Liver Function Tests

Liver Function Tests

Ramazan Idilman M.D., Professor in Medicine

Ankara University Faculty of Medicine

Department of Gastroenterology

Liver Anatomy

Liver

 Parencyhmal cells

 Hepatocytes

 Bile duct epithelial cells

 Sinusoidal cells

 Hepatic sinusoidal endothelial cells

 Kupffer cells

 Perisinusoidal cells

 Hepatic stellate cells

 Pit cells

Portal Triad

 Hepatic artery

 Portal vein

 Bile duct

Histology of the liver

Shematic Drawing of the Liver Architecture

Liver Cell Type and Its Relationship

The function of the liver

 Metabolic function

 Protein, carbohydrate and lipid metabolism

 Excretory function

 Bile, cholesterol

 Detoxification and protective function

Drug and toxin

 Synthesis function

 Albumin

 Storage function

 Glycogen

The function of the liver

 Metabolic function

 Protein, carbohydrate and lipid metabolism

 Excretory function

 Bile, cholesterol

 Detoxification and protective function

Drug and toxin

 Synthesis function

 Protein

 Storage function

 Glycogen

Role of liver function tests

 Screening for the presence of liver abnormality

 To asses the severity of disease

 To predict of disease outcome

 To evaluate the response of the therapy

 To follow the course of disease

Limitation of Tests

 Sensitivity and specificity are low

Liver injury tests

 Aminotransferases

 AST and ALT

 Since 1950, most sensitive markers for hepatocelluler injury.

have no function

Cytosol, mitochondria

Muscle, kidney, brain, pancreas, lung, leukocytes

 Increases in serum value

 Tissue damage

Changes in cell permeability

Limitation of Tests

 ALT is more specific indicator

 Cleared by cells in the RES

N: < 40 U/L

 Healty value: <30 U/L, <19 U/L

 The degree of elevation does not correlate

with extend of liver injury

Acute severe elevations

 Hepatic causes

Acute viral hepatitis

Toxic hepatitis

Acute Budd-Chiari Syndrome

Ischemic hepatitis

Acute bile duct obstruction

Autoimmune hepatitis

Wilson’ disease

 Nonhepatic

Acute Rhabdomyolysis

Chronic mild elevations

 Hepatic causes

Chronic viral hepatitis

Toxic hepatitis

Fatty liver

Metabolic liver disease

Autoimmune liver disease

 Nonhepatic

Hypo/hyperthyroidism

Myopathy

Celiac disease

Below normal

 No clinical importance

 Chronic renal failure

 Vitamin B

deficiency

 Malnutrition

Cholestatic Enzymes

 Alkaline phosphatase

 Gamma glutamyl transpeptidase

 5’-nucleotidase

Alkaline Phosphatase

 Cholestatic enzyme

 Isoenzymes

Liver

Canaliculer membran of hepatocytes

 Bone

Placenta

 Small intestine

Kidney

 Function is unknown

Alkaline Phosphatase

 Elevated level

 Hepatobiliary diseases

 Induction of enzyme synthesis

Leakage into the serum

 Elevation of the serum ALP, GGT and 5 nucleotidase

After a fatty meal

 In adolescent period

 Low level

Wilson’s Disease

Gamma Glutamyl Transpeptidase (GGTP)

 Cell membrane

 Liver

 Hepatocytes

Cholangiocytes

 Kidney

 Pancreas

 Heart

 Brain

 High sensitivity and low specificity

GGTP

 Elevated level

 Hepatobiliary disease

 Drug use

 Phenytoin, barbiturates

Alcohol use

5 nucleotidase

 Associated with canalicular and sinusoidal plasma membranes

 Found in the intestine, brain, heart, pancreas

 Elevated in hepatobiliary disease

Cause of Cholestatic Enzyme Elevations

 Intrahepatic

 Extrahepatic

Intrahepatic Cholestatic Enzyme Elevations

 Drugs

Autoimmune liver diseases

 Granulomatous liver disease

Viral hepatitis

 Idiopathic adult ductopenia

Genetic conditions

 Malignacy

Infiltrative liver disease

 Intrahepatic cholestatis of pregnancy

Sepsis

 Total parenteral nutrition

Extrahepatic Cholestatic Enzyme Elevations

 Intrinsic

Choledocholithiasis

 Malignancy

Immune-mediated duct injury

 Infections

 Extrinsic

Malignancy

Mirizzi’s syndorme

Pancreatitis

Lymphadenopathy

Psuedocyst

Tests of Hepatic Synthetic Function

 Albumin

 Prothrombin time

Albumin

 is synthesized exclusively by hepatocytes

15 g/day

 is responsible 75% of the plasma colloid oncotic pressure

 Excellent marker for hepatic synthetic function

 Half life is 14 to 21 days

 is regulated by

Nutritional status

 Ostomotic pressure

 Systemic inflammation

 Hormone levels

Hypoalbuminemia

 Differential diagnosis

 Hepatocellular dysfunction

 Malnutrition

 Protein-losing enteropathy

 Nephrotic syndrome

 Chronic systemic inflammatory conditions

Hormonal imbalances

Prothrombin Time

 All clothing factors are synthesis in the liver

 Except factor VIII

 Prothrombin time measures

 reflects the extrinsic pathway

 Factror II, V, VII, X

 INR standardizes prothrombin time

Prolonged Prothrombin Time

 Hepatocellular dysfunction

 Congential deficiency of clotting factors

 Vitamin K deficiency

 Disseminated intravascular coagulation (DIC)

 Factor VIII levels

Measurement of Prothrombin Time

 Acute liver failure

 Half time is very short

 Six hours for Factor VII

 King’s College Criteria

 Chronic liver failure

 Prognostic indicator

 Child Pugh Score

 MELD score

Tests of Detect Hepatic fibrosis

 Liver biopsy

 Standard for the assessment of fibrosis

 Serum biochemical markers

 Hyaluronan

 Fibrotests

 Haptoglobulin, bilirubin, GGTP, apolipoprotein A-1

 Alpha-2 macroglobulin

 Transient elastography: Fibroscan

 Magnetic resonans elastography

Quantitative Liver Function Tests

 To evaluate the excretory and detoxification capacity of the liver

 Better than serum bilirubin level

 Such as

 Indocyanine Green Clearance

 Galactose Elimination Capacity

Caffeine Clearance

 Lidocaine Metabolite Formation

 Aminophrine Breath Test

Bile Acids

 is synthesized by cholesterol in the liver

 conjudated tp glycine or taurine

 secreted into bile

 reabsorbed in the small intestine

 Sensitive indicator for hepatic dysfunction

 are elevated in cholestatic liver diseases

Evaluation of asymptomatic elevations

aminotransferase levels

Evaluation of Cholestatic Liver Enzyme

Elevations