LIVER FUNCTION TEST

• DR.dr.Tinny Rasjad Indra

Liver hilang ¼ bagian ~ masih bisa kompensasi

CANALICULUS
BILIARIS

SINUSOID

SEL HATI
 LIVER CELL

(CONJUGATED)

CONJUNGGATED BILIRUBIN

SINUSOID

BILE DUCT
UN CONJUNGGATED BILIRUBIN
• Unconjugated  Hasil dari perpecahan
hemoglobin ~ heme + globin
 Beredar dalam liver  diubah jadi
conjugated
Hepatic function

Complexs
• Cholesterol Sinthese
• Energy : Stores and • Detoxification
transports – External: Alcohol
• Glucose control – metab: Bilirubin
– glycogen – drug
• Regulator lipid • Sinthese vitamin:
• Production Bilirubin Vitamin D
• Sinthese • Material stores : Fe
– Coagulation factors
– Blood protein
• Hormon sinthese
 Cause hepatal damage
• A Autoimmune hepatitis
• B Hepatitis B
• C Hepatitis C
• D Drugs or toxins
• E Ethanol / Hep E (kehamilan)
• F Fatty liver
• G Growths (i.e., tumors)
• H Hemodynamic disorder (congestive heart failure or
“shock liver”)
• I Inborn errors - iron (hemochromatosis),
 What are the clinical manifestations?
 The most common of clinical manifestation of liver disorder
is jaundice (icterus), but not all of the liver disorder cause
icterus

 If jaundice is present, what should we do?

 Determine the type of icterus
 ( HEMOLYTIC, OBSTRUCTIVE, PARENCHYMATOUS )

 Laboratory Examination  liver disorder or not?

 Determine:
 Severity ,
 Acute or chronic
 etiology (example: serologic Test)

If important, we can use USG, etc

• Ikterus hemolitik ~ pre hepatik ( perpecahan
eritrosit sebelum waktunya )  penumpukan
Fe  ikterus
• Ikterus obstruktif ~ setelah lewat hepar ,
pembuntuan sal.empedu
Ekstra ~ tumor, batu, hal-hal yg menekan
sal.empedu *diluar hepar
Intrahepatal  parenkimatus ~ hepatitis
Laboratory Examination of Liver Function
 Examination hepatic cell damage
1. SGPT EXAMINE LIVER CELL INTEGRITY
2. SG OT

 Examination of Synthetic Function of the liver

1. ALBUMIN ~ ↓ pada gx hepar
2. CHOLIN ESTERASE
3. PPT
4. CHOLESTEROL

 Examination of Excretion Function of the Liver

1. ALP
2. Gamma GT
3. BILIRUBIN
 SERO MARKER Ex , HBs Ag, Anti HBs,
Anti HBc, HBe Ag,
Anti Hbe, HBV-DNA

 TUMOUR MARKER
1. ALFA FETO PROTEIN
2. CARSINO EMBRYONIC ANTIGEN
3. PIVKA II
• HBs Ag ~ Hepatitis B Surface Antigen
• HCV ~ Hepatitis C Virus
• Anti HBc ~ Anti Hepatitis B core
Examination hepatic cell damage
 SGOT ( AST ) – SGPT ( ALT )
• SGPT ( ALT )
– PRODUCED IN LIVER
– LOCATED IN THE CYTOPLASM OF HEPATOCYTE
– MORE SPESIFIC FOR LIVER DIASEASE

• SGOT ( AST )
– PRODUCED IN LIVER AND MUSCLE
– LOCATED BOTH IN CYTOPLASM AND
MITOCHONDRIA OF HEPATOCYTE

• SGOT / SGPT RATIO

– < 1  MILD DAMAGE/ NORMAL
– > 1  SEVERE DAMAGE
– EXP : SGOT =150 , SGPT = 90  RATIO >1
( intracelluler damage )
 SGPT

SGOT

SGOT

OT/PT RATIO < 1 mild damage

OT/PT RATIO > 1 severe damage

 EVALUATION OF HEPATOCYTE INTEGRITY
(SGOT – SGPT)

• SGPT :
– Increase > 500 IU/L 
• Acute Hepatitis  bisa meningkat sampai ribuan
• Drugs Intoxication
• Ischaemia

– Increase < 300 

• Acute Hepatitis
• Chronic Hepatitis
• Biliary Obstruction
• Peningkatan SGOT kalo cuma 5 , bisa aja error
atau kecapean
• Meningkat 10-100x lipat baru curiga!!

• IU ~ satuan aktivitas enzim

• SGOT SGPT  suatu enzim
Examination of Synthetic Function
of the liver
 ALBUMIN
 Decrease in severe/ chronic liver disease
 Describe synthetic function of liver

 Lowering albumin will be followed by

increasing globulin and gamma globulin
 N ( albumin) : 3,8- 5,2 gr %
 Level < 3 gr %  severe

 Not spesific  another disease have same

appearance :
 renal disease, malnutrition
 Plasma cell dyscrasia.
 CHOLIN ESTERASE
• plasma enzyme
• Produced by hepatocyte
• Is index to know synthetic function of liver

• If normal  good function

• If decrease 
– Abnormal liver function, malnutrition
– cirrhosis, anemia, ca.

