Significance of Liver Significance of Liver Function TestsFunction Tests

By: Hildegarde Y. Vistal MDBy: Hildegarde Y. Vistal MD

FPCP, FPSG, FPSDEFPCP, FPSG, FPSDE

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

Tests are needed to:Tests are needed to:

1.1. Detect diseaseDetect disease

2.2. Direct the diagnostic work-upDirect the diagnostic work-up

3.3. Determine severityDetermine severity

4.4. Assess prognosisAssess prognosis

5.5. Evaluate therapyEvaluate therapy

Classifications of the Liver function Classifications of the Liver function teststests

I.I. Markers of Hepatocellular necrosisMarkers of Hepatocellular necrosisA.A. Aminotransferases Aminotransferases

1.1. ALT (Alanine Transaminase or SGPT)ALT (Alanine Transaminase or SGPT)2.2. AST (AST (Aspartate Transaminase or SGOT)Aspartate Transaminase or SGOT)

B.B. LDH (Lactate Dehydrogenase)LDH (Lactate Dehydrogenase)

II.II. Makers of CholestasisMakers of CholestasisA.A. GGTP (Gamma Glutamyl Transpeptidase)GGTP (Gamma Glutamyl Transpeptidase)B.B. Alkaline PhosphataseAlkaline PhosphataseC.C. BilirubinBilirubin

III.III. Markers of Hepatic Synthetic CapacityMarkers of Hepatic Synthetic CapacityA.A. Prothrombin TimeProthrombin TimeB.B. AlbuminAlbumin

Markers of Hepatocellular necrosisMarkers of Hepatocellular necrosis

A.A. AminotransferasesAminotransferases1.1. ALT (Alanine Transaminase or SGPT)ALT (Alanine Transaminase or SGPT) - a cytosolic enzyme, that is liver specific- a cytosolic enzyme, that is liver specific

- elevation is a result of leakage from damaged cells, reflecting hepatic injury- elevation is a result of leakage from damaged cells, reflecting hepatic injury2.2. AST (AST (Aspartate Transaminase or SGOT)Aspartate Transaminase or SGOT)

- present in both cytosolic and mitochondrial isoenzymes- present in both cytosolic and mitochondrial isoenzymes- also found in skeletal, cardiac muscle, kidney, brain, pancreas, and blood cells,- also found in skeletal, cardiac muscle, kidney, brain, pancreas, and blood cells,-seen in hepatocytes-seen in hepatocytes

*AST/ ALT Ratio*AST/ ALT Ratio- useful in differential diagnosis- useful in differential diagnosis- ratio < or = to 1 - ratio < or = to 1 acute liver injury acute liver injury- ratio > than 2 – alcholic hepatitis- ratio > than 2 – alcholic hepatitis

*Modest elevations *Modest elevations - levels < 500 U/L- levels < 500 U/L

*Marked elevations*Marked elevations- levels > 500 U/L - levels > 500 U/L

Increased serumanimotransferase

AlcoholAbuse

ObesityDiabetes

Haemochromatosis

Chronichepatitis

Drughepatotoxicity

HeartFailure

Virus B and CMarkers

Algorithm for managing a patient with an Algorithm for managing a patient with an isolated increase in serum isolated increase in serum

aminotransferaseaminotransferase

Markers of Hepatocellular necrosisMarkers of Hepatocellular necrosis

B.B. LDH (Lactate Dehydrogenase)LDH (Lactate Dehydrogenase)- seen with skeletal and cardiac muscle - seen with skeletal and cardiac muscle injury, hemolysis, stroke and renal injury, hemolysis, stroke and renal infarctioninfarction

- acute and chronic liver disease- acute and chronic liver disease

- very non-specific- very non-specific

Makers of CholestasisMakers of Cholestasis

A.A. GGTP (Gamma Glutamyl GGTP (Gamma Glutamyl Transpeptidase)Transpeptidase)

-derived from hepatocytes and -derived from hepatocytes and biliary epithliabiliary epithlia

- found also in the kidneys, spleen, - found also in the kidneys, spleen, pancreas, heart, lung, and brain.pancreas, heart, lung, and brain.

