Title: Liver function tests and functional tests of liver, ultrasound, biopsy
1Liver function tests and functional tests of
liver, ultrasound, biopsy
2Liver Function Tests (LFTs)
- These tests can be used to
- detect the presence of liver disease
- distinguish among different types of liver
disorders - gauge the extent of known liver damage
- follow the response to treatment.
- Liver tests have shortcomings
- They can be normal in patients with serious liver
disease and abnormal in patients with diseases
that do not affect the liver - Liver tests rarely suggest a specific diagnosis
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic,
and will help to decide whether the disease is
acute or chronic
3The Battery of Blood Tests
- To increase both the sensitivity and the
specificity of laboratory tests in the detection
of liver disease, it is best to use them as a
battery. - Those tests usually employed in clinical practice
include - bilirubin
- Aminotransferases (ALT and AST)
- alkaline phosphatase
- Albumin
- /- prothrombin time
- When more than one of these tests provide
abnormal findings, or the findings are
persistently abnormal on serial determinations,
the probability of liver disease is high. - When all test results are normal, the probability
of missing occult liver disease is low.
4Our Patients Results
- Albumin 36 g/l (Ref range 35-45
g/l)Bilirubin(Total) 38 umol/l (Ref range 0-17
umol/l)AlkP 142 Units/l (Ref range 35-100
Units/l)GGT 240 Units/l (Ref range 0-50
Units/l)ALT 85 Units/l (Ref range 0-35
Units/l)AST 160 Units/l (Ref range 0-42
Units/l) - Coagulation profileProthrombin time 14 sec
(Ref range 8-13s)APTT 40 sec (Ref range
25-38s)Plasma Fibrinogen 3.3 g/l (Ref range
1.5-4.0 g/L)
5Whats What???
- Enzymes that reflect damage to Hepatocytes
- Serum Aspartate aminotransferase (AST)
- Serum alanine aminotransferase (ALT)
- Serum lactate dehydrogenase (LDH)
- All cytosolic heptocellular enzymes. ie increase
in blood indicates damage or death of hepatocytes
- ALT is the more specific to the liver
- The pattern of the aminotransferase elevation can
be helpful diagnostically. In most acute
hepatocellular disorders, the ALT is higher than
or equal to the AST. An ASTALT ratio gt 21 is
suggestive while a ratio gt 31 is highly
suggestive of alcoholic liver disease. The AST in
alcoholic liver disease is rarely gt300 U/L and
the ALT is often normal. A low level of ALT in
the serum is due to an alcohol-induced deficiency
of pyridoxal phosphate.
6- Enzymes that Reflect damage to Bile Canaliculi
- alkaline phosphatase
- 5'-nucleotidase
- -glutamyl transpeptidase (GGT)
- Alkaline phosphatase can be elevated in many
other conditions. - GGT is not specific for cholestasis, also can
reflect hepatocyte damage. - In combination raised GGT can help determine if
raised alkaline phosphatase elevations are due to
liver disease - Alkaline phosphatase and 5'-nucleotidase are
found in or near the bile canalicular membrane of
hepatocytes, while GGT is located in the
endoplasmic reticulum and in bile duct epithelial
cells. Reflecting its more diffuse localization
in the liver, GGT elevation in serum is less
specific for cholestasis than are elevations of
alkaline phosphatase or 5'-nucleotidase.Â
7- Indicators of biliary excretory function
- Serum Bilirubin
- Total (conjugated and unconjugated)
- Direct conjugated
- Urine Bilirubin
8- Indicators of Hepatocyte Function
- Proteins secreted into blood
- Serum albumin
- Clotting factors ( prothrombin time)
- Serum albumin is synthesized exclusively by
hepatocytes. Â Because of this slow turnover, the
serum albumin is not a good indicator of acute or
mild hepatic dysfunction only minimal changes in
the serum albumin are seen in acute liver
conditions such as viral hepatitis, drug-related
hepatoxicity, and obstructive jaundice.
Hypoalbuminemia is more common in chronic liver
disorders such as cirrhosis and usually reflects
severe liver damage and decreased albumin
synthesis. albumin levels lt 3 g/dL should raise
the possibility of chronic liver disease - With the exception of factor VIII, the blood
clotting factors are made exclusively in
hepatocytes. Their serum half-lives are much
shorter than albumin, ranging from 6 h for factor
VII to 5 days for fibrinogen. Because of their
rapid turnover, measurement of the clotting
factors is the single best acute measure of
hepatic synthetic function and helpful in both
the diagnosis and assessing the prognosis of
acute parenchymal liver disease. Useful for this
purpose is the serum prothrombin time, which
collectively measures factors II, V, VII, and X.
Biosynthesis of factors II, VII, IX, and X
depends on vitamin K. The prothrombin time may be
elevated in hepatitis and cirrhosis as well as in
disorders that lead to vitamin K deficiency such
as obstructive jaundice or fat malabsorption of
any kind.Â
9- Indicators of Hepatocyte Metabolism
- Blood Ammonia
- Ammonia is produced in the body during normal
protein metabolism and by intestinal bacteria,
primarily those in the colon. The liver plays a
role in the detoxification of ammonia by
converting it to urea, which is excreted by the
kidneys. Striated muscle also plays a role in
detoxification of ammonia, which is combined with
glutamic acid to form glutamine. Patients with
advanced liver disease typically have significant
muscle wasting, which likely contributes to
hyperammonemia in these patients.
