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Liver Function Tests (LFTs)
Liver function tests (LFTs) are a panel of biochemical tests used to assess hepatic integrity, metabolism, and synthetic function. No single test reflects all liver functions; they are used as a battery to detect and classify liver disease.
1. Serum Bilirubin
Normal total bilirubin: 0.2-0.9 mg/dL (upper limit ~1.5 mg/dL); conjugated fraction normally <0.3 mg/dL.
Bilirubin exists in two fractions:
| Fraction | Also Called | Solubility | Significance |
|---|
| Unconjugated | Indirect | Water-insoluble (albumin-bound) | Elevated in hemolysis, Gilbert's, Crigler-Najjar |
| Conjugated | Direct | Water-soluble | Elevated in liver/biliary tract disease |
- The rate-limiting step of bilirubin metabolism is transport of conjugated bilirubin into the bile canaliculi, not conjugation itself
- Conjugated hyperbilirubinemia almost always implies hepatic or biliary disease
- Bilirubinuria (bilirubin in urine) = always conjugated bilirubin = confirms hepatic/obstructive disease
- In most liver diseases, both fractions rise together
- Bilirubin is an important component of the MELD score (Model for End-Stage Liver Disease) for liver transplant prioritization
(Harrison's Principles of Internal Medicine 22E, p. 2677)
2. Serum Aminotransferases (Transaminases)
Tests: AST (aspartate aminotransferase) and ALT (alanine aminotransferase). Normal: 10-40 IU/L.
- ALT is found primarily in the liver - more specific for liver injury
- AST is present in liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas (less specific)
- These enzymes are released into blood when liver cell membrane permeability increases (necrosis is NOT required)
- Poor correlation between enzyme level and degree of liver damage - absolute elevation has no prognostic significance in acute disorders
Interpretation by level:
- Up to 300 IU/L: nonspecific, seen in any liver disorder
-
1000 IU/L: seen almost exclusively in viral hepatitis, ischemic liver injury, or toxin/drug-induced liver injury
AST:ALT ratio:
- ALT ≥ AST: most acute hepatocellular disorders
- AST:ALT ratio >2:1 (especially >3:1): strongly suggests alcoholic liver disease
- AST:ALT >1 may also be seen in cirrhosis of any cause
(Harrison's Principles of Internal Medicine 22E, p. 2678)
3. Serum Alkaline Phosphatase (ALP)
Normal: 30-120 IU/L (varies by lab).
ALP exists in multiple isoforms - liver, bone, intestine, placenta. In liver disease, ALP is derived from the bile duct epithelium and is induced by bile acids.
- Elevated in cholestasis (intra- or extra-hepatic), bile duct injury, and space-occupying lesions of the liver
- Mild elevation (<3x normal): many liver and non-liver conditions
- Marked elevation (>4x normal): strongly suggests cholestasis or infiltrative disease
- To confirm hepatic origin: measure GGT or 5'-nucleotidase (both hepatic-specific; bone disease elevates ALP but NOT GGT)
Pattern: Predominant ALP + GGT elevation with lesser aminotransferase rise = cholestatic pattern
4. Gamma-Glutamyl Transpeptidase (GGT)
- A microsomal enzyme elevated in cholestatic disease
- Induced by alcohol and drugs (phenytoin, barbiturates) - useful marker of alcohol abuse
- Not elevated in bone disease (unlike ALP) - helps confirm hepatic origin of ALP elevation
- Very sensitive but not specific for liver disease
5. Serum Albumin
Normal: 3.5-5.0 g/dL; half-life ~20 days.
- Synthesized exclusively by the liver
- Reflects hepatic synthetic function
- Low albumin indicates chronic liver disease (cirrhosis, chronic hepatitis)
- Not useful in acute liver disease due to the long half-life (serum levels take weeks to fall)
- Non-hepatic causes of hypoalbuminemia: malnutrition, nephrotic syndrome, protein-losing enteropathy
6. Prothrombin Time (PT) / INR
- Coagulation factors I, II, V, VII, IX, X are synthesized by the liver; factor VII has the shortest half-life (~6 hours)
- A prolonged PT/elevated INR indicates impaired hepatic synthetic function
- Most sensitive marker of acute liver synthetic failure (responds within hours, unlike albumin)
- Used in Child-Pugh score and MELD score for prognosis
- PT that does not correct with Vitamin K administration indicates severe hepatocellular failure (vs. simply Vitamin K deficiency)
Pattern Recognition Summary
| Pattern | Predominant Abnormality | Likely Diagnosis |
|---|
| Hepatocellular | ALT/AST elevated (>>ALP) | Viral hepatitis, NASH, ischemia |
| Cholestatic | ALP/GGT elevated (>>ALT) | Obstruction, PBC, PSC |
| Alcoholic | AST:ALT >2:1, elevated GGT | Alcoholic liver disease |
| Synthetic failure | Low albumin, prolonged PT | Cirrhosis, fulminant hepatic failure |
| Fulminant failure | All markedly elevated + hyperammonemia | Acute liver failure |
(Harrison's Principles of Internal Medicine 22E, p. 2677-2678; Tietz Textbook of Laboratory Medicine 7th Ed; Henry's Clinical Diagnosis, p. 3821-3834)