LIVER FUNCTION TESTS AND HOW

TO RELATE THEM TO DISEASES

Dr.Balakrishna
 INTRODUCTION
LFTs are a set of basic investigations
done in all suspected hepatobiliary
diseases.
They should be interpreted with the
background of clinical history and
physical findings to yield meaningful
conclusions.
No single test alone is sufficient to
provide complete estimate of the
function of liver.
 CLASSIFICATION
1) Tests of biochemical activity

a) Tests of liver cell injury

Alanine aminotransferase (ALT/SGPT)
Aspartate aminotransferase
(AST/SGOT)
Lactate dehydrogenase (LDH)
b) Tests of cholestasis
Alkaline phosphatase
Gamma glutamyl transferase
5-Nucleotidase
Bilirubin (total,conjugated,delta)
Urine urobilinogen
Serum and urine bile acids
2) Tests of liver synthetic capacity
Albumin and other proteins
Prothrombin time
Ammonia
Plasma and urine aminoacids
Serum lipid profile
3) Tests of quantitative function
Galactose elimination Test
Breath tests
MEGX test
4) Imaging studies
Ultrasound scan
CT scan
MRI scan
Radioisotope scan
5) Histologic studies

6) Specific serum tests

Ceruloplasmin
Alpha 1 antitrypsin
Alpha fetoprotein
7) Miscellaneous investigations
Bone marrow aspiration
Metabolic investigations
Skin biopsy
Genetic tests
Endoscopic tests
EEG
Ophthalmologic investigations
Molecular biology
 TRANSAMINASES
The two enzymes which are
sensitive
indicators of hepatocellular damage
are
1)AST/SGOT
2)ALT/SGPT
They are released in to circulation
by
hepatocellular necrosis
 AST is a mitochondrial and cytosolic
enzyme present not only in liver but also in
heart, skeletal muscle, brain, pancreas, lung,
RBC and kidney. Hence whenever these tissues
are acutely damaged, AST will be increased. It
has a long serum half life of 48 hrs.
ALT is a cytosolic enzyme seen mainly in
hepatocytes and has a shorter half life of 18
hrs.
Hence an increased ALT is more specific
and sensitive for hepatocellular injury
than AST.
 AST is relatively more specific for
chronic liver disease and
alcoholic liver disease and ALT for
acute liver disease.
De Ritis ratio: In alcoholic hepatitis,
the SGOT:SGPT ratio is always 2:1.
The ratio is usually <1 in patients
with acute and chronic nonalcoholic
hepatitis.
 Maximum levels of transaminases
are seen in conditions causing
extensive hepatocellular necrosis like
drug induced hepatitis, viral
hepatitis, ischaemic hepatitis, toxic
hepatitis.
In acute hepatitis, Transaminases are
10 times above normal. In chronic
hepatitis and cholestatic jaundice
they are about 5 times the normal
 Fluctuating levels of transaminases may be
seen in hepatitis C infection (yo-yo
phenomenon)
A sudden fall in transaminases in a sick
jaundiced patient is indicative of bad
prognosis as seen in acute fulminant hepatitis.
In anicteric hepatitis and inapparent hepatitis
the only biochemical abnormality may be an
elevated ALT or AST, which may be useful in
epidemiologic screening studies.
 Hemodynamic changes like diarrhoea and
vomiting may lead to small transient elevation of
transaminases which may confuse the clinician.
Unexpectedly elevated transaminases may be
seen in Obesity
Diabetes mellitus
Alpha 1 antitrypsin deficiency
Asymtomatic chronic hepatitis B and
C
Wilsons disease
 Diagnostic value of transaminases
The first laboratory abnormality detected in
early phase of viral hepatitis is elevated
transaminases.
In hepatitis, elevation of transaminases
precedes that of bilirubin by about one week.
Thus transaminases may be declining as serum
bilirubin is increasing in uncomplicated hepatitis.
During recovery phase of viral hepatitis, there is
a steady fall in level of transaminases.
Secondary elevation of
transaminases or their persistent
elevation indicates recrudesence of
hepatitis or development of chronic
hepatitis.
Absolute elevation is of little
prognostic value in predicting the
outcome of acute hepatitis
 ALKALINE
PHOSPHATASE
Serum alkaline phosphatase (AP) activity refers
to group of isoenzymes that hydrolyses organic
phosphate esters at alkaline pH to inorganic
phosphate and an organic radical.
Sources of AP
Liver - canalicular membrane
Bone - osteoblasts
Small intestine - brush border of enterocytes
Kidney - proximal convoluted tubules
Leukoytes
Placenta
 Bone isoenzyme is heat labile compared
hepatic AP which is relatively heat stable.
They can also be differentiated by
polyacrylamide gel electrophoresis.
The most practical method to decide
whether a high serum AP is due to liver
disease is by measuring another enzyme
which rises in cholestatic disease and that
is more specific to liver like GGT or 5-
Nucleotidase.
Zinc is a cofactor for AP and in condition
causing zinc deficiency, AP may be
reduced.
 Mechanisms that contribute to raised levels
of AP are 1) regurgitation from hepatocytes
2) increased synthesis

