What is Aspartate Aminotransferase (AST)?
AST is an enzyme present in multiple organs including liver, heart, skeletal muscle, kidneys, and red blood cells, making it less specific for liver injury compared to ALT, which is predominantly found in hepatocytes. 1, 2
Biochemical Properties and Location
AST exists as two distinct isoenzymes in human tissues: cytoplasmic AST (c-AST or AST1) and mitochondrial AST (m-AST or AST2), both of which are homodimers containing pyridoxal phosphate as a prosthetic group. 3, 4
The enzyme catalyzes reversible transamination reactions and is located in striated muscle, myocardium, liver, kidneys, and erythrocytes, with both isoforms usually occurring together and interacting metabolically. 3, 4
AST plays a crucial role in supplying L-aspartate as a substrate for the urea cycle, purine and pyrimidine nucleotide synthesis in the liver, L-arginine synthesis in the kidney, and the purine nucleotide cycle in brain and skeletal muscle. 4
Clinical Significance and Diagnostic Limitations
AST is less specific for liver injury than ALT because it can be elevated in cardiac muscle disorders, skeletal muscle injury from extensive exercise, kidney disorders, and red blood cell disorders. 1, 2
In alcoholic liver disease, AST levels are typically elevated with an AST/ALT ratio greater than 1, and AST levels rarely exceed 300 IU/L in most forms of alcoholic liver disease. 5
Normal AST ranges differ by sex, though specific reference ranges are less well-defined than for ALT (which is 29-33 IU/L for males and 19-25 IU/L for females). 1
Macro-AST: An Important Pitfall
AST can form a complex with immunoglobulin, creating a macroenzyme (macro-AST) that causes persistent elevation in serum AST activity without indicating actual tissue damage. 6
Macro-AST can be detected by exclusion chromatography, electrophoresis, and activation assays with pyridoxal 5-phosphate, and these elevated values can persist for many years without clinical significance. 6
In pediatric patients with prolonged isolated AST elevation, approximately 22% are macro-AST positive and 44% have borderline levels, with a benign long-term course and no development of significant liver disease. 7
Diagnostic Approach When AST is Elevated
When AST is elevated in isolation without ALT elevation, liver and muscle disease can be biochemically excluded by checking serum alanine aminotransferase and creatine kinase levels. 6
Creatine kinase should be measured to rule out muscle disorders as a cause of AST elevation, particularly when both AST and ALT are elevated but the pattern suggests non-hepatic origin. 1
In patients with suspected muscular dystrophy, particularly Duchenne muscular dystrophy, creatine kinase levels should be checked to differentiate muscle from liver origin of AST elevation. 1
AST in Specific Clinical Contexts
In hepatitis C and other chronic liver diseases, AST is used in combination with platelet count to calculate the AST to platelet ratio index (APRI), though this has limited sensitivity (13.2%) for significant fibrosis in alcoholic liver disease. 5
In immune checkpoint inhibitor-induced liver injury, AST elevations above 1x to less than 3x upper limit of normal without bilirubin elevation are often non-specific and may be related to causes such as nonalcoholic fatty liver disease, dietary changes, or vigorous exercise. 5
In COVID-19 patients treated with remdesivir, mild-to-moderate AST elevation to 3-4 times upper limit of normal can occur as a medication effect. 5