JANET LIM-DY, M.D., F,P.S.P. D.T.M.H.

EVALUATION OF
LIVER FUNCTION
TESTS
 Overview
3 Systems involved in understanding
liver function tests:

Hepatocyte
•Proteins synthesis
•Coagulation factors
Biliary Tract: bili metabolism
synthesis

RES: Immune sys. , Heme &

globin metabolites
 KREBS FA SYNTHESIS & BREAKDOWN
CYCLE
LIPOPROTEIN METABOLISM
GLUCONEOGENESIS AA & NUCLEIC ACID METABOLISM
GLYCOLYSIS
HMP-SHUNT
2 GENERAL METABOLIC PATHWAYS:
1. AA-CHO PATHWAY
involves ALT & AST
2. UREA CYCLE
NH4 urea
Enzyme OCT unique to liver
LIVER FUNCTION TESTS

hepatic structure,
cell integrity,
 function
 LIVER FUNCTION TESTS
Reasons for requesting LFT:
1. For Diagnosis
2. For Differentiation
Is Hepatic damage due to primary
hepatocyte damage or biliary system
obstruction?
3. Prognosis / Monitoring
TESTS FOR DISCLOSING
HEPATIC DYSFUNCTION
Liver Enzymes
Aminotransferases (ALT and AST)
Lactate Dehydrogenase (LDH)
Alkaline Phosphatase (Alk Phos)
 Glutamyl transferase (GGT)
TESTS FOR DISCLOSING
HEPATIC DYSFUNCTION
Total Protein
Albumin
Gamma Globulins
Alpha Globulins
Clotting Factors
ProthrombinTime
HEPATOBILIARY DYSFUNCTION
 Serum Bilirubin ( total & direct)
PATIENT PREPARATION &
SPECIMEN COLLECTION
No special preparation required
Serum : Preferred Specimen
Heparinized Plasma : Acceptable
 Liver Enzymes: Transaminases

 2 major aminotransferases
 AST(SGOT) – Aspartate transferase
 ALT(SGPT) – Alanine transferase

 Catalyze reversibly the transfer of an amino gr.of either

AST or ALT to alpha-ketoglutarate to yield glutamate
plus the corresponding ketoacid of the starting a.a.
 Liver Enzymes: Transaminases
Reaction catalyzed by ALT

COOH CH3 COOH COOH

| + | B6 | |
CH2 H C- NH3 CH2 C=O
| | | |
CH2 + COOH CH2 + COOH
| | pyruvate
C=O C- NH3
| |
COOH COOH
-ketoglutarate L-alanine L-glutamate
 Transaminases
Distribution:
AST
ALT: liver (1o location)
kidney & muscle (lesser
quantity)
AST
more liver-specific
cytoplasmic enzyme
ALT
AST : in many body tissues,
ex heart,liver,muscle,RBC
brain,lung ,pancreas &
kidney.
cytoplasmic & mitochon
drial enzyme
Elevation of ALT activity
persist longer
Reference value
 ALT :
Males 10-40 U/L
Females 7-35 U/L

 AST :
Males 15-40 U/L
Females 13-35 U/L
 Transaminases In
Hepatobiliary Diseases
Hepatocellular injury
AST

Mild: AST
Cytoplasmic AST & ALT
ALT released into serum
PM damaged
ALT
Mitochondrial AST
released into serum:
More severe:
Disproportionate
Mitochondrial AST
80% elevation----
membrane
(De Ritis quotient)
damaged
 AST/ALT (DeRitis) ratio: to
discriminate alcoholic hepatitis vs
other liver diseases ;
Sometimes help determine whether
the liver is damaged or another
organ has been damage
How to calculate AST/ALT ratio?
ex. AST= 52, ALT =67
52/67 = .75
AST / ALT > 2 ( 3:1 to 4:1) = ALD
AST/ALT <1,most likely assoc. with
other cause eg. Viral hep
 Transaminases

