Evaluation of Liver Function
Dr. Baghbanian M.
Gastroenterologist
Shaheed Sadoughi hospital / 2012
liver tests
(1) detect the presence of liver
disease
(2) distinguish different types of liver
disorders
(3) extent of liver damage
(4) follow the response to treatment
Liver tests
Can be normal in serious liver disease
Can be abnormal in non hepatic diseases
Rarely suggest a specific diagnosis
They suggest a general category of liver
disease, such as hepatocellular or
cholestatic
liver carries out thousands
of biochemical functions
most cannot be easily measured by blood
tests.
Laboratory tests measure only a limited
number of these functions.
Aminotransferases /Alkaline
phosphatase
do not measure liver function at all.
Rather, they detect:
liver cell damage
interference with bile flow.
Thus, no one test FOR assess the liver's
total functional capacity.
Liver test
Bilirubin
aminotransferases
alkaline phosphatase
albumin
prothrombin time tests.
USE MULTIPLE TEST for
detection of liver disease
probability of liver disease is high
When :
more than one of these tests are abnormal
tests persistently abnormal on serial
determinations
probability of liver disease is
lowWhen:
all test results are normal
Tests Based on Detoxification and
Excretory Functions
Serum Bilirubin
Blood Ammonia
Serum Enzymes
Serum Bilirubin
breakdown product of the porphyrin of
heme-containing proteins
two fractions:
Conjugated = direct
water soluble
excreted by the kidney.
Unconjugated = indirect
insoluble in water
bound to albumin in the blood.
Normal Serum Bilirubin
Total = 1 - 1.5 mg/dL.
Direct <15% of the total considered
indirect
upper limit of normal for conjugated =
0.3 mg/dL.
Isolated unconjugated
hyperbilirubinemia
is rarely due to liver disease
Causes:
hemolytic disorders
genetic conditions such as :
Crigler-Najjar
Gilbert's syndromes
bilirubin elevated but
<15% direct
should prompt a workup for hemolysis
In the absence of hemolysis, an
isolated, unconjugated hyperbilirubinemia
in an otherwise healthy patient can be
attributed to Gilbert's syndrome, and no
further evaluation is required.
conjugated
hyperbilirubinemia
always implies liver or biliary tract
disease.
In most liver diseases, both conjugated
and unconjugated fractions of the
bilirubin tend to be elevated
rate-limiting step in
bilirubin metabolism
transport of conjugated bilirubin into the
bile canaliculi
not conjugation
Fractionation of the
bilirubin
rarely helpful in determining the cause of
jaundice
Except : purely unconjugated
hyperbilirubinemia,.
Degree of elevation of
bilirubin
not as a prognostic marker
But is important in :
viral hepatitis: higher bilirubin greater
hepatocellular damage.
alcoholic hepatitis: Total serum bilirubin
correlates with poor outcomes
component of the Model for End stage Liver
Disease (MELD)
drug-induced liver disease: elevated
total serum bilirubin indicates more severe
injury.
Urine Bilirubin
Unconjugated bilirubin binds to albumin
in the serum and is not filtered by the
kidney.
any bilirubin in urine is conjugated
bilirubin;
the presence of bilirubinuria implies
the presence of liver disease.
In patients recovering from jaundice, the
urine bilirubin clears prior to the serum
bilirubin.
Blood Ammonia
is produced
during normal protein metabolism
intestinal bacteriain the colon.
liver plays : detoxification of ammonia
by converting it to urea excreted by the
kidneys
Striated muscle detoxification of
ammonia(combination with glutamic
acid )
Elevated ammonia levels
Has very poor correlation with:
presence or severity of acute
encephalopathy
hepatic function.
Elevated ammonia levels
occasionally useful for occult liver
disease in mental changes.
correlate with outcome in fulminant
hepatic failure.
in severe portal hypertension and
shunting around the liver even in
normal or near-normal hepatic
function.
Serum Enzymes
The liver contains thousands of enzymes
These enzymes have no known
function
probably cleared by reticuloendothelial
cells
liver cells damage entrance of Enzymes
into serum
3 type of LIVER enzyme
tests
1) enzymes whose elevation reflects
damage to hepatocytes
2) enzymes whose elevation reflects
cholestasis
3) enzyme tests that do not fit either
pattern.
