LIVER FUNCTION TESTS

Presented by- Dr. Arshiya Kaura ( JR 1)

 BILIARY CANALICULI
INTRALOBULAR BILE DUCTULES
(CANALS OF HEARING)

BILE DUCTULES IN PORTAL TRACTS

BILE DUCTULES IN PORTAL TRACTS

INTERLOBULAR BILE DUCTS

RIGHT AND LEFT HEPATIC DUCTS

COMMON HEPATIC DUCT CYSTIC DUCT GALLBLADDER

COMMON BILE
DUCT
 NON-HEPATIC CAUSE OF ABNORMAL LIVER FUNCTION TEST

HIGH LEVELS OF BILIRUBIN ARE SEEN IN PATIENTS

WITH:
HEPATITIS
INEFFECTIVE ERYTHROPOIESIS
RESORPTION OF A LARGE HEMATOMA
LIVER CIRRHOSIS
BILE DUCT OBSTRUCTION
GALLBLADDER CANCER
GENETIC DISEASE LIKE GILBERTS SYNDROME
INCREASED SERUM ALKALINE PHOSPHATASE
• PREGNANCY
• BONE DISEASE
LOW SERUM ALBUMIN
• POOR NUTRITION STATUS
• PROTEINURIA
• MALABSORPTION
• SEVERE ILLNESS CAUSING PROTEIN CATABOLISM
INCREASED AMINOTRANSFERASE:
MUSCLE INJURY
ALCOHAL ABUSE
MYOCARDIAL INFACTION
 Bilirubin

• Formed by heme degradation ( 80% from hb ,

20% from other heme containing protiens.)
• Daily 300 mg or 4mg/kg bilirubin is formed.
• Heme oxygenase ( SER ) biliverdin biliverdin
reductase ( cytoplasm).
• Bilirubin is a hydrophobic element which is
combined with albumin.
• Dissosiated from albumin when it is ready to
enter liver.
• As soon as bilirubin enters hepatocytes it binds to glutathione
to prevent reflux.
• Bilirubin is conjugated by UDP glucuronyl transferase to form
bilirubin diglucuronide.
• Bilirubin diglucuronide is excreted via canalicular membrane
into bile.
• MRP 2 present on canalicular memberane which allows
Bilirubin diglucuronide to be converted into bile.( ATP
dependent process )
• MRP3  BILIRUBIN GLUCORONIDE ( water soluble )
• Conjugated bilirubin seen in urine.
 UROBILINOGEN

• Bilirubin diglucuronide reaches colon where it is

deconjugated by bacteria and forms
UNCOJUGATED BILIRUBIN which is converted to
UROBILINOGEN.
• 80 % is excreted in stool.
• 15-20% undergoes Enterohepatic Circulation
• Small amnts 1-2 % are absorbed in systemic
circulation and traces present in urine. ( normal )
• urobilinogen in urine - hemolysis/
cirrhosis ( non working liver)
• Absent urobilinogen  obstruction of biliary
tree ( no conjugated bilirubin coming)
 Bilirubin estimation

• Total bilirubin 1- 1.3 mg/dl

• Indirect bilirubin ( unconjucated) 0.2 – 0.9 mg/dl
• Direct bilirubin ( conjugated ) 0 – 0.3 mg/dl

• >85% of total is indirect then it is INDIRECT

HYPERBILIRUBINEMIA. ( prehepatic)
• >50% of total is direct then it is DIRECT HYPERBILIRUBINEMIA.
( post hepatic)
• 15- 50% of total is direct then it is HEPATIC
HYPERBILIRUBINEMIA. ( hepatic)
 INDIRECT HYPERBILIRUBINEMIA with no
hemolysis
• Drugs rifapincin , probencin
• herediatary unconjucated hyperbilirubineania
• (GILBERTS SYND.)
• (CRIGGLER NAJAR TYPE 2)
 Van den berg reaction / DIAZO reaction