acute hepatitis : ALT is more increased than AST

(20 -100 x the upper limit)
AST is 10x the upper limit
5-10x the upper limit in liver Ca
Cirrhosis : ALT is more increased than AST, but as
fibrosis progresses, ALTdec. In end stage = both enzymes
are dec.
Acute Fulminant hepatic failure,;AST : ALT > 1
AST value > 1000 = severe liver necrosis, AMI
TRANSAMINASES
REMEMBER: Levels are often compared
with results of other LFTs to help determine
which form of liver d’s is present
In most type of liver d’s ,ALT level > AST
AST/ALT ratio is low
AST : use for monitoring tx of potentially
hepatotoxic drugs
> 3x ULN  stop tx
 Transaminases In
Asymptomatic Patients
Possible Causes of Chronic Elevation:
1. Alcohol or medication use
2. ChronicViral Hepatitis
3. Non-alcoholic fatty liver disease
4. Overweight (inc.ALT)
 LIVER ENZYMES :
LACTATE DEHYDROGENASE
Cytoplasmic enzyme
Non specific for liver LD4
Distribution of LD5
isoenzymes- LD1,LD2
LD1
Cardiac muscle, LD1,LD
TRANS LD2
LD2 kidney,rbc
LD4 Liver, skeletal LD
LD5 muscle LD4,LD5

N value(TLD) =150 IU/l

 LIVER ENZYMES :
LD in Hepatitis
Is slightly inc. but only
transient ( low activity and
short half life
Large increment of total
LD= 500 -1000 iu/l
or+ elevated Alk.PO in
TRANS the absence of other
CPK
LD
abn. Liver function tests
(AST,ALT)
 LIVER ENZYMES :
LD in Other Liver Diseases
Total LD + alkaline Phosphatase:
= space occupying lesions (e.g.)
 metastatic carcinoma
1o hepatocellular carcinoma
Hemangioma (rarely)

Source of LD (LD5) : ?
hepatocytes
tumor
both
 ALKALINE PHOSPHATASE
Distribution:
liver *
Bulk *
Bone *
kidney
ALP
intestine ALP
placenta ALP
Each of w/c
ALP
contain distinct
isoenzymes ALP
 ALKALINE PHOSPHATASE
Canalicular membrane
Func.: facilitate transfer of metabolites
across cell membranes ;lipid transport,
& calcification process in bone
synthesis

Liver:
exists predominantly in
biliary tract
a marker for biliary
dysfunction

R.V.=20-105 U/L (adults)

 ALKALINE PHOSPHATASE
Clinical Application
Obstruction of BT from:
Stones in duct
Infections
SOL
ALP (> 10 x ULN)
Reason for Increase:
Synthesis +
excretion of ALP
ALKALINE PHOSPHATASE
hepatocellular disease (due to
inflam/necrosis of the ductular
lining cells)
Obst.Cholestasis (2x
ULN,paralleling the rise of bili. )
Partial obst. Inc. ALP & normal
bili (dissociated jaundice)
CPC,liver-mod.elevated
SOL of liver

Clinical application
Conditions in Which the Serum ALP is

Hepatobiliary Bone Ds Other Conditions

Ds
Obstructive Osteitis deformans Healing fractures
jaundice
Biliary cirhosis Rickets Normal growth
Intrahep Osteomalacia Pregnancy
cholestasis
SOL(granuloma,abs Hyperthyroidism Note: dec. ALP is
cess seen in malnutrition
,metastatic ca)

Viral hepatitis Metastatic bone ds hypophosphotasia

Cirrhosis Osteogenic Sa
  GLUTAMYL TRANSFERASE
(GGT)
Tissue distribution:
Kidney
Pancreas
Liver
Prostrate
GGT
Ref.values:
3-35 U/L GGT
3-30 U/L GGT
GGT
 GLUTAMYL TRANSFERASE
(GGT)
> 10x ULN in chronic cholestasis due to primary
biliary cirrhosis or sclerosing cholangitis.
> Inc. in 60-70% ---alcohol abuse;
> most sensitive enzyme to determine liver
damage from alcohol abuse
> inc. in obst. disorders, SOL in the liver than w/
liver inj.
> obese ;
> high conc.of therapeutic drugs
(acetaminophen,carbamazepine, Dilantine)
Regulates the transport of a.a. across cell
membranes by catalyzing the transfer of a
glutamyl gr.from glutathione
  GLUTAMYL TRANSFERASE
(GGT)
Increased Activity:
Application:
Detecting Alcoholic Liver Ds
Liver metastasis in
anicteric patient
Chronic obstruction of bile
duct
 PROTEINS IN LIVER FUNCTION
Total serum protein
Composed of :
Albumin
Globulins (1,2, , immuno globulins)
A/G ratio is 2:1 ; a reversal ratio favors
renal / liver prob & chronic infect.
Ref. Range: 6-7.8 g/dL
(60% is albumin, 3.5-5 g/dL)
 PROTEINS IN LIVER FUNCTION
ALBUMIN
Functions:
Major osmotically active component of
vascular system
Transport protein( e.g. for bilirubin &
thyroid hormone)
Synthesized by liver at 120 mg/kg/day
 Hepatitis : total protein and albumin are
w/in their normal range
 Fulminant hep : abnormally
 Cirrhosis : low

