What does an aspartate transaminase (AST) level double the normal range with a normal alanine transaminase (ALT) level indicate?

AST Double the Normal with Normal ALT: Clinical Significance

An AST level that is double the normal range with a normal ALT most commonly indicates a non-hepatic source of AST elevation, particularly from cardiac muscle, skeletal muscle, or red blood cells, rather than primary liver disease. 1, 2

Understanding AST Specificity

AST is significantly less liver-specific than ALT because it is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making it essential to determine whether the elevation originates from hepatic or non-hepatic sources. 1, 3 In contrast, ALT is highly specific for liver injury due to its low concentrations in skeletal muscle and kidney, with normal ranges of 29-33 IU/L for males and 19-25 IU/L for females. 1, 2

Most Likely Causes

Non-Hepatic Sources (Most Common)

• Cardiac injury or myocardial infarction can cause isolated AST elevation without ALT elevation, as AST is abundant in cardiac muscle. 3, 4
• Skeletal muscle injury from recent intensive exercise, weight lifting, or muscle disorders (polymyositis, muscular dystrophy) commonly elevates AST disproportionately to ALT. 1, 4
• Hemolysis from red blood cell breakdown releases AST without affecting ALT levels. 1, 4

Hepatic Causes (Less Likely with Normal ALT)

• Alcoholic liver disease typically shows an AST/ALT ratio >2, but both enzymes are usually elevated above normal, not just AST. 2, 5
• Cirrhosis from any cause can produce an AST/ALT ratio ≥1, but again, both values are typically elevated. 1, 6

Diagnostic Algorithm

Immediate Assessment

• Obtain a detailed history focusing on recent chest pain or cardiac symptoms, recent intensive exercise or muscle trauma, and current medications that may cause muscle injury (statins, fibrates). 1, 2, 4
• Measure creatine kinase (CK) to rule out muscle injury as the source of AST elevation, as elevated CK confirms a muscular origin. 1, 2
• Obtain troponin levels if cardiac injury is suspected based on symptoms or risk factors. 3, 4
• Check thyroid function tests (TSH) as hypothyroidism can cause both muscle injury and elevated AST. 1, 4

If Initial Tests Are Unrevealing

• Complete liver panel including alkaline phosphatase, GGT, total and direct bilirubin, albumin, and prothrombin time to assess for cholestatic patterns and synthetic function. 1, 2
• Viral hepatitis serologies (HBsAg, HBcIgM, HCV antibody) if any risk factors are present. 1, 2
• Abdominal ultrasound as first-line imaging if liver disease is still suspected despite normal ALT, with sensitivity of 84.8% and specificity of 93.6% for detecting moderate to severe hepatic steatosis. 1, 2

Critical Pitfalls to Avoid

• Do not assume liver disease based on isolated AST elevation without confirming with ALT elevation or other liver-specific markers, as AST elevation alone is more likely from non-hepatic sources. 1, 3
• Do not overlook recent exercise as a cause, as intensive physical activity can cause acute AST elevations that may be mistaken for liver injury. 1, 4
• Do not miss cardiac injury, particularly in older patients or those with cardiovascular risk factors, as myocardial infarction can present with isolated AST elevation. 3, 4

When to Refer

• If AST remains elevated after excluding non-hepatic causes and repeat testing in 2-4 weeks shows persistent elevation. 1, 2
• If evidence of synthetic dysfunction develops (low albumin, elevated INR, elevated bilirubin). 1, 2
• If AST increases to >5× upper limit of normal (>165 IU/L for males, >125 IU/L for females) despite normal ALT. 1, 2