Dissociated jaundice In incomplete

biliary obstruction or when intrahepatic
obstruction is only partial, bilirubin may be
normal or only slightly elevated while AP is
quite high.This is seen in space occupying
lesions like metastasis.
 Diagnostic value of AP
serum AP is elevated in following conditions
1)elevated 5 times above normal in
cholestasis both intrahepatic and
extrahepatic.
2)lesser degrees of elevation, up to 3 times
the
normal are seen in all types of liver
disorders.
3) moderate elevation of AP of hepatic
origin
may be seen in disorders that do
not directly
involve liver like a) stage I & II of
hodgkin
disease b) myeloid metaplasia c)
CCF
d) intraabdominal infection.
4) genetic certain families have
 Bone AP is high in growing children,
also in
rickets, osteomalacia and
osteogenic deposits
of bone.

Normal value: 3-13 king angstrom

units/dl
up to 100 IU/l
 GAMMA GLUTAMYL
TRANSFERASE
It is synthesized by epithelium of small
bile ductules and hepatocytes.
This is one of the most sensitive tests for
presence of hepatobiliary disease and
similarly absence of raised GGT correlates
well with absence of hepatic metastasis.
GGT levels are higher in biliary tract
disease and cholestasis than in
hepatocellular disease.
 An elevated GGT is used to confirm that a
raised AP is of hepatobiliary origin. Hence it
is a more sensitive marker compared to AP.
The following drugs may elevate GGT raising
the false positive diagnosis of hepatobiliary
disease
1) anticonvulsants like phenytoin,
barbiturates & valproate. 2) TCA 3)
anticoagulants like warfarin 4)
antihyperlipidemics 5) OC pills 6) analgesics.
 An isolated raise in GGT is an early
indicator of alcohol consumption in
otherwise healthy children.
Cholestatic disease with normal GGT
are seen in 1) PFIC type I & II
2) Benign reccurent intrahepatic
cholestasis
Normal value: 0 - 60 IU/L
 5 - NUCLEOTIDASE
This enzyme is found in liver, intestine,
heart, blood vessel & endocrine pancreas.
In liver, this enzyme is isolated in both
sinusoidal and canalicular plasma
membrane.
It is elevated in hepatobiliary disease and
pregnancy but not in bone disease.
If it is elevated along with AP it can be
concluded that AP is that of hepatic origin.
Type of Transaminas Alkaline
jaundice es phosphatas
e
Hemolytic normal normal
jaundice
Hepatocellula >10 times <3 times
r jaundice elevated elevated
Cholestatic <5 times >3 times
jaundice elevated elevated
 SERUM BILIRUBIN
Bilirubin, a tetrapyrrole pigment, is a
breakdown product of ferroportoporphyrin
IX.
Its level confirms jaundice, indicates the
depth and used to assess the prognosis.
Its level represents the balance between
input from production and hepatic removal
of the pigment.
Unconjugated hyperbilirubinemia is due to
overproduction or impaired uptake or
conjugation of bilirubin.
 Conjugated hyperbilirubinemia is due to
decreased excretion or backward leakage
of the pigment.
Serum bilirubin (S.Bb) is not a sensitive
indicator of hepatic dysfunction and may
not accurately reflect the degree of liver
damage because an increase in Serum
albumin may induce a temporary shift of
bilirubin from tissue sites in to circulation.
 Many labs still use spectophotometry to
measure S.Bb as direct or indirect fractions.
This is based on Vandenbergh reaction where
Bb reacts with Ehrlichs diazotised sulfanilic
acid to produce chromogenic compounds
that can be detected colorimetrically.
Vandenbergh reaction (VR) can be used to
differentiate between direct and indirect Bb
because of different solubility properties of
two pigments.
 In Direct VR, reaction is carried out in aqueous
medium, the water soluble conjugated Bb
reacts to gives direct reaction.
In Indirect VR, reaction is carried out in
methanol. The intramolecular hydrogen bonds
of unconjugated Bb are broken and both
conjugated and unconjugated Bb react giving a
measure of total Bb level.
In this method, delta Bb is not detected as
separate entity and is included in the direct
fractionation.
 HPLC helps to accurately estimate
conjugated, unconjugated and delta
Bb.
Normal S.Bb value: 0.1 - 1 mg %.
If congugated fraction is >15 - 20 %
of total Bb, patient has congugated
hyperbilirubinemia and if
unconjugated Bb is >90%, patient
has unconjugated
hyperbilirubinemia.
properties Unconjugate Conjugated
d Bb Bb
Water insoluble soluble
solubility
Lipid solubility soluble insoluble

