Liver Function Tests
รองศาสตราจารย์ แพทย์ หญิงพรรธนมณฑน์ อุชชิน
ภาควิชาเวชศาสตร์ ชันสู ตร คณะแพทยศาสตร์
จุฬาลงกรณ์ มหาวิทยาลัย
วัตถุประสงค์ : หลังจากเสร็จสิ้นการเรียน นิสิตสามารถ
1. อธิบายลักษณะทั่วไปของตับ
2. เข้ าใจหน้ าทีส่ าคัญของตับ(Major Functions of the Liver)
3. แยกชนิดและอธิบายการเกิด Jaundice ชนิดต่ างๆ ในร่ างกาย
4. เข้ าใจ Pathway of Bilirubin
5. รู้ จักInherited Disorders of Bilirubin Metabolism
6. รู้ จกั ชนิดต่ างๆของ LFTs
7. เข้ าใจหลักการและแปลผล routine LFTs ทีเ่ ลือกได้
8. อธิบายสาเหตุและเลือกใช้ LFTs ทีเ่ หมาะสมสาหรับโรคตับและทางเดิน
นา้ ดีทพี่ บบ่ อยๆได้
9. แปลผล LFTs ทีเ่ ลือกใช้ ได้
LIVER
Blood supply 15 ml/min :
Portal vein, Hepatic artery
 Parenchymal cells : Hepatocyte
 Nonparenchymal cells : Endothelial cells
Kupffer cells
Hepatic stellate cells
Pit cells
Hypoglycemia

Major Functions of the Liver
1.
Synthesis and metabolism of
proteins,carbohydrates and lipids
2.
Production, metabolism and excretion of
bile
Detoxification and drug metabolism
Enzymes synthesis
Storage of vitamins and minerals
3.
4.
5.
6.
7.
Biotransformation or Inactivation of
hormones
Phagocytosis
Synthesis & metabolism
of
proteins,carbohydrates and fats
90 % of plasma protein
(
except for gammaglobulin, hemoglobin )
nutrition, oncotic pressure, transportation
glycogenesis, glycogenolysis, glycolysis,
gluconeogenesis
triglycerides, VLDL, LDL, HDL, cholesterol
Production, metabolism and excretion of bile
 น้ำดี : bilirubin, bile acids / salts, electrolytes,
cholesterol, fatty acids, น้ำ, lecithin
 primary bile acids : cholic, chenodeoxycholic
acids
 secondary bile acids : deoxycholic, lithocholic
acids
 enterohepatic circulation
 bilirubin : hemoglobin, myoglobin, cytochromes,
catalase
 unconjugated bilirubin ( + albumin )
Production, metabolism and excretion of bile

Protein Y & Z , Ligandin

UDPG - T ( Uridyldiphosphate glucuronyl
transferase )
 conjugated bilirubin ( + glucuronic acids )

urobilinogen, stercobilin

biliprotein ( delta bilirubin )

jaundice / icteric ( TB > 2.5 mg /dl )
Jaundice classified by origin
1. Prehepatic ( TB < 5 mg/dl) :
Hereditary hemolytic processes
Acquired hemolytic processes
Ineffective erythropoiesis
Impaired delivery of bilirubin to the
liver
Sport injuries
Jaundice classified by origin
2. Hepatic :
Pre - microsomal
Microsomal
Post - microsomal
Intrahepatic obstruction
3. Posthepatic :
CBD stones
Cancers of the bile ducts, pancreas
Stricture, stenosis, atresia
Cholagitis, Choledochal cysts
Physiological classification of Jaundice
1. Unconjugated Hyperbilirubinemia
Production
Delivery to hepatocyte
Uptake across hepatocytic membrane
Storage in cytosol
Conjugation
Physiological classification of Jaundice
2. Conjugated Hyperbilirubinemia
Secretion into canaliculi
Drainage
Intrahepatic obstruction
Septicemia, total parenteral nutrition
Drugs
Inherited Disorder of Bilirubin Metabolism
Gilbert’s syndrome :
mild fluccuate unconjugated hyperbilirubinemia
conjugation +/- uptake
normal lifespan
Crigler - Najjar syndrome :
severe unconjugated hyperbilirubinemia
Type I : absence of UDPG - T
Type II : partial defect of UDPG - T
Inherited Disorder of Bilirubin Metabolism
Dubin - Johnson syndrome :