Enzymes that Reflect
Damage to Hepatocytes
include:
aspartate aminotransferase (AST) =
serum glutamic oxaloacetic transaminase
(SGPT)
alanine aminotransferase (ALT) =
serum glutamic pyruvic transaminase(SGPT)
sensitive indicators of liver cell injury
most helpful in recognizing acute
AST is found in
Liver
cardiac muscle
skeletal muscle
kidneys
brain
pancreas
lungs
leukocytes, and erythrocytes
ALT is found primarily in the liver
and is more specific for liver injury.
The aminotransferases are normally
present in the serum in low
concentrations.
Aminotransferases
damage to the liver cell enzymes
release into blood
Liver cell necrosis is not required
poor correlation with degree of liver cell
damage
not prognostic in acute hepatocellular
disorders.
Levels of aminotransferases
normal : 10-40 U/L.
<300 U/L are nonspecific and may be
found in any type of liver disorder.
Minimal ALT elevations in
asymptomatic blood donors rarely
indicate severe liver disease; fatty liver
is the most cause.
Aminotransferases >1000
U/L
Extensive hepatocellular injury
such:
1) viral hepatitis
2) ischemic liver injury (prolonged
hypotension or acute heart failure)
3) toxin- or drug-induced liver injury.
The pattern of the
aminotransferase
acute hepatocellular disorders: ALT
AST.
chronic viral hepatitis : ALT AST
cirrhosis : AST ALT
Alcoholic liver disease
AST/ALT >2:1 is suggestive
AST/ALT >3:1 is highly suggestive
The AST is rarely >300 U/L
ALT is often normal.
A low level of ALT in the serum is due to
an alcohol-induced deficiency of
pyridoxal phosphate.
Aproach to asymptomatic elevation
of serum aminotransferase
Obstructive jaundice
Aminotransferases not greatly elevated
Exception: passage of a gallstone into
the common bile duct acute biliary
obstruction aminotransferases 1000
2000 decrease quickly liverfunction tests rapidly evolve typical of
cholestasis.
Aproach to isolated elevation of bilirubin
Enzymes that Reflect Cholestasis
Are usually elevated in cholestasis
Alkaline phosphatase
5'-nucleotidase
Gama glutamyl transpeptidase (GGT)
Gama glutamyl transpeptidase
(GGT)
GGT is more diffuse in liver is less
specific for cholestasis than alkaline
phosphatase or 5'-nucleotidase.
GGT in occult alcohol use?
lack of specificity / questionable.
Serum alkaline phosphatase
found in :
Liver
Bone
Placenta
Small intestine
ALKP non pathologically
elevated
Age > 60
Blood types O and B after fatty meal
(influx of intestinal ALKP into the blood.)
Children and adolescents undergoing
rapid bone growth, (bone)
Late in normal pregnancies (influx of
placental )
Elevation of liver-derived
alkaline phosphatase
Not specific for cholestasis
< 3 fold occur in :
any type of liver disease.
>4 fold occur in:
cholestatic liver disorders
infiltrative liver diseases such as cancer
and amyloidosis
If an elevated ALKP is only
finding
First aproach : ALKP electrophoresis.
Second approach : inactivation by heat
heat-stable : placenta or a tumor is the
source.
heat unstable: intestinal, liver, and bone
measurement of serum 5'nucleotidase or GGT
In the absence of jaundice or
elevated aminotransferases, an
elevated ALKP of liver origin
Often: early cholestasis
less often: hepatic infiltration by tumor
or granulomata.
isolated elevations of the
alkaline phosphatase
Hodgkin's disease
diabetes
hyperthyroidism
congestive heart failure
amyloidosis
inflammatory bowel disease.
Level of ALKP
IS NOT helpful in distinguishing
between intrahepatic and extrahepatic
cholestasis
obstructive jaundice due to cancer, common
duct stone, sclerosing cholangitis, or bile duct
stricture.
Alkaline phosphatase
increased in :
intrahepatic cholestasis due to druginduced hepatitis
primary biliary cirrhosis
rejection of transplanted livers
rarely, alcohol-induced steatohepatitis.
Serum alkaline phosphatase
Greatly elevated in hepatobiliary
disorders in AIDS
AIDS cholangiopathy due to cytomegalovirus
or cryptosporidial infection
tuberculosis with hepatic involvement
Aproach to isolated
elevation of ALKP
Serum Albumin
Synthesized exclusively by hepatocytes.