Vandenbergh indirect direct

reaction
Binding to ++++ +
albumin
 URINE UROBILINOGEN
UBG is formed in terminal ileum and colon
from conjugated Bb by Clostridium ramosum,
helped by E.coli.
UBG excreted in stool is called
stercobilinogen. It is converted by colonic
bacteria to stercobilin which imparts the
normal brown colour of stools. Hence in
cholestatic jaundice stools are pale as Bb can
not reach the gut and hence stercobilin is not
formed.
About 20% of UBG is reabsorbed and
undergoes enterohepatic circulation.
 Increase in UBG in urine is found in
hepatitis as damaged hepatocytes are not
able to reexcrete the UBG absorbed from
gut. It is thus a good index of
hepatocellular dysfunction, often when
other tests are normal.
Urine UBG is increased in following
conditions 1)hepatitis 2)malignant disease
of liver 3)cirrhosis 4)hemolytic anaemia
5)circulatory failure 6)pyrexia 7)severe
constipation.
 UBG is absent in following conditions
1)complete biliary obstruction
2)severe bilirubin glucoronyl
transferase
deficiency as seen in CN syndrome
type I.
3)severe diarrhoea
4)prolonged antimicrobial treatment
URINE ABNORMALITIES IN JAUNDICE

Type of Urine Urine

jaundice bilirubin urobilinog
en
Hemolytic nil +++
jaundice
Hepatocellul +++ +++
ar jaundice
Cholestatic +++ nil
jaundice
 ALBUMIN AND OTHER PROTEINS