mild fluccuate conjugated hyperbilirubinemia
hepatic excretion
normal lifespan
hepatic pigmentation, bilirubinuria
Rotor syndrome :
unknown defect
similar to Dubin - Johnson syndrome
no hepatic pigmentation
Detoxification and Drug Metabolism
Phase I :
oxidation, hydroxylation
Phase II :
conjugation with glucuronic acid, glycine,
taurine and sulfate
Cytochrome P450 and allied hepatic enzyme
system
Epoxide hydrolase
UDP - glucuronosyl transferase
Sulphotransferase
Glutathione S - transferase
Enzymes Synthesis
Cytoplasmic enzyme :
AST(SGOT), ALT(SGPT), LD
Mitochondrial enzyme :
AST
Canalicular enzyme :
ALP, GGT
Storage of Vitamins and Minerals
Fat soluble vitamins ( A, D, E, K )
Vitamin B12
Iron
Copper
Biotransformation or inactivation of hormones
Somatomedin
Glucagon
Phagocytosis
Kupffer cells
Pit cells
LIVER FUNCTION TESTS
1. Routine ( Conventional ) LFTs
bilirubin, urobilinogen, ALP, AST, ALT, GGT
2. True tests of liver function ( QLFTs :
Quantitative LFTs )
Dynamic test ; measure metabolite / excretion rate,
liver blood flow or functional hepatic mass
QLFTs
Metabolic Capacity :
Indocyanine Green ( ICG ) test
14C- Galactose breath test
Microsomal enzyme function :
Aminopurine breath test
Caffeine breath test
Functional hepatic perfusion :
Galactose tolerance test
ICG ( low dose ) test
Microsomal enzyme function and hepatic perfusion :
Lidocaine clearance test
LIVER FUNCTION TESTS
3. Provide information about severity and
prognosis
TP, Alb, Clotting factors, Ammonia
4. Special laboratory tests
Alpha-1-antitrypsin, Alpha-fetoprotein, Autoantibodies
Ceruloplasmin, Copper, Hepatitis markers
Immunoglobulin, Iron and ferritin, Glutamine,
LD
Serum Bilirubin
Newborn
(Direct spectrophotometric method)
> 1month
(Colorimetric Wahlefeld method)
Urobilinogen in urine & feces
Urinary urobilinogen
Hemolytic disease
Viral hepatitis
Fecal urobilinogen
Biliary obstruction
Hepatocellular disease
LIVER ENZYMES
Principles of Diagnostic Enzymology
Half - life of liver enzymes in serum
ALP ………..3 - 7 วัน
ALT……….. 50 ชั่วโมง
AST…………12 - 14 ชั่วโมง
GGT………..7 - 10 วัน
Factors affecting enzyme levels in serum
1. Leakage of enzymes from cells
Hypoxia, Chemicals and drugs, Physical agents,
Microbiological agents, Immune mechanisms,
Genetic defects, Nutritional disorders
2. Altered enzyme production
3. Clearance of enzymes
average half - life in serum 6-48 ชั่วโมง
Characteristics of Elevated Concentration
Mild :
AST, ALT, GGT < 2 - 3 x URL
ALP < 1.5 - 2 x URL
Moderate :
AST, ALT up to 20 x URL
GGT up to 10 x URL
ALP up to 5 x URL
Marked :
AST, ALT > 20 x URL
GGT > 10 x URL
ALP > 5 x URL
AST &ALT
Mild :
Fatty liver
NASH ( Nonalcoholic steatohepatitis )
Chronic viral hepatitis
Marked :
Acute viral hepatitis
Drug or Toxin induced hepatic necrosis
Ischemic hepatitis
AST &ALT
> 2 : Alcoholic liver disease
> 1 : Cirrhosis
< 1 : NASH
Viral hepatitis
Aspartate Transaminase (AST,SGOT)
UV assay : Pyridoxal phosphate
Tissue Sources : cardiac tissue, liver, skeletal
muscle, kidney, pancreas, RBC
Sources of Error : hemolysis
Diagnostic Significances : Cardiac disease,
Hepatobiliary disease, Major crush injuries,
Skeletal muscle disease, Pancreatitis, Delerium
tremens.
