceeds 2 3
• However, if ALT is truly normal, alcoholic liver disease is unlikely to be the sole cause 3

Recommended Diagnostic Algorithm

Step 1: Confirm the Finding and Assess Severity

• Repeat AST and complete liver panel (ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, PT/INR) within 1-2 weeks 1
• Verify that ALT remains normal on repeat testing 1

Step 2: Evaluate for Muscle Source

Measure creatine kinase (CK) to rule out skeletal or cardiac muscle injury:

• Elevated CK confirms muscle origin of AST elevation 1
• Obtain detailed history of recent exercise, trauma, or muscle symptoms 1
• Consider cardiac evaluation (troponin, ECG) if cardiac injury is suspected 2, 4

Step 3: Assess for Other Non-Hepatic Causes

• Check thyroid function tests (TSH, free T4) to exclude hypothyroidism 1
• Review complete blood count for evidence of hemolysis 2
• Obtain detailed medication and supplement history 1

Step 4: Detailed Alcohol History

• Quantify alcohol consumption using validated screening tools (AUDIT questionnaire) 3
• An AUDIT score ≥8 or one or more heavy drinking days warrants further evaluation 3
• If significant alcohol use is present and AST/ALT ratio >2, alcoholic liver disease becomes more likely despite "normal" ALT 3

Step 5: Consider Imaging Only If Indicated

• Abdominal ultrasound is NOT routinely needed if muscle source is confirmed and ALT remains normal 1
• Consider ultrasound only if: GGT is also elevated, alkaline phosphatase is elevated, or clinical suspicion for structural liver disease exists 1

Critical Pitfalls to Avoid

Do not assume liver disease based on isolated AST elevation:

• AST alone is insufficient to diagnose or monitor liver disease without corresponding ALT elevation 1
• Many clinicians over-interpret isolated AST elevations as hepatic when the source is extrahepatic 2

Do not order extensive hepatic workup prematurely:

• Check CK first before pursuing viral hepatitis serologies, autoimmune panels, or liver imaging 1
• Unnecessary testing increases costs and patient anxiety when muscle injury is the likely cause 1

Recognize gender-specific reference ranges:

• Normal ALT ranges are 29-33 IU/L for males and 19-25 IU/L for females 1
• What appears "normal" by laboratory standards may actually represent mild elevation in women 1

When to Refer or Pursue Further Evaluation

Hepatology referral is indicated if:

• AST remains elevated >6 months without identified cause 1
• Evidence of synthetic dysfunction develops (low albumin, elevated INR, elevated bilirubin) 1
• AST increases to >5× upper limit of normal 1

Cardiology or rheumatology referral if:

• Elevated CK with cardiac symptoms suggests myocardial injury 2, 4
• Elevated CK with muscle weakness suggests inflammatory myopathy 4