Hepatocytes manufacture a number of

proteins, which are released in to plasma like
albumin, fibrinogen, alpha 1 antitrypsin,
haptoglobin, ceruloplasmin, transferrin,
prothrombin etc. Hence reduced levels of
these reflect a decline in synthetic capacity of
liver.
Of these, ceruloplasmin,fibrinogen,alpha 1
antitrypsin and haptoglobin are acute phase
reactants. Their serum levels may be raised
when the patient has acute hepatitis.
 The normal serum albumin is about 3.5 - 5 g%.
In liver disease, the fall in S.albumin
concentration is slow, as the serum half life of
albumin is about 22 days. Hence, a low albumin
is taken as a sign of chronic liver disease, rather
than acute disease.
A low S.albumin is seen in many non hepatic
disorders like nephrotic syndrome, PEM and
protein losing enteropathy. Nevertheless,
hypoalbuminemia is a excellent indicator of
severity of chronic liver disease.
 SERUM GLOBULINS
Serum IG are produced by stimulated
B-lymphocytes hence they do not
directly test liver function.
In chronic liver disease, the function
of reticuloendothelial cells of liver is
impaired. Hence bacteria can not be
destroyed and they reach the
circulation, stimulating the B-
lymphocytes to produce IG.
 The gamma globulin level is increased in
cirrhosis due to increased production. The
increased number of plasma cells in bone
marrow may be the source.
Elevation of specific IG
- IgG in chronic active hepatitis and
cryptogenic cirrhosis.
- IgM is markedly elevated in primary biliary
cirrhosis and to some extent in chronic active
hepatitis and cryptogenic cirrhosis
- IgA is markedly elevated in alcoholic
cirrhosis and to some extent in cryptogenic
cirrhosis and primary biliary cirrhosis.
 BILE ACIDS
The liver is the only organ that can
synthesize bile acids.
The primary bile acids, cholic acid and
cheno deoxycholic acid are formed from
cholesterol. Their synthesis is regulated by
amount of bile acids returning to liver in
enterohepatic circulation.
The colonic bacteria convert primary bile
acids to secondary bile acids, mainly
deoxycholic acid and a very little
lithocholic acid, by 7 alpha
dehydroxylation.
 Tertiary bile acids like ursodeoxy cholic
acid are produced in liver by epimerization
of secondary bile acids.
The bile acids are conjugated in liver with
the aminoacids glycine and taurine. This
prevents reabsorption in biliary tree and
small intestine but permits conservation by
absorption in terminal ileum.
The absorbed bile salts enter the portal
venous system and reach the liver where
they are taken up actively by hepatocytes.
 The bile salts are reconjugated and
excreted in bile. This entero hepatic
transport of bile salts takes place 2-15
times per day, which helps to prevent
the loss of bile salts.
The maintenance of normal S.bileacids
depends on hepatic blood flow, hepatic
uptake, secretion of bile acids by liver
and entero hepatic circulation.
 Serum bile acids can be determined by
3 methods
1)Gas liquid chromatography
2)Enzymatic assays
3)Radioimmunoassay
S.bileacids measured by
Radioimmunoassy may be the best
screening test for liver disease.
Elevation of S.bileacids is specific for
hepatobiliary disease.
 The sensitivity of S.bileacid estimation is
less specific for detecting hepatocellular
damage in viral hepatitis or chronic liver
disease.
However, it is better than S.albumin or
Prothrombin time because the value
depends not only on hepatic damage but
also on excretory function and portal
venous shunting. It may be useful in
determining the prognosis.
 PROTHROMBIN TIME
Liver plays 3 roles in control of coagulation:
1) Production clotting factors except von
Willebrand factor, which is synthesized in
megakaryocytes and vascular endothelial
cells.
2) Clearance of activated factors from
circulation.
3) Production and breakdown of all factors
integral to fibrinolysis like plasminogen and
plasminogen activator.
 PT is measure of time it takes for
prothrombin to be converted to thrombin in
the presence of tissue extract, calcium ions
and activated factors V, VII,X.
The result of reaction that produced
thrombin is expressed in seconds or as a
ratio of plasma PT to a control PT.
Normal values are 12-13 seconds.
Prolongation of more than 2 sec is
considered pathologic and values >3 sec
above normal indicate risk of bleeding.
 Activated factor VII is the key enzyme
of extrinsic pathway as it has shortest
halflife. Patient with early liver
disease may present with an isolated
prolonged PT.
A prolonged PT also suggests a poor
prognosis in chronic liver disease, this
along with decreasing serum albumin
is the most important parameter to
decide on liver transplantation
 In a patient with liver disease PT may also
prolonged due to non hepatic causes other
than vitamin K deficiency like DIC.
Factor VIII is also synthesized from non
hepatic sources like vascular endothelium
hence its level is usually normal in liver
disease, unless it is being consumed as in DIC.
Thus factor VIII level may help to differentiate
hemorrhage due to severe liver disease alone
from that due to accompanying DIC.
 INTERNATIONAL NORMALIZATION RATIO
(INR)
This system standardizes the PT for different
thromboplastin reagents thus providing a universal
standard by which to compare any given lab result
with that of WHO standard.