• Not useful to:

– Patients with increasing synthetic function :
• thyrotoxicosis,
• Nefrotik syndrome
• alcoholic fatty liver.
 COAGULATION
• ALL OF COAGULATION FACTOR synthesized
by liver
• vit K dependent coagulation factor :
II,VII,IX,X

• Defficiency of these factors  prolonged PPT (

EXTRINSIC PATHWAY)

• If abnormal PPT become normal with vit K

treatment  respect that this abnormality not
caused by liver disease (but from vit K
defficiency)
Aptt ~ IX, X prolonged
PTT ~ VII prolonged
 BLOOD COAGULATION

IX

PPT

X
V

II
I

VIT K DEPENDENT
2.7.9.10
Examination of Excretion Function
of the Liver
(obstruction)
 ALKALI PHOSPATASE (EXCRETION FUNCTION)
L:6-28U/L
P:4-18 U/L

 PRODUCED IN:
 LIVER ( bile canaliculi, sinusoid ) 
(excretion function)
 PANCREAS, INTESTINE, BONE

 Differentiated by examining another

LFT  if another LFT increased, the
increase of ALP is from liver

**kurang spesifik
 IN BILE DUCT OBSTRUCTION (
STONE/ TUMOUR)  ALP >>
** ALP u/ post-hepatal

 INCREASING ALP >350 ng/ml 

suspect carcinoma

 CHILDREN – PUBERTY OR
PREGNANT WOMAN ALP
INCREASE 2-2,5  NORMAL.
 GAMMA-GT
• LOCATED IN: LIVER, KIDNEY, PANCREAS.
• found primarily on the canalicular surface of the hepatocyte
• Increase highly in biliary tractus obstruction and hepatocarcinoma

• INCREASE IN LIVER DISEASE DUE TO:

– ALCOHOL
– BARBITURATE
– DECOMPENSATIO CORDIS
– INFECTION

• IN CLINICAL PRACTICE, ALP ASSAY COMBINED WITH GGT

– ALP ↑, G-GT NORMAL  BONE DISORDER
– ALP ↑ & G- GT ↑  CHOLESTASIS

• SENSITIVE, EARLY APPEAR, LATELY RETURN

• GGT lebih spesifik dari ALP
• ALP pada anak cenderung lebih tinggi ( 2-2,5x
N)
 BILIRUBIN

>3 baru muncul ikterus

Jaundice
 BILIRUBIN

FE

HEME

UNCONJUNGGATED
PORPIRIN BILIRUBIN
ERI

GLOBIN
 Bilirubin
• There are two kinds:
– Unconjungated
– Conjungated

• Unconjugated bilirubin unsoluble in water 

bilirubin urine is negative

• Conjugated bilirubin  water soluble  bilirubin

urine is positive.
 Formation of bilirubin:
1. RBCs are phagocytized in the spleen. Hemoglobin
is catabolized into globin(amino acids) , iron and
heme.

2. Heme ring is broken open and converted to

unconjugated (indirect )bilirubin.

3. RE cells in the spleen secrete unconjugated

bilirubin into the plasma, where bilirubin is bound
by albumin.

4. Albumin – bilirubin complex travels to the liver.

 Continue ………
1. Hepatocytes conjugates bilirubin with
gluconic acid and UDPG enzyme.

2. Conjugated bilirubin secreted into the bile

ducts ( GI tract )

3. GI bacterial normal flora convert

conjugated bilirubin into urobilinogen.
4. Urobilinogen excreted into the stool, the
urine
 RES
UNCONJUGATED
BILIRUBIN
BLOOD
REN
CONJUGATED
LIVER
BILIRUBIN

PORTAL
BILIARY TREE VEIN

INTESTINES URINE

FESES
 Indirect Bilirubin

• Result of Heme breakdown

–Hemolysis from any cause is common
source
–Check CBC, smear, and Retic count
• Hepatocellular damage
–Elevated indirect combine direct bili
 Anemia hemolitik ~ kelainan
intrahepatal
• Autoimun ~ produksi bagus, begitu pecah,
membuat baru terus, retikulosit meningkat di
sirkulasi

** prehepatic ~ indirect
*intrahepatic ~ direct & indirect
** posthepatic ~ direct
 Direct Bilirubin
• Liver disease mainly impairs the
secretion of conjugated bilirubin into
bile

