AST: The Systemic Sentinel
Aspartate aminotransferase (AST), historically known as SGOT, serves as a critical biomarker in clinical medicine. While often grouped with ALT, AST is less liver-specific and more broadly distributed throughout the body. It is found in significant concentrations in the myocardium (heart muscle), skeletal muscle, kidneys, brain, and erythrocytes (red blood cells).
An elevation does not automatically imply liver disease; rather, it signals tissue injury that requires contextual interpretation. AST’s unique biochemistry provides nuanced diagnostic data that can reveal the etiology and severity of disease.
Understanding AST requires analyzing its dual nature and kinetic profile.
Visualizing cAST (floating) vs mAST (sequestered)
Cytosolic (cAST): Accounts for approximately 20% of activity. It is released easily in response to mild, reversible cell membrane injury (e.g., early viral hepatitis).
Mitochondrial (mAST): Accounts for 80% of activity. Sequestered deep within mitochondria; its release requires severe necrosis or direct mitochondrial toxins like alcohol.
AST catalyzes the transfer of amino groups, requiring Vitamin B6 as a cofactor.
Half-life: Approximately 17 ± 5 hours. This is significantly shorter than ALT (~47 hours), which explains why AST levels normalize faster than ALT during the resolution of acute injury.
Unlike the liver-centric ALT, AST is abundant in:
- Myocardium (Heart)
- Skeletal Muscle
- Erythrocytes (Red Blood Cells)
- Kidneys & Brain
Narrowing the Differential
Derived by Fernando De Ritis, the AST/ALT ratio is a powerful heuristic for determining etiology.
Pattern Shift: Alcohol (AST dominant) vs Viral (ALT dominant)
| Ratio Pattern | Clinical Significance | Mechanism |
|---|---|---|
| AST/ALT > 2:1 | Alcohol-Associated Liver Disease | Alcohol is a mitochondrial toxin releasing mAST. Vitamin B6 deficiency suppresses ALT synthesis more than AST. |
| AST/ALT < 1 | Viral Hepatitis / MASLD | Cytosolic release predominates; longer half-life of ALT leads to accumulation. |
| Ratio Reversal (>1) | Cirrhosis Progression | Predicts advanced fibrosis due to impaired sinusoidal clearance. |
| AST/ALT > 4 | Wilson’s Disease | Massive copper release causes mitochondrial damage + Hemolysis (RBC AST release). |
⚠️ False Positives & Pre-Analytical Errors
Because AST is abundant in red blood cells (15–40x serum concentration), results are highly prone to interference.
Hemolysis releasing "sub-visual" AST spikes
- Hemolysis: Even invisible ("sub-visual") hemolysis can elevate AST, potentially misclassifying healthy patients. AST is far more sensitive to this than ALT.
- Macro-AST: A benign condition where AST complexes with Immunoglobulins (IgG or IgA). The large complex cannot be cleared by kidneys, leading to persistent elevation.
- Exertional Rhabdomyolysis: Strenuous physical activity can elevate AST 3–5 times the ULN for up to 7 days.
AST is a core component of non-invasive fibrosis scoring systems used to stage liver disease without a biopsy.
APRI (AST to Platelet Ratio Index)
Uses the principle that as liver disease progresses, AST rises (reduced clearance) and platelets fall (splenic sequestration).
FIB-4 Score
Combines Age, AST, ALT, and Platelets. It is the primary screening tool recommended to identify patients with advanced fibrosis (F3-F4) in MASLD and Hepatitis C.
Clinical Takeaway: The Contextual Context
While ALT is the gold standard for liver injury, AST tells the rest of the story. A high AST demands a specific line of questioning:
- Is it the liver? Check ALT, GGT, Bilirubin.
- Is it muscle? Check Creatine Kinase (CK).
- Is it blood? Check for Hemolysis.
- Is it alcohol? Check the De Ritis Ratio.
Pearl: In ischemic "shock liver," AST peaks first and falls rapidly. A slow decline suggests ongoing viral or toxic injury.