• Blood + van den berg reagent  purple pink colour ( conjugated bilirubin or
direct)
• Alcohol + van den berg reagent 
( total bilirubin )
TOTAL – DIRECT = INDIRECT BILIRUBIN
• Serum Protiens released by liver are
• POSITIVE ACUTE REACTANT ( levels are raised in
inflammation)
• 4 protiens which are NEGATIVE ACUTE PHASE
REACTANT
 ALUBUMIN
 TRANSFERRIN
 AFP
 TRANSTHERATIN
 Serum proteins
• Routinely done estimations are:
• Total serum proteins (normal 6.7–8.6 g/dL)
• Serum albumin (normal 3.5–5.5 g/dL) is
produced solely by the liver.
• Serum globulin (normal 2–3.5 g/dL)
• Albumin/globulin (A/G) ratio (normal 1.5–
3:1).
Serum Albumin
• Normal levels – 15g/day
• MAKER OF CHRONICITY in hepatic diseases.
• IT IS A NEGATIVE ACUTE PHASE REACTANT

Serum globulin
• Polyclonal hyper gammaglobinemia suggests of
AUTOIMMUNE HEPATITIS.
• Monoclonal hyper gammaglobinemia suggests
of PLASMA CELL DYSKRASIS
Serum albumin:
• Albumin is synthesized exclusivelyin liver and constitutes
about 60% of total proteins in serum in liver disease.
• Half-life is about 20 days and therefore fall in its level in
response to decreased synthesis is not immediately apparent.
• Therefore, in acute liver disease (e.g. viral hepatitis), there is
little change in albumin level.
• Serum albumin level is low in chronic liver disease (cirrhosis)
and correlates with synthetic capacity of hepatocytes;
therefore, it is helpful in following progression of cirrhosis. Also,
fall in serum albumin level correlates with severity of ascites.
• In cirrhosis and in chronic active hepatitis, serum gamma
globulins are increased due to inflammation. Low albumin and
raised gamma globulins in serum cause reversal of
albumin/globulin ratio.
Causes of decreased serum albumin:
• Decreased intake: malnutrition.
• Decreased absorption: malabsorption syndromes.
• Decreased synthesis: liver disease, chronic infections.
• Increased catabolism: thyrotoxicosis, fever, malignancy,
infections.
• Increased loss: nephrotic syndrome, severe burns,
protein-losing enteropathies, ascites
• Increased blood volume: pregnancy, congestive cardiac
failure.
As low serum albumin occurs in diseases other than
those of liver, serum albumin is a sensitive but nonspecific
test for liver disease.
 Serum protein electrophoresis
In liver disease, following changes may be seen on protein
electrophoresis
1. In cirrhosis, albumin may be reduced and there may
be polyclonal increase of IgG and IgA, with β-γ
bridging. (IgA migrates between β and γ regions
which obscures the demarcation between β and γ
peaks).
2. In primary biliary cirrhosis, there is polyclonal
increase of IgM.
3. In α1-antitrypsin deficiency (associated with
cirrhosis) α1- globulin band is reduced.
4. In chronic active hepatitis, IgG is elevated.
Serum protein electrophoresis patterns and densitometer scans in normal
individuals and in cirrhosis of liver
 LIVER ENZYMES
• ALT (SGPT) ALANINE AMINO TRANSFERASE
• Comes from cytoplasm of liver
• LIVER SPECIFIC( only site from which ALT Is Produced Is
Liver)