 Albumin together with PT are better

indices of severity and prognosis of liver
disease
Other Causes of dec. TP and ALB.
 Renal disease
 Protein losing enteropathy
 Malnutrition
 Chronic inflammatory diseases
 Severe burn
An inc. in protein –Dehydration
 BILIRUBIN METABOLISM
Senescent rbc’s
RES Amino acid
Heme Globin
pool
RES
Iron + Protoporhyrin
Heme oxygenase
Albumin
Biliverdin
Recycled into new rbc’s
Bilirubin reductase
Liver Unconjugated + Albumin
bilirubin
2%-5% renal
excretion
Bilirubin glucoronide
Bilirubin uridine diphosphate
Glucoronyl transferase Bile
Small intestine
Alkal;ine pH + β-glucoronidase
Unconjugated bilirubin
Intestinal bacteria 20%
reabosrobed
Urobilinogen

Urobilin (fecal pigment)

DISORDERS OF BILE PIGMENT METABOLISM
Reference values:
T serum bilirubin (A): 0.1 - 1 mg/dL (1.7 to
17 umol/L)
Congugated Bilirubin (Direct):
0.3 mg/dL(5 umol/L)
Unconjugated Bilirubin (Indirect):
T Bilirubin – Conjugated Bilirubin
 BILIRUBIN

Serum / plasma , fasting state;shld.be tested

ASAP
Interference factors:
Hemolysis- false dec
lipemic – false inc
light – false dec.
 DISORDERS OF BILE
PIGMENT METABOLISM
JAUNDICE/ICTERUS
Bilirubin deposition in sclera
and in skin
> 2.5 mg/dL (43 umol/L)
 DISORDERS OF BILE PIGMENT METAB
(HYPERBILIRUBINEMIA)
Unconjugated
Excess Bilirubin Prodxn Impaired Bili Conjugation
Hemolytic Anemia  Physiologic jaundice of NB
Resorption of blood from  Breast milk jaundice
internal hge  Genetic Def. Of bili UGT
Ineffective erythropoiesis (Criggler-Najar)
(e.g.pernicious An,
 Gilbert syndrome
thalassemia
 Diffuse Hepatocelular Ds
Hepatic uptake
 Drug interference
 Some cases of Gilbert
syndrome
 DISORDERS OF BILE PIGMENT METAB
(HYPERBILIRUBINEMIA)
Conjugated
Dec. hepatic excretion of Bili Glucuronides
Deficiency in canalicular membrane
transporters
(Dubin-Johnson syndrome, Rotor
syndrome)
In extrahepatic obst.,total bili rarely exceeds 25
ug/dl
Ammonia
 Derived mainly from a.a. & nucleic acid
metabolism
 Metabolized only in the liver
 Px preparation: fasting,plasma, arterial
 good venipuncture technique,no fist
clenching
 R.V. 19- 16 ug/dl
Alpha-feto protein
 An onco-fetal protein
 Marker of differentiation
 Synthesized by fetal yolk sac, hepatocytes
 Detectable during 4th wks. of pregnancy
 Increased in :
HCC , benign liver ds ( cirrhosis )
Testicular Tumors (embryonal &yolk sac)
 Maybe inc. in breast,bronchial and colorectal Ca
 Ref.value : < 20ng/ml
> 400 ng/dl =HCC
 Inc. neural tube defect
6 Fundamental Patterns of Liver Function Tests
CONDITION AST ALT LD ALP TP ALB BIL NH4

1 H H H H N N H N

2 N N N N-sl L L H H
H
3 N N N H N N N-H N

4 N or N or H H N N N- N
H H H
5 sl H sl H sl H N- N N N- N
sl H SlH
6 Very H H H L L H H
H
 The end

Good clinical history

Complete P.E.