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Symposium : Newer Diagnostic Tests

Liver Function Tests and their Interpretation

B.R. Thapa and Anuj Walia

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Post Graduate Institute of Medical Education and
Research, Chandigarh

ABSTRACT
Liver function tests (LFT) are a helpful screening tool, which are an effective modality to detect hepatic dysfunction. Since the liver performs a variety
of functions so no single test is sufficient to provide complete estimate of function of liver. Often clinicians are faced with reports that do not tally with
the clinical condition of the patient and they face difficulty in interpreting the LFT.
An attempt is being made to study and understand the LFT and simplify their interpretation with algorithms. [Indian J Pediatr 2007; 74 (7) : 663-671]
Email: brthapa1@yahoo.co.in

Key words : LFT; Alkaline phosphatase; Albumin; Prothrombin time; Aminotransferases (EVERYTHING
& AST)

Liver has to perform different kinds of biochemical, synthetic Assess severity : They are helpful to assess the severity and
and excretory functions, so no single biochemical test can predict the outcome of certain diseases like primary biliary
detect the global functions of liver. cirrhosis.
All laboratories usually employ a battery of tests for initial Follow up : They are helpful in the follow up of certain liver
detection and management of liver diseases and these tests diseases and also helpful in evaluating response to therapy like
are frequently termed “Liver function tests”, although they are autoimmune hepatitis.
of little value in assessing the liver function per se. In spite of
receiving a lot of criticism for this terminology, the phrase ‘Liver LIMITATIONS
function tests’ is firmly entrenched in the medical lexicon. It
might be argued that ‘Liver injury tests’ would be a more Lack sensitivity: The LFT may be normal in certain liver
appropriate terminology. Moreover, the clinical history and diseases like cirrhosis, non cirrhotic portal fibrosis, congenital
physical examination play important role to interpret the hepatic fibrosis, etc.
functions. The role of specific disease markers, radiological
imaging and liver biopsy can not be underestimated.1,2 Lack specificity : They lack specificity and are not specific for
any particular disease. Serum albumin may be decreased in
chronic disease and also in nephrotic syndrome.
Aminotransferases may be raised in cardiac diseases and
USES hepatic diseases.

Except for serum bile acids the LFT are not specific for liver
The various uses of Liver function tests include: diseases and all the parameters may be elevated for
pathological processes outside the liver.1,3
Screening : They are a non-invasive yet sensitive screening
modality for liver dysfunction. Thus, we see that LFT have certain advantages as well as
Pattern of disease : They are helpful to recognize the pattern limitations at the same time. Thus, it is important to view them
of liver disease. Like being helpful in differentiating between keeping the clinical profile of the patient in mind.
acute viral hepatitis and various cholestatic disorders and
chronic liver disease. (CLD).
CLASSIFICATION OF LIVER FUNCTION TESTS

A. Tests of the liver’s capacity to transport organic anions

Correspondence and Reprint requests : Prof. B.R. Thapa, Professor and Head and to metabolize drugs- Serum bilirubin, urine bilirubin,
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Post Graduate Institute urobilinogen etc.
of Medical Education and Research, Chandigarh 160012
B. Tests that detect injury to hepatocytes (serum enzyme
[Received August 10, 2006; Accepted August 11, 2006]
tests) – Aminotransferases, alkaline phosphatase, ã