• AST (SGOT) ASPARTATE AMINO TRANSFERASE

• Comes from both cytoplasm and mitochondria of liver.
• NOT LIVER SPECIFIC ( Can be produced in various organs
like skeletal muscle, cardiac muscle and also liver seen in
RHABDOMYOLYSIS AND MI respectively.)
Alanine aminotransferase(ALT): cytosol;
Aspartate aminotransferase (AST): mitochondria and cytosol;
Alkaline phosphatase (ALP): canalicular surface;
Gamma glutamyl transferase (GGT): canalicular surface and
microsomes;
5’ NT: canalicular surface.
• The pattern of hepatocyte injury determines
the enzymes elevated:
• cytoplasmic damage: elevated AST,ALT, and
LDH;
• Mitochondrial damage: elevated AST;
• Cholestatic damage: elevated ALP and GGT
• ALT and AST have got normal value <30 units /litre.
• In any normal person ALT> AST( AST is more rapidly
cleared by the reticuloendothelial system)
• “MARKER of ACUTE HEPATOCELLULAR INJURY”
always indicates enzymes are increased. As
whenever there is injury due to any cause( drug,
toxin, ischemia ,alcohol) essentially the viable
hepatocytes are going to release AST and ALT into
blood as most sensitive marker for hepatocellular
injury.
• A person with liver disease can present with
• ACUTE HEPATITIS (Acute Hepatocellular Injury)
• CHRONIC HEPATITIS
• CIRRHOSIS ( which can go into decomposition with
portal hypertension and HCC)
• Classical example of portal hypertension is ascitis
and splenomegaly.
• Hepatitis A is always present as acute hepatitis.
Whereas in hepatitis B we can see acute, chronic
hepatitis and also maybe cirrhosis.
 ACUTE HEPATOCELLULAR INJURY
• In acute hepatitis ALT and AST are always raised which is
more than 1000 international units / litre
• Can be due to
• Acute Viral hepatitis
• Drug induced hepatitis
• Toxin induced hepatitis(e.g. carbon tetrachloride),
• Ischemic hepatitis (centrilobular necrosis due to
ischemia (congestive cardiac failure).)
• But any acute bile duct obstruction can produce ALT and
AST more than 1000u/l.
• In acute hepatitis with underlying chronic liver
disease AST>ALT, and ALT and AST>1000 u/l.
• Generally Acute Hepatitis has good prognosis
but acute hepatitis where ALT and AST are
not raised more than 200-400 u/l and has bad
prognosis is ALCOHOLIC HEPATITIS.
• Also in alcoholic hepatitis AST> ALT.
 ALCOHOLIC LIVER DISEASE
• AST levels < 200-400 units/l
• AST/ALT 2:1 – Acute hepatitis mostly
suggestive of alcoholic hepatitis.
• AST/ALT 3:1– diagnostic of alcoholic hepatitis.
• Pyridoxal phosphate deficiency .
• ALT requires more of PLP than AST , so ALT def
is more in alcoholics.
 CHRONIC HEPATITIS
• Can Lead To Cirrhosis which leads to
decomposition and HCC.
• Chronic heptitic can be from HEPATITIS B
(ACUTE HEPATITIS).
• Certain diseases De-NOVO starts as chronic eg
HEMACHROMATOSIS.
• Certain disease straight land up as chronic as
HEPATITIS B from mother.
• Chronic hepatitis diagnosis is difficult as it is
asymptomatic, only fatigue and other
symptoms are seen.
• So, routine monitoring of enzymes is
important.
• ALT and AST < 150 units/l ( 5 times the
normal value). And always ALT> AST
• ALT and AST < 150 units /l but AST>ALT –
definitive Indicative for cirrhosis.
 Major causes
• NASH ( NON- ALCOHOLIC STEATOHEPATITIS)
• CHRONIC VIRAL HEPATITIS
• WILSONS DISEASE
• AUTOIMMUNE HEPATITIS
• HEMACHROMATITIS
• AST/ALT> 1 is an indicator of cirrhosis in all these
conditions/ impaired function hepatic blood flow
and decreased sinusoidal uptake of AST
 ALKALINE PHOSPHATASE ( ALP)
• Normal value 40-140 unit/l
• Elevation is significant only if it is 4 times the
upper limit of normal.
• It is produced by many tissues (bone, liver,
intestine and placenta) and is excreted in the
bile.
• Conditions other than liver disease in which
ALP is elevated.
 Pregnancy
 Elderly (>70 yrs)
 After Heavy meal
 Blood group O +ve
 Adolescent age group
• If the elevation is more than 4 times of normal
then there is possibility of cholestasis.
• ALP> 4times ( 800 units/l)
• But ALP is not specific marker of cholestasis.