Pregnancy
Alanine Transaminase ( ALT,SGPT )
UV assay : Pyridoxal phosphate
Tissue Sources : liver
Sources of Error : hemolysis
Diagnostic Significances :
Hepatobiliary disease, Heart failure with
hepatic necrosis
Alkaline Phosphatase ( ALP )
ALP > 3 x URL
Hepatobiliary disease ( cholestasis )
Marked increase
Extrahepatic biliary obstruction
PBC ( Primary Biliary Cirrhosis )
PSC ( Primary Sclerosing Cholangitis )
Drug - induced cholestasis
Mild - moderate increase
Amyloidosis
Granulomatous disease
Neoplasms, Hodgkin’s disease
Renal cell carcinoma
Alkaline Phosphatase ( ALP )
Colorimetric assay : ++Mg
Tissue Sources :
intestinal epithelium, liver (sinusoidal and bile
canalicular membrane), bone (osteoblast),
kidney tubules, placenta, spleen
Sources of Error :
phosphate, borate, oxalate, cyanide, Lphenylalanine, urea, hemolysis
Diagnostic Significances :
Hepatobiliary disease, Bone disease, Healing
fracture, Normal growth,Pregnancy
Hereditary hypophosphatasia
Alkaline Phosphatase ( ALP )
Diagnostic Significances
Isoenzymes ; liver(heat stable), bone(heat labile),
intestinal and placental
Placenta-like ( Regan & Nagao ) ; germ cell
tumors, seminoma, serous carcinoma of ovary,
endometrial carcinoma and leukemia
- Glutamyl Transferase ( GGT )
Enzymatic Colorimetric assay
Tissue sources :
cell membrane and mitochondria
Sources of Error :
smoking, pregnancy, alcohol, phenytoin,
barbiturate, carbamazepine, valproic acid,oral
contraceptive
- Glutamyl Transferase ( GGT )
Diagnostic Significances :
),
Hepatobiliary disease,
Hepatic microsomal enzyme induction
( drugs ; warfarin, phenytoin, phenobarbital
Alcoholism and heavy drinking, Pancreatitis,
Diabetic mellitus, Congestive cardiac failure
Lactate Dehydrogenase ( LD, LDH )
UV assay
Tissue Sources : myocardium, kidney, liver,
skeletal muscle and RBC
Sources of Error : hemolysis
Diagnostic Significances :
AMI, Hepatobiliary disease,Renal disease,
Cancers, Anemia, Progressive muscular
dystrophy,
Isoenzymes( LD1,2,3,4,5 )
Liver Enzymes
Routine
AST, ALT, ALP
Liver specific
OCT (Ornithine Carbamoyl Transferase)
ID (Iditol Dehydrogenase), Guanase
hepatic isoenzyme of ALP
Liver Enzymes
Interpretation
AST&ALT ………..hepatocellular damage
ALP…………………cholestasis
Plasma Proteins
Colorimetric assay
Hyperproteinemia : Dehydration, Liver
diseases, Chronic inflammatory diseases,
Increased plasma immunoglobulins, Faulty
technique in blood sample
Hypoproteinemia : Overhydration,
Pregnancy, Malnutrition, Liver diseases,
Protein loss, Hypogammaglobulinemia,
Hyperthyroidism
Albumin
Colorimetric assay : Dye-binding method
Sources of Error : hemolysis
Hypoalbuminemia : Hereditary defects,
Malnutrition, Malabsorptive disease, Severe
burn, Shock, Chronic liver disease, Major
surgery, Accidental trauma, Infection, Renal
disease, Exfoliative dermatitis
Protein-losing gastroenteropathy,
Clotting Factors
Quick’s One Stage Prothrombin Time or
Plasma Prothrombin Time