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B.R.Thapa and A. Walia

glutamyl transpeptidase, 5 nucleotidase, leucine reacts in 30 minutes after addition of alcohol. Normal
aminopeptidase etc. range is 0.2-0.9 mg/dl (2-15µmol/L). It is slightly higher
by 3-4 µmol/L in males as compared to females. It is this
C. Tests of the Liver’s biosynthetic capacity- Serum
factor, which helps to diagnose Gilbert syndrome in
proteins, albumin, prealbumin, serum ceruloplasmin,
males easily.
procollagen III peptide, a 1 antitrypsin, a feto protein,
prothrombin time etc. ii. Direct Bilirubin : This is the water-soluble fraction.
This is measured by the reaction with diazotized
The clinical significance of LFT is given in Table 1
sulfanilic acid in 1 minute and this gives estimation of
A. Tests of the liver’s capacity to transport organic conjugated bilirubin. Normal range 0.3mg/dl( 5.1µmol/
anions and to metabolize drugs L)

iii. Indirect bilirubin: This fraction is calculated by the

1. SERUM BILIRUBIN difference of the total and direct bilirubin and is a
measure of unconjugated fraction of bilirubin.1,5
Bilirubin is an endogenous anion derived from The diazo method of bilirubin estimation is not very
hemoglobin degradation from the RBC. The classification accurate especially in detecting low levels of bilirubin.
of bilirubin into direct and indirect bilirubin are based on Direct bilirubin over estimates bilirubin esters at low
the original van der Bergh method of measuring bilirubin levels and under estimates them at high
bilirubin. Bilirubin is altered by exposure to light so concentration. Thus slight elevation of unconjugated
serum and plasma samples must be kept in dark before bilirubin not detected, which is of value in detecting
measurements are made. When the liver function tests
conditions like Gilbert syndrome.5
are abnormal and the serum bilirubin levels more than
17µmol/L suggest underlying liver disease.4 A newer highly accurate method of estimation
involves alkaline methanolysis of bilirubin followed by
Types of bilirubin chloroform extraction of bilirubin methyl esters and later
i. Total bilirubin: This is measured as the amount, which separation of these esters by chromatography and

TABLE 1. Clinical Significance of Liver Function Tests in Children

Normal Basis of Associated liver Extrahepatic

abnormality disease sources

Bilirubin 0-1mg/dl Decreased hepatic Mild elevations: Liver diseases, Hemolysis, ineffective
clearance physiological jaundice, inherited erythropoiesis, hematoma,
hyperbilirubinemias myoglobinemia
Moderate elevations: EHBA, IHBA, drugs,
viral hepatitis, inherited hyperbilirubinemias
Aminotransferases ALT Leakage from Marked elevations: Hepatitis, autoimmune, toxic, ALT specific for hepatocytic
10-55 U/L damaged tissues neonatal hepatitis, ischaemic necrosis. AST for skeletal,
AST 10-40 U/L AST/ALT >2 in CLD cardiac, muscle, kidney, brain.
AST/ALT <1 acute hepatitis/ injury

Alkaline phosphatase Overproduction and Mild elevations: Liver disease leakage Bone diseases, placenta,
45-115 U/L in blood Moderate elevations: EHBA, IHBA, intestine, tumour
infiltrating disorders, granulomatous
hepatitis

ÿ glutamyl transpeptidase Overproduction and Same as alkaline phosphatase, leakage Kidney, spleen,pancreas,
0-30 U/L in blood Raised in EHBA, PFIC heart, lung, brain
5- nucleotidase Overproduction and Same as alkaline phosphatase leakage Specific for liver
0-11 U/ml in blood
Prothrombin time Decreased synthetic Acute/chronic liver disease- non capacity Vit K deficiency secondary
10-14sec responsive to Vit K to MAS, PEM, DIC
EHBA/biliary obstruction- responsive
to Vit K

International normalized Decreased synthetic Same as PT Same as PT

ratio 0.9-1.2 capacity
Serum albumin Decreased synthesis CLD, cirrhosis Nephrotic syndrome, protein
3.5-5.5g/dl losing enteropathy, PEM,
IBD, malignancy