ISI
INR = (patients PT / normal PT)
ISI = International sensitization index (provided
with each batch of thromboplastin reagent)
Liver biopsy is contraindicated if INR is >1.3
INR helps to monitor patients on warfarin therapy
 Advantages of using INR system
1)Easier, smoother regulation of anti -
coagulation.
2)Travelling patients will have a standard,
regardless of lab used.
3)Standardization of laboratory and
research efforts.
4)Reduced risks of complications associated
with higher doses of anticoagulants.
 USES OF PT
1)It helps to differentiate cholestatic from
hepatocellular jaundice.
2)It is not a sensitive index of liver disease,
as even with severe form of cirrhosis, it
may be normal or slightly prolonged.
3)It is of high prognostic value especially in
acute hepatocellular jaundice.
4)A prolonged PT is not specific for liver
disease as it may be seen in congenital
deficiencies of coagulation factors and also
in acute conditions like DIC and ingestion
of drugs that effect prothombin complex.
 SERUM AMMONIA
The concentration of ammonia in blood is
regulated by balance of its production and
clearence.
It is produced in colon by action of bacterial urease
on dietary proteins and aminoacids.
Ammonia is converted by liver in to urea and then
into glutamine by urea cycle.
The liver removes 80% of portal venous ammonia
in a single pass.
In chronic liver disease and portal hypertension
,large amounts of ammonia bypass liver and reach
brain, contributing to hepatic encephalopathy.
However s.ammonia and level of hepatic
encephalopathy have a poor correlation.
 PLASMA AND URINE
AMINOACIDS
Several IEM manifest as hepatomegaly with
or with out evidence of hepatocellular injury
or cholestasis. These include Heriditary
tyrosinemia, Urea cycle disorders and
methylmelanic aciduria.
Elevated levels of methionine , phenylalanine
and tyrosine may be seen in patients with
significant hepatocellular disease of any
cause as well as in specific heriditary
disorders like wilsons disease, galactosemia,
heriditary fructose intolerance.
 SERUM LIPIDS AND
LIPOPROTEINS
Lipids and lipoproteins are mainly synthesized
in liver except chylomicrons, which are
synthesized in intestine.
Liver diseases significantly affect serum lipids
and lipoprotein levels.
Serum cholesterol is increased in cholestatic
jaundice. Skin xanthomas develop if elevated
5 times above normal.
An abnormal lipoprotein, Lipoprotein X is
synesized in biliary atresia and neonatal
hepatitis. Following cholestyramine therapy,
level decreases in neonatal hepatitis, where as
continues to be high in biliary atresia.
 SEROLOGICAL TESTS
Hepatitis A is diagnosed by an elevated IgM anti
HAV.
The best serological test to diagnose acute
hepatitis B is IgM anticore antibody, since HBsAg
will be positive in asymtomatic carriers also.
Hepatitis C is diagnosed by recombinant
immunoblot assay II (RIBA-II) to detect
antibodies against C100-3,5-1-1,C22 or C33
antigens. It is confirmed by HCV RNA by PCR.
IgM anti D and IgM anti HEV help to diagnose
HDV and HEV.
 Serological markers in
Hepatitis B
HBsAg HBeAg Anti HBe Anti HBc Anti HBs significan
ce
positive positive negative IgM negative Acute
HB,highly
infectious
positive positive negative IgG negative Chr.HB/car
rier,highly
infectious
Positive negative Negative/p IgG negative Chr.HB/car
ositive rier, less
infectious

negative negative Negative/p IgM negative Window

ositive period,
infectious
negative negative negative IgG positive Immunity
following
HB
vaccinatio
TESTS OF QUANTITATIVE FUNCTION

