What is the cause of elevated AST (Aspartate Aminotransferase) in a patient with normal alkaline phosphatase and ALT (Alanine Aminotransferase) levels?

Elevated AST with Normal Alkaline Phosphatase and ALT

The isolated elevation of AST (121 U/L) with normal ALT and alkaline phosphatase most likely indicates a non-hepatic source of AST elevation, particularly from cardiac muscle, skeletal muscle, kidney, or red blood cells, rather than primary liver disease. 1

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
• ALT is highly specific for liver injury as it is primarily concentrated in the liver with minimal presence in other tissues, and unlike AST, ALT elevations are specific indicators of liver damage due to low concentrations in skeletal muscle and kidney 1
• The normal ALT (31 U/L) and normal alkaline phosphatase (78 U/L) in this case strongly argue against primary hepatocellular injury or cholestatic liver disease 1

Most Likely Causes to Investigate

Muscle-Related Causes (Most Common)

• Measure creatine kinase (CK) immediately to rule out muscle disorders as the primary cause of AST elevation, as recent excessive exercise, muscle injury, or myopathic conditions can significantly elevate AST while sparing ALT 1
• Intensive exercise or weight lifting can cause acute AST elevations that may be mistaken for liver injury, particularly if the patient has engaged in vigorous physical activity recently 1
• Polymyositis and other muscle diseases can present with isolated AST elevation 2

Cardiac Causes

• Acute myocardial infarction or other cardiac muscle injury can elevate AST without affecting ALT 2
• Consider checking troponin levels if there are any cardiac symptoms or risk factors 2

Other Non-Hepatic Causes

• Hypothyroidism can cause elevated AST, so thyroid function tests (TSH, free T4) should be performed to rule out thyroid disorders 1, 2
• Hemolysis from red blood cell disorders can elevate AST 1
• Acute kidney injury should be assessed with serum creatinine and BUN 1

Diagnostic Algorithm

Immediate Testing (Within 2-3 Days)

• Creatine kinase (CK) - to identify muscle origin 1
• Troponin - if any cardiac symptoms or risk factors 2
• TSH and free T4 - to exclude thyroid disorders 1, 2
• Complete metabolic panel - to assess kidney function and exclude other causes 1
• Repeat AST, ALT, and alkaline phosphatase - to establish trend and confirm the pattern 1

If Initial Testing is Unrevealing

• Consider detailed alcohol consumption history, as an AST/ALT ratio >2 is highly suggestive of alcoholic liver disease, though the absolute ALT level here makes this less likely 1, 3
• Review all medications, including over-the-counter drugs and herbal supplements, for potential hepatotoxicity 1
• If AST remains elevated after excluding non-hepatic causes, proceed with complete liver panel including viral hepatitis serologies (HBsAg, anti-HCV), autoimmune markers, and metabolic parameters 1

When to Consider Liver Disease

• If the AST/ALT ratio is >1 in the context of chronic liver disease, this strongly suggests cirrhosis, with double the risk of liver-related death or transplantation 1
• However, with a normal ALT and normal alkaline phosphatase, primary liver disease is unlikely unless there is advanced cirrhosis with reversed AST/ALT ratio 4
• If liver disease is suspected despite normal ALT, calculate the FIB-4 score using age, ALT, AST, and platelet count to assess risk of advanced fibrosis 1

Critical Pitfalls to Avoid

• Do not assume isolated AST elevation represents liver disease without first excluding muscle, cardiac, and other non-hepatic sources 1, 2
• Do not overlook recent exercise history, as this is a common and benign cause of isolated AST elevation that resolves spontaneously 1
• Do not ignore the normal ALT - this is a critical clue that primary hepatocellular injury is unlikely 1, 3
• If both AST and ALT were elevated, consider checking CK to rule out muscle origin before attributing the elevation to liver disease 1

Monitoring Strategy

• If CK is elevated, repeat AST and CK after 1-2 weeks of rest from strenuous activity to confirm resolution 1
• If all non-hepatic causes are excluded and AST remains elevated, repeat liver enzymes in 2-4 weeks to establish a trend 1
• Consider hepatology referral only if AST remains elevated for ≥6 months without identified cause or if evidence of synthetic dysfunction develops 1