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Liver Function Tests and their Interpretation

spectrophotometric determination at 430 nm.1 Other causes of extreme hyperbilirubinemia include severe
parenchymal disease, septicemia and renal failure.5
a. Diagnostic value of bilirubin levels : Bilirubin in body
is a careful balance between production and removal of
the pigment in body. Hyperbilirubinemia seen in acute viral 2. URINE BILIRUBIN
hepatitis is directly proportional to the degree of histological
injury of hepatocytes and the longer course of the disease. The presence of urine bilirubin indicates hepatobiliary
disease. Unconjugated bilirubin is tightly bound to albumin
Hyperbilirubinemia: It results from overproduction / and not filtered by the glomerulus and thus not present in
impaired uptake, conjugation or excretion / regurgitation of urine. Measurable amounts of conjugated bilirubin in
unconjugated or conjugated bilirubin from hepatocytes to serum are found only in hepatobiliary disease.1
bile ducts.Approach to jaundice in neonatal period is given
in Fig 1. Because the renal threshold for conjugated bilirubin is
low and the laboratory methods can detect low levels of
S. Bilirubin > 2 mg/dl bilirubin in urine so conjugated bilirubin may be found in
urine when the serum bilirubin levels are normal. This is
the case in early acute viral hepatitis.1, 6
Conjugated Unconjugated Tests strips impregnated with diazo reagent are easy to
hyperbilirubinemia > hyperbilirubinemia > use and detect as little as 1-2µ mol bilirubin/L.5
20% of total 80% of total

3. UROBILINOGEN
Cholestasis

An increase in the urobilinogen in urine is a sensitive

Intrahepatic: Extrahepatic: indicator of hepatocellular dysfunction. It is a good
Neonatal hepatitis EHBA
IHBA Choledochal cyst
indication of alcoholic liver damage, well compensated
cirrhosis or malignant disease of the liver. In viral hepatitis
Fig. 1. Algorithm to Approach Hyperbilirubinemia in Neonatal it appears early in urine. It is markedly increased in
Period 5
hemolysis.3,

Increased unconjugated bilirubin: This results from In cholestatic jaundice urobilinogen disappears from
overproduction/impaired uptake, conjugation urine. It may be intermittently present in case of gallstones.3

Increased conjugated bilirubin: Impaired intrahepatic

excretion / regurgitation of unconjugated or conjugated Urobilinogen gives a purple reaction to Ehrlich’s
bilirubin from hepatocytes of bile ducts.4 aldehyde reagent. A dipstick containing this reagent allows
rough and ready quantification. Freshly voided urine should
Serum bilirubin could be lowered by drugs like be used.5
salicylates, sulphonamides, free fatty acids which displace
bilirubin from its attachment to plasma albumin. On the B. Tests that detect injury to hepatocytes( serum
contrary it could be elevated if the serum albumin increases enzyme tests) : The liver contains thousands of enzymes
and the bilirubin may shift from tissue sites to circulation.1 and these enzymes have no function and behave as serum proteins.

b. Prognostic value of bilirubin levels A. ENZYMES THAT DETECT HEPATOCELLULAR

NECROSIS – AMINOTRANSFERASES
Bilirubin may be of prognostic value in conditions like
fulminant hepatic failure where deep jaundice is associated
with increased mortality.2,4 The aminotransferases (formerly transaminases)are the
most frequently utilized and specific indicators of
Hyperbilirubinemia and Hemolysis hepatocellular necrosis. These enzymes- aspartate
Bilirubin itself is not soluble in water and is bound to aminotransferase(AST, formerly serum glutamate
albumin and thus does not appear in urine. Hemolysis with oxaloacetic transaminase-SGOT) and alanine amino
overproduction of bilirubin and concomitant reduced GFR transferase( ALT, formerly serum glutamic pyruvate
cause decreased excretion and can lead to high bilirubin transaminase-SGPT) catalyze the transfer of the á amino
levels.1 Bilirubin levels in excess of 25 mg/ dl may be seen acids of aspartate and alanine respectively to the á keto
in hemolysis in association with liver disease. 2,4 group of ketoglutaric acid. ALT is primarily localized to the
liver but the AST is present in a wide variety of tissues