These tests are complex and are done

only in research labs. These include
1)Galactose elimination test -
galactose is taken up by liver and
converted to galactose I phosphate by
glactokinase, which is the rate limiting
reaction in galactose elimination from
blood. Galactokinase activity depends
on functional liver mass. Hence
galactose elimination gives an estimate
of functional hepatic cell mass.
2)Breath test Aminopyrine labelled
with c14 is given orally. It is
metabolised by cytochrome p-450
dependent demethylation to co2 in
only liver. samples of 14co2 are
collected from the mouth for 2 hrs.
The expired 14co2 correlates with
rate of disappearence of radioactivity
from plasma. The test reflects the
residual functional microsomal mass
and viable hepatic tissue.
3)MonoEthylGlycineXylinide test (MEGX
Test) - MEGX is the main metabolite of
Lignocaine formed in hepatocyte microsomes
by cytochrome p450dependent
demethylation. Lignocaine is given IV and
serum MEGX is measured at 15 min and 30
min. Its level is decreased in cirrhosis
compared to control. MEGX test is useful to
assess the quality of organ donors. It is much
superior to conventional LFT in predicting
graft survival.
 RADIOLOGY
PLAIN RADIOGRAPH OF ABDOMEN - It
will give an indication of size of liver and
spleen. However it is rarely of diagnostic
value and hence not used frequently.
ULTRASONOGRAPHY OF ABDOMEN - It
provides information about size of liver,
spleen, pancreas, kidney and gallbladder. It
detects gall stones, tumors, hemangiomas,
abscess and cysts with in liver. It allows
targeting of lesions for liver biopsy.
 A small or absent gallbladder after
fasting suggest either severe intrahepatic
cholestasis or biliary atresia in a neonate.
An enlarged gallbladder may suggest
primary sclerosing cholangitis.
CT SCAN it is helpful for detection and
biopsy of hepatic tumors and space
occupying lesions. IV contrast causes
enhancement of vascular lesions and wall
of abscesses and helps in differentiation
of tumors from other solid masses.
 ERCP - A fibreoptic duodenoscope is
passed in to 1st part of duodenum, ampulla
of vater is identified, the pancreatic and
biliary ducts are cannulated and contrast
is injected. This is very useful in evaluation
of extrahepatic liver disease in older
children like choledochal cysts, PSC and
chronic pancreatitis. It is technically very
difficult in neonatal cholestsis.
It can also be used to remove CBD stones
and for insertion of biliary stents.
 Percutaneous Transhepatic
Cholangiography (PTC) - It is useful for
identification of biliary disease, if
intrahepatic bileducts are dilated secondary
to obstruction and ERCP is impossible or
unsuccessful. A thin needle (Chiba needle)
is passed through liver, the bile ducts or
gallbladder is punctured and radiological
contrast is injected. External drainage of
biliary tree, dilatation of biliary strictures
and the introduction of biliary stents are all
possible using this procedure.
 Hepatobiliary Scintigraphy
-The development of soluble radioisotopes
(technicium trimethyl I bromo iminodiaceic
acid) which are taken up well by hepatocytes
despite elevated Bb levels have been utilized
to either hepatic uptake or biliary excretion.
-Pretreatment with phenobarbitone
(5mg/kg) for 3-5 days prior to investigation
improves hepatic uptake of isotope.
-It is most useful in assessment of biliary excretion
in DD of neonatal cholestasis. Under normal
conditions biliary excretion is completed in 4 hrs.
-Delayed excretion or no excretion after 24hrs
suggests severe intrahepatic cholestasis or EHBA.
-It is of some value in diagnosis of hepatic vein
obstruction (Budd Chiari syndrome) as poor uptake
of liver is demonstrated in most of liver except in
caudate lobe which has got separate venous
drainage.
 ANGIOGRAPHY Visualisation of coeliac
axis, hepatic and splenic blood vessels is
obtained by femoral artery catheterization
and injection of radiological contrast. This
techniqhe has 2 parts.
-Arterial phase, which provides information
about coeliac axis, hepatic and splenic artery
abnormalities, vascularization and anatomy