- is a microsomal enzyme - is a microsomal enzyme inducible by alcohol and drugs inducible by alcohol and drugs (anticonvulsants and warfarin)(anticonvulsants and warfarin)

Makers of CholestasisMakers of Cholestasis

B.B. Alkaline PhosphataseAlkaline Phosphatase- present in a variety of tissues - present in a variety of tissues

including liver, bone, intestine, kidney, including liver, bone, intestine, kidney, placenta, leucocytes ( various placenta, leucocytes ( various neoplasms)neoplasms)

- major sources are bone and liver- major sources are bone and liver* Levels up to 3 times normal are relatively * Levels up to 3 times normal are relatively

non-specificnon-specific* Striking elevations are seen with infiltrative * Striking elevations are seen with infiltrative

hepatic disorders ( primary or metastatic hepatic disorders ( primary or metastatic tumors, intra or extra hepatic biliary tumors, intra or extra hepatic biliary obstruction)obstruction)

Increased serum alkaline phosphate

HighNormal

MitochondrialAntibodies

(PBC)

ERCP(sclerosing cholangitis)

MedicationsAlcohol abuse

Ultrasound(CT)

Confirm hepatic origin(serum GGT)

Dilated Bile DuctsSpace- occupying lesion

Algorithm for managing a patient in an Algorithm for managing a patient in an isolated increase in a serum Alkaline isolated increase in a serum Alkaline

PhophatasePhophatase

Makers of CholestasisMakers of CholestasisC.C. BilirubinBilirubin

- organic anion derived from the catabolism of hemoglobin- organic anion derived from the catabolism of hemoglobin- production is accelerated by hemolysis, ineffective erythoropoeisis- production is accelerated by hemolysis, ineffective erythoropoeisis1. Unconjugated Hyperbilirubinemia1. Unconjugated Hyperbilirubinemia-indirect bilirubin, lipid soluble ( 85%) -indirect bilirubin, lipid soluble ( 85%) - results from increased bilirubin production or inherited or acquired - results from increased bilirubin production or inherited or acquired defects in hepatic uptake or conjugationdefects in hepatic uptake or conjugation- seen in hemolysis- seen in hemolysis2. Conjugated Hyperbilirubinemia2. Conjugated Hyperbilirubinemia- direct bilirubin water soluble ( > 50%)- direct bilirubin water soluble ( > 50%)- results of inherited or acquired defects in hepatic excretion- results of inherited or acquired defects in hepatic excretion- useful prognostically in patients with alcholic hepatitis, primary - useful prognostically in patients with alcholic hepatitis, primary biliary cirrhosis, or accute liver failurebiliary cirrhosis, or accute liver failure

Increased serum bilirubin

Haemolysis(unconjugated)

Familial

Unconjugated Conjugated

Dubin-Johnson Rotor

Gilbert

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

Markers of Hepatic Synthetic Markers of Hepatic Synthetic CapacityCapacity

A.A. Prothrombin TimeProthrombin Time- Liver plays a crucial role in hemostasis- Liver plays a crucial role in hemostasis

Differential DiagnosisDifferential DiagnosisElevated PTElevated PT1. Vitamin K deficiency1. Vitamin K deficiency

- malnutrtion- malnutrtion- malabsortion- malabsortion- antibiotic use- antibiotic use

2. Warfarin administration2. Warfarin administration3. DIC ( Factor VIII)3. DIC ( Factor VIII)4. Liver Disease ( Normal or increase factor VIII)4. Liver Disease ( Normal or increase factor VIII)

Prolongation of PTProlongation of PT1. Decompensated liver disease ( with hepatocellular 1. Decompensated liver disease ( with hepatocellular

dysfunction)dysfunction)2. Chronic cholestatic disease2. Chronic cholestatic disease

Markers of Hepatic Synthetic Markers of Hepatic Synthetic CapacityCapacity

B.B. AlbuminAlbumin- 10 grams of albumin is synthesis and - 10 grams of albumin is synthesis and

secreated by hepatocytes each daysecreated by hepatocytes each dayFactors that affect albumin levelsFactors that affect albumin levels

1. Nutritional and volume status1. Nutritional and volume status2. Vascular integrity2. Vascular integrity3. Catabolism3. Catabolism4. Hormonal Factors4. Hormonal Factors5. Kidney disease5. Kidney disease6. Liver disease6. Liver disease

- serum albumin level correlates - serum albumin level correlates with prognosis in chronic liver diseasewith prognosis in chronic liver disease

Test (Normal Range)Test (Normal Range) Basis of AbnormalityBasis of Abnormality Associated Liver Associated Liver DiseasesDiseases

Extrahepatic SourceExtrahepatic Source

AminotransferasesAminotransferases

(10-55 U/L, 0.17-0.92 ukat/L (10-55 U/L, 0.17-0.92 ukat/L for ALT, 10-40 U/L, 0.17-for ALT, 10-40 U/L, 0.17-

0.67 ukat/L for AST)0.67 ukat/L for AST)

Leakage from damaged tissueLeakage from damaged tissue Modest elevation- many types of liver Modest elevation- many types of liver diseasedisease

Marked elevations- hepatitis (viral, Marked elevations- hepatitis (viral, autoimmune, toxic, and ischemic)autoimmune, toxic, and ischemic)