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B.R.Thapa and A. Walia

like the heart, skeletal muscle, kidney, brain and liver. 4, 2 derived from the cytosolic isoenzyme.4,8
AST : alanine + ÿ ketoglutarate = oxaloacetate + Algorithm to approach mild and sustained rise of
glutamate aminotransferases is given in Fig. 2.
ALT: alanine + ÿ ketoglutarate = pyruvate + glutamate5 Large increases in mitochondrial AST occur in serum
after extensive tissue necrosis. Because of this, assay of
mitochondrial AST have been advocated in myocardial
Whereas the AST is present in both the mitochondria infarction. Mitochondrial AST is also increased in chronic
and cytosol of hepatocytes, ALT is localized to the liver disease. 9
cytosol.2,3 The cytosolic and mitochondrial forms of AST
are true isoenzymes and immunologically distinct.7 Their activity in serum at any moment reflects the
relative rate at which they enter and leave circulation. Of
About 80% of AST activity in human liver is contributed the numerous methods used for measuring their levels,
by the mitochondrial isoenzyme, whereas most of the the most specific method couples the formation of pyruvate
circulating AST activity in normal people is and oxaloacetate- the products of the

Elevated Aminotransferases

History and physical examination During infancy

Viral serology Metabolic work up for galactosemia,

tyrosinemia, fructosemia etc

Positive
Negative

USG Doppler, CT Symptoms or signs of liver

scan, MR angiography disease

Yes No

USG, Doppler, CT Presence of reversible causes like

scan, MR angiography drugs, obesity, NASH

No Yes

Wilson/Autoimmune/Hep AST/ALT return to normal after

B,C/alpha 1 antitrypsin intervention

USG, Doppler, CT, MR Observe

angiography

Fig. 2. Algorithm to Approach Mild but Sustained Rise of Aminotransferases

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Liver Function Tests and their Interpretation

aminotransferase reactions to their enzymatic reduction to lactate Mitochondrial AST: Total AST ratio : This ratio is
and malate. 10 characteristically elevated in alcoholic liver disease.
Abstinence from alcohol improves this ratio. It is also seen to be
Virtually no aminotransferases are present in the urine or bile
high in Wilson’s disease.4
and hepatic sinusoids are the primary site for their clearance. 11,
12 Falsely low aminotransferase levels : They have been seen in
patients on long term hemodialysis probably secondary to either
MILD, MODERATE AND SEVERE ELEVATIONS OF dialysate or pyridoxine deficiency.
AMINOTRANSFERASES Low levels have also been seen in uremia 15,16

Other enzymes tests of hepatocellular necrosis

1. Severe ( > 20 times, 1000 U/L) : The AST and ALT levels
None of these tests have proved to be useful in practice than the
are increased to some extent in almost all liver diseases. The
aminotransferases.These include glutamate dehydrogenase,
highest elevations occur in severe viral hepatitis, drug or toxin
isocitrate dehydrogenase, lactate dehydrogenase and sorbitol
induced hepatic necrosis and circulatory shock. Although enzyme
dehydrogenase
levels may reflect the extent of hepatocellular necrosis they do
not correlate with eventual outcome. In fact declining AST and b. Enzymes that detect cholestasis
ALT may indicate either recovery of poor prognosis in fulminant
hepatic failure.4, 5 1. ALKALINE PHOSPHATASE

2. Moderate (3-20 times): The AST and ALT are moderately Alkaline phosphatases are a family of zinc metaloenzymes, with
elevated in acute hepatitis, neonatal hepatitis, chronic hepatitis, a serine at the active center; they release inorganic phosphate
autoimmune hepatitis, drug induced hepatitis, alcoholic hepatitis from various organic orthophosphates and are present in nearly
and acute biliary tract obstructions. The ALT is usually more all tissues. In liver, alkaline phosphatase is found histochemically
frequently increased as compared to AST except in chronic liver in the microvilli of bile canaliculi and on the sinusoidal surface of
disease. In uncomplicated acute viral hepatitis, the very high hepatocytes. Alkaline phosphatase from the liver, bone and
initial levels approach normal levels within 5 weeks of onset of kidney are thought to be from the same gene but that from
illness and normal levels are obtained in 8 weeks in 75% of intestine and placenta are derived from different genes.5
cases. Approach to elevated alkaline phosphatase is given in Fig. 3.

