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Liver function tests and functional tests of liver, ultrasound, biopsy Liver Function Tests (LFT s) These tests can be used to detect the presence of liver disease ... – PowerPoint PPT presentation

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Title: Liver function tests and functional tests of liver, ultrasound, biopsy


1
Liver function tests and functional tests of
liver, ultrasound, biopsy
2
Liver 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

3
The 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.

4
Our 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)

5
Whats 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. 

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.  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. 

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.

10
Other 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

11
Type of Disorder Bilirubin Aminotransferases Alkaline Phosphatase Albumin Prothrombin Time
Hemolysis/Gilbert's syndrome Normal to 86 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

12
Imaging
  • 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.

14
Percutaneous 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.
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