AST/ALT > 2 with the value of each AST/ALT > 2 with the value of each less than 300 U suggests alcoholic liver less than 300 U suggests alcoholic liver

diseases or cirrhosis of any etiology diseases or cirrhosis of any etiology

ALT, relatively specific for ALT, relatively specific for hepatocyte necrosishepatocyte necrosis

AST, muscle (skeletal and AST, muscle (skeletal and cardiac), kidney, brain, cardiac), kidney, brain,

pancreas, red blood cellspancreas, red blood cells

Alkaline phosphateAlkaline phosphate

(45-115 U/L, 0.75-1.92 (45-115 U/L, 0.75-1.92 ukat/L)ukat/L)

Overproduction and leakage Overproduction and leakage into seruminto serum

Modest elevations-many types of liver Modest elevations-many types of liver diseasedisease

Marked Elevations- extra- and intrahe- Marked Elevations- extra- and intrahe- patic cholestasis, diffuse infiltrating patic cholestasis, diffuse infiltrating

disease (e.g., tumor, MAC), disease (e.g., tumor, MAC), occasionally alcoholic hepatitisoccasionally alcoholic hepatitis

Bone Growth or disease (e.g. Bone Growth or disease (e.g. tumor, fracture, Paget’s tumor, fracture, Paget’s

disease), placenta, intestine, disease), placenta, intestine, tumorstumors

Gammaglutamyl Gammaglutamyl transpeptidasetranspeptidase

(0-30 U/L, 0-0.50 ukat/L)(0-30 U/L, 0-0.50 ukat/L)

?Overproduction and leakage ?Overproduction and leakage into seruminto serum

Same as for alkaline phosphate; induced Same as for alkaline phosphate; induced by ethanol, drugsby ethanol, drugs

GGTP/AP > 2.5 suggests (but not GGTP/AP > 2.5 suggests (but not diagnostic of) alcoholic liver diseasediagnostic of) alcoholic liver disease

Kidney, spleen, pancreas, Kidney, spleen, pancreas, heart, lung, brainheart, lung, brain

5’-Nucleotidase5’-Nucleotidase

(0-11 U/L, 0.02-0.18 ukat/L)(0-11 U/L, 0.02-0.18 ukat/L)

?Overproduction and leakage ?Overproduction and leakage into seruminto serum

Same as for alkaline phosphateSame as for alkaline phosphate Found in many tissues but Found in many tissues but serum elevation relatively serum elevation relatively specific for liver diseasespecific for liver disease

BilirubinBilirubin

(0.0-1.0 mg/dL, 0-17 umol/L)(0.0-1.0 mg/dL, 0-17 umol/L)

Decreased hepatic clearanceDecreased hepatic clearance Modest elevation- many types of liver Modest elevation- many types of liver diseasedisease

Marked Elevations- extra- and intrahe- Marked Elevations- extra- and intrahe- patic bile duct obstruction, alcoholic, patic bile duct obstruction, alcoholic,

drug-induced or viral hepatitis, inherited drug-induced or viral hepatitis, inherited hyperbilirubinemiahyperbilirubinemia

Increased breakdown of Increased breakdown of hemoglobin (resulting from hemoglobin (resulting from

hemolysis, ineffective hemolysis, ineffective erythropoiesis, resorption of erythropoiesis, resorption of

hematoma) or myoglobin hematoma) or myoglobin (resulting from muscle injury) (resulting from muscle injury)

Prothrombin timeProthrombin time

(10.9-12.5 sec) or (10.9-12.5 sec) or International Nromalized International Nromalized

Ratio (INR) (0.9-1.2)Ratio (INR) (0.9-1.2)

Decreased synthetic capacityDecreased synthetic capacity Acute or chronic layer liver failure Acute or chronic layer liver failure (unresponsive to vitamin K)(unresponsive to vitamin K)

Biliary obstruction (usually responsive Biliary obstruction (usually responsive to vitamin K administration) to vitamin K administration)

Vitamin K deficiency Vitamin K deficiency (secondary to malabsorption, (secondary to malabsorption,

malnutrition, antibiotics), malnutrition, antibiotics), consumptive coagulopathyconsumptive coagulopathy

AlbuminAlbumin

(4.0-6.0 g/dL, 40-60 g/L(4.0-6.0 g/dL, 40-60 g/L

Decreased synthesisDecreased synthesis

?Increased catabolism?Increased catabolism

Chronic liver failureChronic liver failure Decreased in nephrotic syndrome, Decreased in nephrotic syndrome, protein-losing enetrophaty, vascular protein-losing enetrophaty, vascular

leak, malnutrition, malignancy, leak, malnutrition, malignancy,

aodinflamatory statesaodinflamatory states..