Long half-life: 1820 days
Not a good indicator of acute or mild
hepatic dysfunction (slow turnover)
Hypoalbuminemia
Common in chronic liver disorders such as
cirrhosis than in acute liver disease
Reflects severe liver damage and decreased
albumin synthesis.
is not specific for liver disease and occur in:
protein malnutrition
protein-losing enteropathies
nephrotic syndrome
chronic infections that inhibit albumin synthesis.
Serum Globulins
Immunoglobulins produced by B
lymphocytes
Globulins are increased in chronic
hepatitis and cirrhosis.
increased Serum Globulins
In cirrhosis: due to the increased
synthesis of antibodies against
intestinal bacteria.
Cause : cirrhotic liver fails to clear bacterial
antigens that normally reach through the
hepatic circulation.
Specific globulins are helpful in
recognition of certain liver
diseases
Diffuse polyclonal IgG in
autoimmune hepatitis
IgM in primary biliary cirrhosis
IgA in alcoholic liver disease.
Coagulation Factors
Are made exclusively in hepatocytes.
Exception: factor VIII,
(which is produced by vascular endothelial
cells)
Coagulation Factors
Half-lives are shorter than albumin
6 h for factor VII to 5 days for fibrinogen.
Single best acute measure of hepatic
synthetic function FOR diagnosis and
assessing the prognosis of acute
parenchymal liver disease.
Coagulation Factors
Prothrombin time : measures factors II,
V, VII, and X.
(25710)
Depends on vitamin K: synthesis of
factors II, VII, IX, and X
(29710)
Prothrombin time
May be elevated in :
hepatitis
cirrhosis
vitamin K deficiency
obstructive jaundice
fat malabsorption
prothrombin time >5 s
above control
If not corrected by parenteral
vitamin K
is a poor prognostic sign in acute viral
hepatitis and other acute and chronic
liver diseases.
MELD (model of end stage liver
disease)
Allocate for liver transplantation.
Has 3 component:
INR,
Total serum bilirubin
Creatinine
Percutaneous Liver Biopsy
Is a safe procedure
Easily performed at the bedside
With local anesthesia and ultrasound
guidance.
Percutaneous Liver Biopsy
Indication
(1)Hepatocellular disease of uncertain
cause
(2) Prolonged hepatitis (chronic active
hepatitis)
(3) Unexplained hepatomegaly
(4) Unexplained splenomegaly
(5) Hepatic filling defects IN imaging
(6) Fever of unknown origin
(7) Staging of malignant lymphoma
Liver biopsy
is most accurate in disorders causing
diffuse changes IN liver
Sampling error in focal infiltrative
disorders such as hepatic metastases.
Should not be the initial procedure in
cholestasis.
Liver biopsy
Contraindications
Significant ascites
Prolonged INR
Under these circumstances, the biopsy
can be performed via the transjugular
approach
Ultrasonography
First diagnostic test in cholestasis:
dilated intrahepatic
extrahepatic biliary tree
gallstones.
space-occupying lesions IN liver,
distinguish between cystic and solid
masses, and helps direct percutaneous
biopsies.
Ultrasound with Doppler
Detect the patency of the :
portal vein
hepatic artery
hepatic veins
First test in patients suspected BuddChiari syndrome.
Abnormal in...
Liver Test
Cirrhosis, severe hepatocellular injury
Albumin
Cholestasis, hepatocellular enzyme induction, canalicular injury, children
during bone growth, bone disease, pregnancy (placenta origin)
Alkaline phosphatase
Hepatocellular injury (ethanol, drug-induced hepatitis, hepatitis B and C,
ischemic injury, chronic liver disease, NAFLD, chronic viral hepatitis,
alcoholism, nonspecific viral injury, and cholestatic or replacement disease);
acute biliary obstruction; rarely in hyperthyroidism, celiac disease, skeletal
muscle disease
Aminotransferases
(AST, ALT)
Any acute or chronic liver disease; congenital disorders of bilirubin
metabolism.
Bilirubin
Cholestasis
5 nucleotidase
Cholestasis; medications, ethanol; rarely anorexia nervosa, hyperthyroidism,
myotonic dystrophy
GGT
Impaired synthesis of vitamin K-dependent coagulation factors
INR
Ischemic injury, Epstein-Barr virus infection, hemolysis, solid tumor
Lactate dehydrogenase
Alcohol consumption, gout
Uric acid
Aproach to cholestatic liver
enzyme elevations