10Other laboratory tests
- hepatitis serology to define the type of viral
hepatitis - Reduced a1 antitrypsin levels, phenotypes PiZZ
or PiSZ - Decreased serum ceruloplasmin and increased
urinary copper increased hepaticcopper level - Elevated iron saturation and serum ferritin
genetic testing for HFE gene mutations - autoimmune markers
- to diagnose primary biliary cirrhosis
(antimitochondrial antibody AMA), sclerosing
cholangitis (peripheral antineutrophil
cytoplasmic antibody P-ANCA), and autoimmune
hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody) - Serum Vitamin levels
- not only in bile responsible for the absortption
of fat-souble vitamins, the liver is respobsible
for storage of all vitamins including
water-soluble
11Type of Disorder Bilirubin Aminotransferases Alkaline Phosphatase Albumin Prothrombin Time
Hemolysis/Gilbert's syndrome Normal to 86Â mol/L (5 mg/dL) 85 due to indirect fractions No bilirubinuria Normal Normal N Normal
Acute hepatocellular necrosis (viral and drug hepatitis, hepatotoxins, acute heart failure) Both fractions may be elevated Peak usually follows aminotransferases Bilirubinuria Elevated, often gt500 IU ALT gtAST Normal to lt3 times normal elevation N Usually normal. If gt5X above control and not corrected by parenteralvitamin K, suggests poor prognosis
Chronic hepatocellular disorders Both fractions may be elevated Bilirubinuria Elevated, but usually lt300 IU Normal to lt3 times normal elevation low Often prolonged Fails to correct with parenteralvitamin K
Alcoholic hepatitis Cirrhosis Both fractions may be elevated Bilirubinuria ASTALT gt 2 suggests alcoholic hepatitis or cirrhosis Normal to lt3 times normal elevation low Often prolonged Fails to correct with parenteralvitamin K
Intra- and extra-hepatic cholestasis (Obstructive jaundice) Both fractions may be elevated Bilirubinuria Normal to moderate elevation Rarely gt500 IU Elevated, often gt4 times normal elevation N Normal If prolonged, will correct with parenteralvitamin K
Infiltrative diseases (tumor, granulomata) partial bile duct obstruction Usually normal Normal to slight elevation Elevated, often gt4 times normal elevation Fractionate, or confirm liver origin with 5' nucleotidase or        glutamyl transpeptidase N Normal
12Imaging
- Ultrasound is the first diagnostic test to use.
It shows - dilation of intrahepatic or extrahepatic biliary
tree - Gallstones
- Steatosis
- space-occupying lesions within the liver (enables
the clinician to distinguish between cystic and
solid masses) - Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins
and determine the direction of blood flow - CT and MRI are indicated for
- identification and evaluation of hepatic masses
- staging of liver tumours
- preoperative assessment.
- With regard to mass lesions, sensitivity and
specificity remains a problem, and often two and
sometimes three studies are needed before a
diagnosis can be reached. - Radiographic studies that strongly suggest
cirrhosis include a small, nodular liver,
ascites, splenomegaly, intra-abdominal varices,
or portal and hepatic vein thrombosis however,
no test is considered a diagnostic gold standard.
The current best test for diagnosing cirrhosis is
liver biopsy.
13- Magnetic resonance cholangiopancreatography
(MRCP) and endoscopic retrograde
cholangiopancreatography (ERCP) are the
procedures of choice for visualization of the
biliary tree. (Through the endoscope, the
physician can see the inside of the stomach and
duodenum, and inject dyes into the ducts in the
biliary tree and pancreas so they can be seen
on xray) - Recently, methods using elastrography have been
developed to measure hepatic stiffness as a means
of assessing hepatic fibrosis. US elastrography
is now undergoing evaluation for its ability to
detect different degrees of hepatic fibrosis and
to obviate the need for liver biopsy in assessing
disease stage. - Nuclear Medicine Scans show gallbladder filling
and emptying. Inject radioactive dye, excreted by
bile ie. accumulated in gallbladder, infusion of
CCK, then can watch empty. - Interventional radiologic techniques allow the
biopsy of solitary lesions, insertion of drains
into hepatic abscesses, measurement of portal
pressure, and creation of vascular shunts in
patients with portal hypertension.
14Percutaneous biopsy
- There have been great advances made in hepatic
imaging, although no method is suitably accurate
in demonstrating underlying cirrhosis. Cirrhosis
is identified by histopathologic examination of
the liver - In selected instances, liver biopsy is necessary
for diagnosis but is more often useful in
assessing the severity (grade) and stage of liver
damage, in predicting prognosis, and in
monitoring response to treatment -
- Biopsy of the liver is a safe procedure that can
be easily performed at the bedside with local
anesthesia. Liver biopsy is of proven value in
the following situations - (1) hepatocellular disease of uncertain cause
- (2) prolonged hepatitis with the possibility of
chronic active hepatitis - (3) unexplained hepatomegaly
- (4) unexplained splenomegaly
- (5) hepatic filling defects by radiologic
imaging - (6) fever of unknown origin
- (7) staging of malignant lymphoma.
- Liver biopsy is most accurate in disorders
causing diffuse changes throughout the liver and
is subject to sampling error in focal
infiltrative disorders such as hepatic
metastases. Liver biopsy should not be the
initial procedure in the diagnosis of
cholestasis.