of hepatic tumors, hepatic hemangiomas or
detection of hepatic artery thrombosis.
-Venous phase, provides
information about patency of portal,
splenic and superior meseteric veins
and the presence of portal
hypertension and identification of
mesenteric, esophageal or gastric
varices.
-Femoral artery spasm or
thrombosis is an occasional side
effect, but rarely requires operative
 Splenoportography here splenic and portal
radicles are visualised by injection of contrast
into spleen, it has largely been replaced by
hepatic angiography.
MRI It has now replaced hepatic angiography
as best way to stage or diagnose hepatic
tumors and to identify their vascular supply.
-It may provide valuable information about
liver or brain consistency and storage of heavy
metals.
The recent development of MRCP, in
which both intra and extrahepatic
biliary ducts, and also the pancreatic
duct may be detected, may replace
ERCP as a diagnostic investigation.
 LIVER BIOPSY
The diagnosis of most liver diseases
requires histological confirmation and
thus liver biopsies are a routine
procedure in specialist centres.
Indications
unexplained hepatomegaly
unexplained jaundice
unexplained elevation of liver
enzymes
cholestatic liver disease biliary
atresia and neonatal hepatitis
cirrhosis
chronic hepatitis
drug related hepatitis
infections of liver like TB
enzyme analysis for IEM
copper estimation in wilson disease
when other tests are equivocal
post liver transplantation to assess
acute rejection.
 Contraindications
PT >3sec or prolonged or INR >1.3
thrombocytopenia - PLC <60,000
presence of grossly dilated bile ducts
angiomatous malformations of liver
hydatid cysts
severe ascites
Liver biopsy is performed by 3 routes
Percutaneous route :
Transthorasic/subcoastal
Transvenous route
By laparoscopy
 Complications
hemorrhage
intrahepatic hematoma
hemobilia
pleurisy and perihepatitis
development of AV fisthula
biliary peritonitis
puncture of other organs
infection
 As the morphologic features of specific
liver disease are distinctive, liver biopsy
enables us to make an etiological
diagnosis. Thus it helps to diagnose
chronic hepatitis, cirrhosis, neonatal
cholestasis, hepatic fibrosis etc.
Peroxidase positive diastase resistant
magenta coloured granules in periportal
hepatocytes are suggestive of alpha 1
antitrypsin deficiency.
 In Dubin Jhonson syndrome, the
macroscopic liver is hyperpigmented and
microscopy shows deposition of lipofuscin
and melanin (black liver jaundice).
The normal liver copper is up to 55mcg/g of
dry liver tissue and is very high in ICC and
wilsons disease.
Liver biopsy helps to diagnose IEM like
Galactosemia by quantitating the enzyme
content of liver
 METABOLIC INVESTIGATIONS
Many IEM like galactosemia, heriditary
fructose intolerance, alpha 1 antitrypsin
deficiency etc present with hepatomegaly
and jaundice, so it is essential to screen
for these diseases as a part of
investigation of liver disease in neonates
and older children.
BONEMARROW ASPIRATION
It is performed in babies with undiagnosed
neonatal hepatitis with
hepatpsplenomegaly to exclude Niemann
pick disease or Gaucher disease or at any
age if storage disorder is suspected.
 SKIN BIOPSY
It helps in diagnosis of IEM like Niemann
pick disease A,B or C or Tyrosinemia type 1.
GENETIC TESTS
For diagnosis of genetic diseases, samples
for DNA analysis and chromosomes for
both child and parent may be necessary.
ENDOSCOPY
upper GI endoscopy to diagnose peptic
ulcer disease or esophageal or gastric
varices secondary to portal hypertension.
 NEUROPHYSIOLOGY
EEG is mostly used in assessment of
hepatic encephalopathy.
OPHTHALMOLOGY
Kayser Fleischer rings in Wilson disease
posterior embryotoxon or optic drusen
in Alagille syndrome
Oil drop cataract in Galactosemia
Cherry red spot in Niemann pick disease
typeA
 MOLECULAR BIOLOGY
Progress in identifying specific genes
and DNA sequencing has made
possible the diagnosis of many IEM
and inherited disease and led to
identification of mitochondrial
disorders.
-Gene cloning and molecular cloning
methods help to identify viruses like
hepatitis C and G.
THANKYOU