For reasons, which are not, understood AST levels appear

disproportionately low in patients with Wilson disease.4,5 In liver two distinct forms of alkaline phosphatase are also
found but their precise roles are unknown. In healthy people
most circulating alkaline phosphatase originates from liver or
3. Mild (1-3 times) : These elevations are usually seen in sepsis bone.17
induced neonatal hepatitis, extrahepatic biliary atresia (EHBA),
fatty liver, cirrhosis, non alcoholic steato hepatitis(NASH), drug The internationally recommended reference method uses p-
toxicity, myositis, duchenne muscular dystrophy and even after nitrophenol phosphate as substrate, in al alkaline buffer. Fresh
vigorous exercise.1,4 unhemolysed serum is the specimen of choice for the estimation.
Heparinized plasma may also be used. The test should not be
One third to one half of healthy individuals with an isolated
done on plasma if citrate, oxalate or EDTA were used as
elevation of ALT on repeated testing have been found to be
normal.13 anticoagulants, they form a complex with zinc and the alkaline
phosphatase, causing irreversible enzyme inactivation.5
AST: ALT ratio

The ratio of AST to ALT is of use in Wilson disease, CLD and Average values of alkaline phosphatase vary with age and
alcoholic liver disease and a ratio of more than 2 is usually are relatively high in childhood and puberty and lower in middle
observed. The lack of ALT rise is probably due to pyridoxine age and higher again in old age. Males usually have higher
deficiency. In NASH the ratio is less than one in the absence of values as compared to females. The levels correlate with
fibrosis on liver biopsy.4 person’s weight and inversely with the height of person.
18

In viral hepatitis the ratio is usually less than one. The ratio
invariably rises to more than one as cirrhosis develops possibly Not uncommonly isolated elevated levels of alkaline
because of reduced plasma clearance of AST secondary to phosphatase in otherwise healthy persons return to normal on
19
impaired function of sinusoidal cells.14 follow up.

ALT exceeds AST in toxic hepatitis, viral hepatitis, Highest levels of alkaline phosphatase occur in cholestatic
chronic active hepatitis and cholestatic hepatitis
5
disorders. Elevations occur as a result of both

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B.R.Thapa and A. Walia

Elevated Alkaline phosphatase (AP)