• Serum conjugated bilirubin level does

not become elevated from liver
disease until the liver has lost at least
one half of its excretory capacity.
• Mulai periksa bilirubin kalo fx hepar tinggal ¼,
kalo ½ masih bisa berfx walopun menurun
• Increased plasma bilirubin indicates
– Increased RBC destruction
– Decreased hepatic conjugation and excretion of
bilirubin
• Jaundice
– Yellowish discolorization of the skin and sclera from
increased plasma bilirubin
• Icteric
– Plasma / serum with yellowish color from ↑ bilirubin
• Reference ranges
– Total Bilirubin ( conjugated + unconjugated) 0.2 - 1.0 mg / dl
– Conjugated bilirubin 0.0 - 0.02 mg / dl
– Fullterm newborns 2.0 – 6.0 mg / dl
– Jaundice is evident at 3.0 mg / dl
• Jaundice ~ klinis pada manusia
• Ikterik pada sampel darahnya
• Jaundice kalo >3mg/dl
 Hyperbilirubinemia
Hyperbilirubinemia (Jaundice)

Prehepatic
Hepatic Posthepatic
(Hemolysis) (Genetic defects, (Bile Duct Obstruction,
primary liver disease) Pancreatic Head CA)

Unconjugated Mixed Conjugated

Bilirubin Bilirubin
• General classifications of jaundice
– Prehepatic
• Excess RBC destruction ( Not impaired liver function
)
–Increased unconjugated bilirubin
– Hepatic
• Defective liver function ( most common )
• Defective hepatocyte uptake ( conjugation ) secretion
of bilirubin
• Cholestasis – Impaired hepatic transport
– Increased unconjugated bilirubin + conjugated
– Posthepatic
• Impaired ability of liver to excrete bile into the GI tract
(gallstones, tumors )
–Increased conjungated bilirubin
 Excessive RBC destruction

– Hemolytic anemias
• Hepatic inability to conjugate and
excrete bilirubin
• TBIL usually < 5.0 mg / dl
• “Pre-hepatic” jaundice“
• ↑ Total Bilirubin … ↑ Unconjugated
… Normal conjugated
• Negative Urine Bilirubin
• Heriditer
– Gilbert’s Syndrome
• Defective bilirubin transport into hepatocyte
(TBIL< 3.0 mg/dl)
– Crigler – Najjar Syndrome
• UDPG deficiency
• Hepatocytes lack UDPG enzyme – cannot
conjugate bilirubin
• Physiological Jaundice of the newborn
• Immature liver at birth
• Temporary deficiency of UDPG
• Small / moderate elevated unconjugated bilirubin lasting a
few days
Prehepatic (hemolytic) jaundice
 Results from excess
production of bilirubin
(beyond the livers
ability to conjugate it)
following hemolysis

 Bilirubin uri neg

 Urobilin pos
 High plasma
concentrations of
unconjugated bilirubin
(normal concentration
~0.5 mg/dL)
 Causes of Cholestasis
• Obstruction
– Intrahepatic
• Primary Biliary Cirrhosis – young females.
• DRUGS – any number of medications,
particularly antibiotics
– Extrahepatic
• Common duct obstruction (stone/Tumor)
–Primary Sclerosing Cholangitis
–Pancreatic head obstruction (Stone/Tumor)
Intrahepatic jaundice
 Impaired uptake,
conjugation, or secretion
of bilirubin
 Reflects a generalized
liver (hepatocyte)
dysfunction

 Urine: urobilin +
bilirubin +

 In this case,
hyperbilirubinemia is
usually accompanied by
other abnormalities in
biochemical markers of
liver function
Posthepatic jaundice  feses putih, keras (dempul)
 Caused by an obstruction of the
biliary tree

 Plasma bilirubin is conjugated,

and other biliary metabolites,
such as bile acids accumulate in
the plasma
 Urine: URO neg
Bilirubin pos

 Characterized by pale colored

stools (absence of fecal
bilirubin or urobilin), and dark
urine (increased conjugated
bilirubin)

 In a complete obstruction,
urobilin is absent from the urine
CONJUGATED BILIRUBIN
UNCONJUGATED

DIRECT INDIRECT
WATER SOLUBLE WATER INSOLUBLE
ESTERFIED NON-ESTERFIED
FOUND IN URINE NOT FOUND IN URINE
DOESN’T NEED ACCELERATOR NEEDS ACCELERATOR

TOTAL BILIRUBIN = CONJUGATED + UNCONJUGATED BILIRUBIN

LABORATORIES ROUTINLY MEASURE TOTAL BILIRUBIN ( TBIL ) AND

CONJUGATED BILIRUBIN ( DBIL ) . UNCONJUGATED BILIRUBIN IS
CALCULATED BY:

TBIL – DBIL = UNCONJUGATED BILIRUBIN

• Kalo conjugated bisa langsung diperiksa, tapi
kalo unconjugated perlu esterifikasi ( indirect )
• Bilirubin specimen requirements

– Serum / plasma
– Protect from light - Bilirubin is light
sensitive
– Hemolysis causes false increased
bilirubin