Evaluation of Liver Function Dr. Baghbanian M. Gastroenterologist Shaheed Sadoughi hospital / 2012

Evaluation of Liver Function Dr. Baghbanian M. Gastroenterologist Shaheed Sadoughi hospital / 2012

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
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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
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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 hemecontaining 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 hepatocellular
AST is found in
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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
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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 alcoholinduced 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
→ liver-function tests rapidly evolve typical of
cholestasis.
Aproach to isolated elevation of bilirubin
Enzymes that Reflect Cholestasis
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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
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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 drug-induced 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: 18–20 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:
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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 Budd-Chiari
syndrome.
Liver Test
Abnormal in...
Albumin
Cirrhosis, severe hepatocellular injury
Alkaline phosphatase
Cholestasis, hepatocellular enzyme induction, canalicular injury, children
during bone growth, bone disease, pregnancy (placenta origin)
Aminotransferases
(AST, ALT)
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
Bilirubin
Any acute or chronic liver disease; congenital disorders of bilirubin
metabolism.
5′ nucleotidase
Cholestasis
GGT
Cholestasis; medications, ethanol; rarely anorexia nervosa, hyperthyroidism,
myotonic dystrophy
INR
Impaired synthesis of vitamin K-dependent coagulation factors
Lactate dehydrogenase Ischemic injury, Epstein-Barr virus infection, hemolysis, solid tumor
Uric acid
Alcohol consumption, gout
Aproach to cholestatic liver enzyme
elevations