History and physical examination

Repeat test while patient is fasting

Elevated Normal

GCT to confirm Observe

hepatic origin of AP

Elevated Normal

Evaluate for
Abdominal USG
extrahepatic source

Evidence of biliary No evidence of

obstruction biliary obstruction

HIDA scan, MRI, ERCP, 1. Metabolic workup- Liver MRCP,

MRCP, FNAC of mass, Galactosemia, ERCP
AFP, POC Tyrosinemia
2. TORCH Infections

Fig. 3. Algorithm to evaluate Marked Rise of Alkaline Phosphatase

intrahepatic and extrahepatic obstruction to bile flow and associated specifically with intrahepatic disease as
the degree of elevation does not help to distinguish opposed to extrahepatic obstruction.21
between the two. Alkaline phosphatase levels are likely
to be very high in EHBA.4 Hepatic and bony metastasis can also cause elevated
levels of alkaline phosphatase. Other diseases like
The mechanism by which alkaline phosphatase infiltrative liver diseases, abscesses, granulomatous liver
reaches the circulation is uncertain; leakage from the bile disease and amyloidosis may also cause a rise in alkaline
canaliculi into hepatic sinusoids may result from leaky phosphatase. Mildly elevated levels of alkaline
tight junctions. 5,20 and the other hypothesis is that the phosphatase may be seen in cirrhosis and hepatitis of
damaged liver fails to excrete alkaline phosphatase made congestive cardiac failure.5
in bone, intestine and liver. 1
Low levels of alkaline phosphatase occur in
In acute viral hepatitis, alkaline phosphatase is usually hypothyroidism, pernicious anemia, zinc deficiency and
either normal or moderately increased. Hepatitis A may congenital hypophosphatasia. 22 Wilson’s disease
present a cholestatic picture with marked and prolonged complicated by hemolysis and FHF may also have very
itching and elevation of alkaline phosphatase. Tumours low levels of alkaline phosphatase. Ratio of alkaline
may secrete alkaline phosphatase into plasma and there phosphatase and bilirubin is low in fulminant Wilson
are tumour specific isoenzymes such as Regan, Nagao disease. This might be the result of replacement of
and Kasahara isoenzymes.5 cofactor zinc by copper and subsequent inactivation of
Elevated serum levels of intestinal alkaline phosphatase alkaline phosphtase.23 regardless of the cause of acute
have been found in patients with cirrhosis, particularly hepatic failure a low ratio of alkaline phosphatase to
those with blood group type O, and may be bilirubin is associated with a poor prognosis.24

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Liver Function Tests and their Interpretation

Drugs like cimetidine, frusemide, phenobarbitone and 1. SERUM PROTEINS

phenytoin may increase levels of alkaline phosphtase.5
The liver is the major source of most the serum proteins.
The parenchymal cells are responsible for synthesis of
2. ÿ GLUTAMYL TRANSPEPTIDASE
albumin, fibrinogen and other coagulation factors and
ÿ Glutamyl transpeptidase(GGT) is a membrane bound most of the a and b globulins. 26
glycoprotein which catalyses the transfer of ÿ glutamyl Albumin : Albumin is quantitatively the most important
group to other peptides, amino acids and water. protein in plasma synthesized by the liver and is a useful
indicator of hepatic function. Because the half life of
Large amounts are found in the kidneys, pancreas,
liver, intestine and prostate. The gene for ÿ glutamyl albumin in serum is as long as 20 days, the serum albumin
transpeptidase is on chromosome 22. The levels of ã level is not a reliable indicator of hepatic protein synthesis
glutamyl transpeptidase are high in neonates and infants in acute liver disease. Albumin synthesis is affected not
up to 1 yr and also increase after 60 yr of life. Men have only in liver disease but also by nutritional status, hormonal
balance and osmotic pressure. Liver is the only site of
higher values. Children more than 4 yr old have serum
values of normal adults. The normal range is 0-30IU/L 1,5 synthesis of albumin. 5

In acute viral hepatitis the levels of ÿ glutamyl The serum levels are typically depressed in patients
with cirrhosis and ascites. In patients with or without
transpeptidase may reach its peak in the second or third
ascites, the serum albumin level correlates with
wk of illness and in some patients they remain elevated
for 6 weeks. In EHBA GGT is markedly elevated.5 prognosis.27 In addition the rate of albumin synthesis has
been shown to correlate with the Child- Turcotte or Child-
Often clinicians are faced with a dilemma when they Pugh score.28
see elevated alkaline phosphatase levels and are unable
to differentiate between liver diseases and bony disorders Normal serum values range from 3.5g/dl to 4.5 g/dl.
and in such situations measurement of ÿ glutamyl The average adult has approximately 300 to 500 g of
transferase helps as it is raised only in cholestatic albumin. The serum levels at any time reflect its rate of
disorders and not in bone diseases. 5 synthesis, degradation and volume of distribution.

