1. Significance of Liver Function Tests
By: Hildegarde Y. Vistal MD
FPCP, FPSG, FPSDE

2. The liver performs a diverse array of biochemical, synthetic and excretory functions and as a result, no single biochemical test is capable of providing an accurate global assessment of hepatic function.

3. Tests are needed to: Detect disease Direct the diagnostic work-up
Determine severity
Assess prognosis
Evaluate therapy

4. Classifications of the Liver function tests
Markers of Hepatocellular necrosis
Aminotransferases
ALT (Alanine Transaminase or SGPT)
AST (Aspartate Transaminase or SGOT)
LDH (Lactate Dehydrogenase)
Makers of Cholestasis
GGTP (Gamma Glutamyl Transpeptidase)
Alkaline Phosphatase
Bilirubin
Markers of Hepatic Synthetic Capacity
Prothrombin Time
Albumin

5. Markers of Hepatocellular necrosis
Aminotransferases
ALT (Alanine Transaminase or SGPT)
- a cytosolic enzyme, that is liver specific
- elevation is a result of leakage from damaged cells, reflecting hepatic injury
AST (Aspartate Transaminase or SGOT)
- present in both cytosolic and mitochondrial isoenzymes
- also found in skeletal, cardiac muscle, kidney, brain, pancreas, and blood cells,
-seen in hepatocytes
*AST/ ALT Ratio
- useful in differential diagnosis
- ratio < or = to 1  acute liver injury
- ratio > than 2 – alcholic hepatitis
*Modest elevations
- levels < 500 U/L
*Marked elevations
- levels > 500 U/L

6. Algorithm for managing a patient with an isolated increase in serum aminotransferase

7. Markers of Hepatocellular necrosis
LDH (Lactate Dehydrogenase)
- seen with skeletal and cardiac muscle injury, hemolysis, stroke and renal infarction
- acute and chronic liver disease
- very non-specific

8. Makers of Cholestasis GGTP (Gamma Glutamyl Transpeptidase)
-derived from hepatocytes and biliary epithlia
- found also in the kidneys, spleen, pancreas, heart, lung, and brain.
- is a microsomal enzyme inducible by alcohol and drugs (anticonvulsants and warfarin)

9. Makers of Cholestasis Alkaline Phosphatase
- present in a variety of tissues including liver, bone, intestine, kidney, placenta, leucocytes ( various neoplasms)
- major sources are bone and liver
* Levels up to 3 times normal are relatively non-specific
* Striking elevations are seen with infiltrative hepatic disorders ( primary or metastatic tumors, intra or extra hepatic biliary obstruction)

10. Algorithm for managing a patient in an isolated increase in a serum Alkaline Phophatase

11. Makers of Cholestasis Bilirubin
- organic anion derived from the catabolism of hemoglobin
- production is accelerated by hemolysis, ineffective erythoropoeisis
1. Unconjugated Hyperbilirubinemia
-indirect bilirubin, lipid soluble ( 85%)
- results from increased bilirubin production or inherited or acquired defects in hepatic uptake or conjugation
- seen in hemolysis
2. Conjugated Hyperbilirubinemia
- direct bilirubin water soluble ( > 50%)
- results of inherited or acquired defects in hepatic excretion
- useful prognostically in patients with alcholic hepatitis, primary biliary cirrhosis, or accute liver failure

12. Algorithm for managing a patient with an isolated increase in serum total bilirubin.

13. Markers of Hepatic Synthetic Capacity
Prothrombin Time
- Liver plays a crucial role in hemostasis
Differential Diagnosis
Elevated PT
1. Vitamin K deficiency
- malnutrtion
- malabsortion
- antibiotic use
2. Warfarin administration
3. DIC ( Factor VIII)
4. Liver Disease ( Normal or increase factor VIII)
Prolongation of PT
1. Decompensated liver disease ( with hepatocellular dysfunction)
2. Chronic cholestatic disease

14. Markers of Hepatic Synthetic Capacity
Albumin
- 10 grams of albumin is synthesis and secreated by hepatocytes each day
Factors that affect albumin levels
1. Nutritional and volume status
2. Vascular integrity
3. Catabolism
4. Hormonal Factors
5. Kidney disease
6. Liver disease
- serum albumin level correlates with prognosis in chronic liver disease

15. Associated Liver Diseases
Test (Normal Range)
Basis of Abnormality
Associated Liver Diseases
Extrahepatic Source
Aminotransferases
(10-55 U/L, ukat/L for ALT, U/L, ukat/L for AST)
Leakage from damaged tissue
Modest elevation- many types of liver disease
Marked elevations- hepatitis (viral, autoimmune, toxic, and ischemic)
AST/ALT > 2 with the value of each less than 300 U suggests alcoholic liver diseases or cirrhosis of any etiology
ALT, relatively specific for hepatocyte necrosis
AST, muscle (skeletal and cardiac), kidney, brain, pancreas, red blood cells
Alkaline phosphate
( U/L, ukat/L)
Overproduction and leakage into serum
Modest elevations-many types of liver disease
Marked Elevations- extra- and intrahe- patic cholestasis, diffuse infiltrating disease (e.g., tumor, MAC), occasionally alcoholic hepatitis
Bone Growth or disease (e.g. tumor, fracture, Paget’s disease), placenta, intestine, tumors
Gammaglutamyl transpeptidase
(0-30 U/L, ukat/L)
?Overproduction and leakage into serum
Same as for alkaline phosphate; induced by ethanol, drugs
GGTP/AP > 2.5 suggests (but not diagnostic of) alcoholic liver disease
Kidney, spleen, pancreas, heart, lung, brain
5’-Nucleotidase
(0-11 U/L, ukat/L)
Same as for alkaline phosphate
Found in many tissues but serum elevation relatively specific for liver disease
Bilirubin
( mg/dL, 0-17 umol/L)
Decreased hepatic clearance
Marked Elevations- extra- and intrahe- patic bile duct obstruction, alcoholic, drug-induced or viral hepatitis, inherited hyperbilirubinemia
Increased breakdown of hemoglobin (resulting from hemolysis, ineffective erythropoiesis, resorption of hematoma) or myoglobin (resulting from muscle injury)
Prothrombin time
( sec) or International Nromalized Ratio (INR) ( )
Decreased synthetic capacity
Acute or chronic layer liver failure (unresponsive to vitamin K)
Biliary obstruction (usually responsive to vitamin K administration)
Vitamin K deficiency (secondary to malabsorption, malnutrition, antibiotics), consumptive coagulopathy
Albumin
( g/dL, g/L
Decreased synthesis
?Increased catabolism
Chronic liver failure
Decreased in nephrotic syndrome, protein-losing enetrophaty, vascular leak, malnutrition, malignancy, aodinflamatory states.