• Is present in canalicular membrane of liver.( b/w
2 hepatocytes.
• In cholestasis, accumulated bile acids dissolve
canalicular side of hepatocyte membrane and
enzymes are released in blood. Therefore,
diseases that affect mainly hepatocyte secretion
have elevated levels of ALP.
Sites of cholestasis
 Conjugated hyperbilirubinemia
• >50% of total is direct.
• ALP> 4times and confirm with GGT ( raised)
• USG abdomen
• If ducts are not dilated INTRAHEPATIC CHOLESTASIS.
• Causes of INTRAHEPATIC CHOLESTASIS.
• Drugs {Estrogen,
azathioprine,allopurinol,sulphonamides( granulomatous hep.),
erythromycin , amoxyclav (vanishing bile duct)}
• Sarcoidosis
• Primary biliary cholangitis ( autoimmune destruction of bile duct)
• CMV
• INHERITED CONJUGATED HYPERBILIRUBINEMIA( DUBBIN JOHNSON,
ROTORS)
 Gamma Glutamyl Transferase
• Specific marker for cholestasis.
• This enzyme confirms hepatic origin.
• Its serum level parallels serum alkaline
phosphatase.
• It is used to confirm that raised serum alkaline
phosphatase is due to hepatobiliary disease.
Estimation of this enzyme is particularly useful in
following liver diseases:
1. Alcoholism:
• Increased enzyme activity is present in alcoholism,
and is a helpful clue in suspected cases of occult
alcoholism (even in the absence of alcoholic liver
disease).
• It is also helpful in follow up of patients with
chronic alcoholism.
• Marked elevation of GGT occurs in acute alcoholic
hepatitis.
2. Cholestasis:
• Elevation of GGT generally parallels that of ALP and 5’-
NT in liver disease.
• Elevation of ALP is not specific for liver disease.
• Elevation of both ALP and GGT points towards liver
disease.
3. Recovery in acute hepatitis:
Serum GGT is the last enzyme to return to normal
following acute hepatitis and its normalization is
indicative of a favourable outcome.
 5’ nucleotidase
• It is also marker of cholestasis
• But is produced both by liver and bone, so not
a specific marker for liver.
• It is also a phosphatase derived from the liver.
• Estimation of 5’-NT is helpful in deciding
whether increased ALP is due to liver disease
or due to increased osteoblastic activity in
growing children.
 Quantitative LFT’S
• Prothrombin time
• Activated Prolonged Prothrombin time
• INR
• PLATELET COUNT – thrombocytopenia – 1st
marker to be raised in portal hypertension.
 Prothrombin Time (PT)
 Most of the coagulation proteins are synthesized in
the liver.
 Vitamin K is required for the synthesis of factors II,
VII, IX, and X by the hepatocytes; therefore these
factors are called as vitamin K-dependent factors.
 Synthesis of these factors is deficient in
hepatocellular disease.
 In obstructive jaundice, vitamin K (a fat-soluble
vitamin) cannot be absorbed due to the absence of
bile in the intestine.
PT measures three out of four vitamin K-dependent
factors (II, VII, and X) and is prolonged in hepatocellular
disease and in obstructive jaundice. Intramuscular
injection of vitamin K corrects prolonged PT in
obstructive jaundice but not in hepatocellular jaundice.
In acute fulminant liver failure, marked prolongation of
PT is an unfavourable prognostic sign.
To distinguish between a prolonged PT due to
hepatocellular disease from that due to cholestasis
with fat malabsorption, PT is repeated after
administration of vitamin K.
Reduction of prolonged PT occurs in cholestatic liver
disease, but not in hepatocellular disease.
 ACUTE HEPATITIS E v/s DIC
PT/aPTT/ INR RAISED PT/aPTT/ INR
RAISED
SERUM FIBRINOGEN NORMAL DECREASED

SERUM FIBRIN DEGENERATION PRODUCTS

NORMAL INCREASED

D – DIMER LEVELS NORMAL INCREASED

FACTOR VIII NORMAL DECREASED

(As factor VIII is only factor is not ( rest all factors
PRODUCED by liver REST ALL ARE are also
PRODUCED) it is produced solely by decreased )
vascular endothelium
 HEPATITIS v/s VIT. K def.
PT/aPTT/ PT RAISED BUT aPTT normal ( as
INR factor VII is affected and has
RAISED shortest t ½)
Later stages both are raised

MELD score for Acute Hepatitis

INR , Serum bilirubin, creatinine