In liver disease ÿ glutamyl transpeptidase activity Corticosteroids and thyroid hormone stimulate albumin
synthesis by increasing the concentration of albumin
correlates well with alkaline phosphatase levels but rarely
the ÿ glutamyl transpeptidase levels may be normal in mRNA and tRNA in hepatocytes. 29
intra hepatic cholestasis like in some familial intrahepatic The serum albumin levels tend to be normal in diseases
cholestasis. 25 like acute viral hepatitis, drug related hepatotoxicity and
obstructive jaundice. Albumin levels below 3g/dl in
Other conditions causing elevated levels of ÿ glutamyl
transpeptidase include uncomplicated diabetes mellitus, hepatitis should raise the suspicion of chronic liver disease
like cirrhosis which usually reflects decreased albumin
acute pancreatitis and myocardial infarction. Drugs like
phenobarbitone, phenytoin, paracetamol, tricyclic synthesis. In ascites there may be normal synthesis but
the levels may appear reduced because of increased
antidepressants may increase the levels of ÿ glutamyl volume of distribution. 30,31
transpeptidase.
Hypoalbuminemia is not specific for liver disease and
Non-hepatic causes of increased levels of the enzyme
include anorexia nervosa, Gullian barre syndrome, may occur in protein malnutrition, nephrotic syndrome and
5 chronic protein losing enteropathies. 1
hyperthyroidism, obesity and dystrophica myotonica.
As a diagnostic test the primary usefulness of ÿ glutamyl 2. PREALBUM
transpeptidase is limited to the exclusion of bone disease,
as ÿ glutamyl transpeptidase is not found in bone. 1
The serum prealbumin level is 0.2- 0.3 g/L. these levels
fall in liver disease presumably due to reduced synthesis.
OTHER ENZYMES THAT DETECT CHOLESTASIS Because of its short half life, changes may precede
alteration in serum albumin. Determination of prealbumin
has been considered particularly useful in drug-induced
These are the other enzymes that are not routinely
estimated to detect cholestasis. hepatotoxicity.

5 Nucleotidase 3. CERULOPLASMIN SERUM

Leucine aminopeptidase
Normal plasma levels are 0.2-0.4g/L. It is synthesized in
C. Tests of the Liver’s biosynthetic capacity. the liver and is an acute phase protein. The plasma

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B.R.Thapa and A. Walia

concentration rise in infections, rheumatoid arthiritis, major site of synthesis of 11 blood coagulation proteins:
pregnancy, non Wilson liver disease and obstructive fibrinogen, prothrombin, labile factor, stable factor,
jaundice. christmas factor, stuart prowe factor, prekallikrein and high
molecular wt kininogen.1
This is an important diagnostic marker in Wilson
disease, in which the plasma level is usually low. Low Most of these are present in excess and abnormalities
levels may also be seen in neonates, Menke’s disease, of coagulation only result when there is substantial
kwashiorkor, marasmus, protein losing enteropathy, impairment in the ability of the liver to synthesize these
copper deficiency and aceruloplasminemia. factors.

The standard method to assess is the one stage

4. PROCOLLAGE III PEPTIDE
prothrombin time of quick, which evaluate the extrinsic
coagulation pathway. 4
The serum concentration of this peptide appears to
The results of this test may be expressed in sec or as a
increase not only with hepatic fibrosis but also with
inflammation and necrosis. Serial measurement of ratio of the plasma prothrombin time to control plasma
time. Normal control usually is in the range of 9-11
procollagen III may be helpful in the follow up of chronic
liver disease. seconds. A prolongation of more than 2 seconds is
considered abnormal.1