Extrinsic pathway
Factors : I, II, V, VII, X
INR ( International Normalized Ratio )
Ammonia
Enzymatic kinetic assay
EDTA plasma, hemolysis, protein in food,
drugs, exercise
Diagnostic Significances ; Reye’s
syndrome, Liver disease, Cirrhosis, Hepatic
coma, Hyperornithinemia
Unexplained lethargy and vomiting,
Encephalitis & Neonate with unexplained
neurologic deterioration
Ceruloplasmin(CERU; Cp )
Ferrioxidase activity, acute phase protein
Immunoturbidimetric method
Serum, heparinized plasma, hemolysis, lipemia &
rheumatic factors
Diagnostic Significances ; Wilson’s disease,
Monkes disease, Nutritional copper deficiency,
Renal copper loss, Massive burn, Inflammation
disease, RE neoplasia, Biliary obstruction,
Estrogen therapy, Pregnancy
Most Common Disease of Liver
1. Hepatitis :
Acute ( viruses, toxins and drugs )
recovery from viral hepatitis ...transaminases
are normal within 10-12 weeks
( > 6 months ………chronic )
Chronic ( autoimmune, viruses, alcohol and
drugs ) : normal ALP, increased AST&ALT
abnormal Albumin & PT
Most Common Disease of Liver
2. Cirrhosis :
Chronic excessive alcohol intake
Autoimmune chronic active hepatitis
Chronic hepatitis B, C, D,
Inherited metabolic disease : Wilson’s disease, DM,
Glycogen storage disease, Galactosemia
Disease of Prolonged Cholestasis : PBC, PSC,
Cystic fibrosis, Biliary atresia
*decompensated cirrhosis…increased blood
ammonia
Most Common Disease of Liver
3. Tumours
Metastatic : primary sites ; lung, bronchus,
breast, gastrointestinal tract, prostate gland
*normal TB, AST, mild increases of GGT and ALP
with marked increase of LD
Hepatoma : Cirrhosis, Hepatitis B, C, Aflatoxins
*increases of alpha-fetoprotein and ALP
Differential of Hepatocellular Injury and Cholestasis
Test
Hepatocellular Injury
Cholestasis
ALT
> 10 x URL
< 10 x URL
ALP
< 3 x URL
> 3 x URL
GGT
< 5 x URL
> 5 x URL
Bilirubin
DB 50-80%
DB 50-80%
PT
No
Respond to Vit K
Imaging studies
Normal ducts
Abnormal ducts
Pattern of Cholestasis
Bilirubinostasis………… Hepatocyte
Cholestatic hepatitis……Canalicular
Ductular injury……………Intrahepatic bile ducts
Complete obstruction… Extrahepatic bile ducts
Some Drugs causing liver
diseases
Hepatotoxicity
Cholestasis
Cholestatic hepatitis
Paracetamol (overdose) Methyltestosterone Chlorpromazine
Salicylate( high dose)
Erythromycin
Tetracycline ( high
Chlorpropamide
dose)
Rifampicin
Comments for Interpretation of LFTs
1. Definite diagnosis : special tests or liver
biopsy
2. ALP, GGT and 5’- NT
3. Moderated or marked increase of ALP
4. AST, ALT > 10 x URL… hepatocellular
damage
5. ALP > 3 x URL….cholestasis
Comments for Interpretation of LFTs
6. Prolongation of PT
a.  vitamin K…Advanced liver destruction
b.  vitamin K…Vitamin K deficiency or
Long-standing extrahepatic obstruction
7. Bile acids analysis….Inactive cirrhosis
8. Liver scan……Metastatic carcinoma
9. U/S & PTC….Extra / intrahepatic obstruction
10. Repeat LFTs …..2 -3 days
Thank you for your
attention