The prolonged PT is not specific for liver diseases and

5. ÿ 1 ANTITRYPSIN
is seen in various deficiencies of coagulation factors, DIC,
and ingestion of certain drugs.
ÿ 1 antitrypsin is a glycoprotein synthesized by the liver In acute and chronic hepatocellular disease the PT may
and is an inhibitor of serine proteinases, especially serve as a prognostic indicator. In acute hepatocellular
elastase. Its normal concentration is 1- 1.6g/L. it is an disease worsening of PT suggests an increased likelihood
acute phase protein, serum levels increase with of acute hepatic failure. The PT is a predictor of outcome
inflammatory disorders, pregnancy and after oral in cases of acetoaminophen over dosage and acute
contraceptive pills (OCP). alcoholic hepatitis. Prolongation of PT is also suggestive
The various alleles coded are M,F,S,Z and null forms. of poor long-term outcome in chronic liver disease.4
PiZZ homozygotes are associated with neonatal hepatitis.
Cirrhosis in adults has been found with ZZ, MZ, SZ and
If the PT returns to normal or improves by at least 30%
FZ phenotypes.
within 24 hr of a single parenteral injection of vitamin K1
Liver disease is usually seen with deficiency of ÿ 1 (5-10 mg), it may be surmised that parenchymal function
antitrypsin, an inherited disorder. Deficiency should be is good and that hypovitaminosis K was responsible for
confirmed by quantitative measurement. the original prolongation of PT. Patients with parenchymal
disease by contrast will show only minimal improvement.
6. a FETO PROTEIN Most patients with extra hepatic obstruction like EHBA
would respond promptly to a single injection of vitamin
K1.1
This protein, the principal one in fetal plasma in early
gestation is subsequently present at very low levels.( <25µg/ The PT is particularly important in the management of
L) It is increased in hepatocellular carcinoma (HCC)and patients with liver disease. It is important to perform before
more than 90% of such patients have raised levels. Raised procedures like liver biopsy and kidney biopsy and it
values are also found in other liver diseases like chronic permits an assessment of the tendency to bleed. In many
hepatitis, in regeneration phase of acute hepatitis and in centers the International normalized ratio (INR) is done in
hepatic metastasis. This is also raised in adenomas place of PT.1
associated with tyrosinemia.
To assess the severity of liver disease the Child Pugh
ÿ feto protein elevation is less frequent when HCC scoring was in use and proved very good to predict the
arises in non cirrhotic liver. Serial determination is of value outcome of the disease. Now with the upsurge of liver
in cirrhotic patients and rise in the values should raise the transplantation the model for end stage liver disease
suspicion of HCC.5 (MELD) and pediatric end stage liver disease (PELD)
scoring system is being followed to prioritize the transplant
7. PROTHROMBIN TIME (PT) surgery.
Because of the shortcomings of the biochemical liver
Clotting is the end result of a complex series of enzymatic function tests, the quantitative function tests are used and
reactions that involve at least 13 factors. The liver is the are shown to be very sensitive but their utility in pediatric

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Liver Function Tests and their Interpretation

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11. Dunn M et al the disappearance rate of glutamic oxaloacetic transaminase
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12. Frankl HD, Merrit JH. Enzyme activity in the serum and common bile duct.
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sensitive procedure. The number of false negatives must aminotransferases levels in blood donors; the contribution of hepatitis C
be reduced by this technique. The use of battery of liver virus. Ann Intern Med 1991; 115 : 882–8
tests is also associated with high specificity especially
14. Park GJH, Lin BPC, Ngu MC et al. Aspartate amino-transferases: alanine
when more than one test is abnormal. The pattern of aminotransferases ratio in chronic hepatitis C infection : is it a predictor of
enzyme abnormality, interpreted inthe context of the cirrhosis? 2000; 15 :
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determined liver disease in specific populations and of undergoing long term hemodialysis: clinical and biochemical appraisal.
Gastroenterology 1995; 109 : 1295-1299.
possible hepatic involvement during systemic illnesses or
16. Cohen GA, Goffinet JA, Donabedian RK et al. Observations on decreased
drug therapies may help the clinician identify the cause of serum glutamic oxaloacetic transaminase (SGOT) activity in azotemic
alterations efficiently. patients. Ann Intern Med 1976; 84 : 275-281.
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