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Liver

There are number of diagnostic parameters for investigating liver health and function, including bile acids, bilirubin, Hyaluronic Acid (HA), aminotransferases, GLDH and other enzymes.

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Bile Acids for Obstetric Choleostasis

Bile acids are synthesised in the liver and stored in the gallbladder.  When food is consumed bile acids are secreted into the intestine where they facilitate the formation of micelles and promote processing of dietary fat.

Bile Acids Testing can aid diagnosis of cholestasis, portosystemic shunt and bile acids malabsorption.

Raised Bile Acids in pregnancy are indicative of Obstetric Cholestasis, a condition that is associated with foetal distress, premature labour and still birth.  Determination of bile acids can also assist with the diagnosis of other liver diseases and bile acid malabsorption. Increased bile acids in fasting or postprandial state are considered a specific indicator of liver disease and decreased levels are associated with bile acid malabsorption.

Bilirubin for Neonatal Jaundice

Bilirubin is a product of haem catabolism.  Small amounts of bilirubin are present in the blood as a result of damaged and dead red blood cells which are disposed of via the spleen. When too many cells are being destroyed or the liver is unable to remove all of the bilirubin from the blood the levels of bilirubin increase and can result in jaundice.

New born babies lack the intestinal bacteria that help process bilirubin and neonatal bilirubineamia is not uncommon.  Typically this resolves itself in a couple of days, but in some instances the newborn's blood may have been destroyed because of blood typing incompatibilities or other genetic factors. It is important that the levels of bilirubin do not get too high in young babies as excessive bilirubin damages developing brain cells and can cause mental retardation, physical abnormalities or blindness.

Hyaluronic Acid for Liver Fibrosis

There are a number of diseases that can result in liver fibrosis such as viral hepatitis, alcoholism, fatty liver disease or genetic disorders. Fibrotic injury distorts the normal liver architecture and can result in organ dysfunction and hypertension. Fibrosis can progress to cirrhosis and also lead to hepatocellular carcinoma (HCC). Serum Hyaluronic Acid measurement can assist in diagnosis and monitoring of liver fibrosis and cirrhosis.

Hyaluronic Acid is a polysaccharide produced by fibroblasts throughout the body and plays a structural role in the connective tissue matrix. Whilst high concentrations of HA may be found in connective tissues and joints, serum levels of HA are typically low in healthy individuals as circulating HA is rapidly removed from the blood by sinusoidal endothelial cells (SECs) in the liver. The HA binds to cell surface receptors and is then endocytosed (internalized) by the cell and degraded. A strong correlation is seen between serum HA and liver pathology, particularly in cirrhosis, where a reduction in HA receptors on the SECs reduces the rate at which HA can be removed resulting in an increase in circulating HA.

Liver Function – Aminotransferase Enzymes

Alanine aminotransferase (ALT) and Aspartate Aminotransferase (AST) are the most important representatives of a group of enzymes which catalyse the conversion of alpha-keto acids into amino acids by transfer of amino groups.

Alanine aminotransferase is an enzyme found predominantly in the liver but smaller amounts are also found in the kidneys, heart and muscles. Under normal conditions levels of ALT in the blood are low but when the liver is damaged ALT is released into the blood stream and can usually be detected before other symptoms of liver damage such as jaundice occur.  Serum ALT, sometimes known as serum glutamic-pyruvic transaminase (SGPT) can help with the diagnosis and monitoring of liver disorders.

Aspartate Aminotransferase (AST) is an enzyme found predominantly in heart and liver and to a lesser extent in other muscles. Measuring serum Aspartate Aminotransferase (AST) also known as serum glutamic-oxalacetic transaminase (SGOT) can be assistance when diagnosing liver disorders and may also be indicative of myocardial infarction, myscle dystrophy or organ damage.

Aminotransferase enzymes can indicate the degree of liver inflammation and elevated levels are seen in hepatitis.   ALT and AST are usually measured together as different ratios of AST:ALT are associated with Wilsons disease, alcoholic liver disease and non alcoholic steatohepatitis.

ALP and GGT for Bile Duct Disorders

Alkaline Phosphatase (ALP) is an enzyme found in the liver and biliary tract. Enzyme levels are dependent upon age and sex and increase during bone growth in childhood and in pregnancy. Pathological increases in ALP activity is observed in hepatitis, cirrhosis, malignant tumours and bone diseases.  ALP may be of interest to those investigating reproduction, child development, liver disease, bone disease or cancer.

Gamma GT (gamma glutamyltransferase) (GGT) is an enzyme found in high concentrations in renal tissue. In patients with hepatobiliary diseases significant levels of Gamma GT are found in the serum. This hepatic enzyme appears sooner than other enzymes and remains in the plasma for a longer time making its measurement a valuable tool in the diagnosis of such diseases.

ALP and GGT are often measured together and increases in both of these enzymes are seen in cases of obstructive of cholestatic liver disease where bile is not properly transported from the liver due to a blockage of the bile ducts.  Measuring an increase in GGT will also help to confirm that the rise in serum ALP originates from liver injury.

GLDH for Perivenular Hepatocyte Damage

Glutamate dehydrogenase (GLDH) is a mitochondrial enzyme that catalyses the conversion of glutamate to 2-oxoglutarate. Whilst glutamate dehydrogenase (GLDH) is found in many tissues throughout the body, serum GLDH originates mainly from hepatocytes in the liver.

GLDH is concentrated in the mitochondria of perivenular hepatocytes and increased serum GLDH is indicative of damaged or necrotic hepatocytes.  Drug and toxin induced liver damage may affect distinct zones within the organ, Perivenular liver damage resulting Ethanol, tetracarbon monochloride or hypoxia induced perivenular liver damage is associated with increased serum GLDH.

Bile Acids Tests

  • Kinetic, enzymatic recycling method
  • Use with serum or plasma
  • Suitable for automation
  • Ready-to-use reagents
  • OVS 30 days at 2-8ºC
  • Linearity up to 180µmol/L

Bilirubin Assays

Diazo methods for determination of Bilirubin have traditionally been widely used but are prone to interference from haemoglobin, which may result in under reporting, or ascorbic acid which can falsely elevate the test result. The Wako Direct and Total Bilirubin assays use a vanadation oxidation principle and offer excellent performance with minimal interference – giving clear, reliable answers when it matters.

  • No interference from Ascorbic Acid up to 50 mg/dL
  • No interference from Haemoglobin up to 500mg/dL
  • Ready-to-use reagents
  • OVS 30 days at 2-8ºC
  • Direct Bilirubin: linear to 20mg/dL
  • Total Bilirubin: linear up to 40 mg/dL

Hyaluronic Acid Assay

Percutaneous liver biopsy is considered the gold standard for diagnosis and staging liver disease.  However, this invasive procedure is costly and can be problematic, sample limitation may not give conclusive results and the procedure can result in pain, bleeding or even patient death.  Serum Hyaluronic Acid is the current biomarker of choice for liver fibrosis presenting a cost-effective way to distinguish between cirrhosis and earlier stages of fibrosis. Using a cut-off concentration of 60 ng/ml, HA typically shows a negative predictive value of up to 100% and a positive predictive value of 61% for cirrhosis.

The introduction of the Wako HA LT kit means that the Hyaluronic Acid Assay can be automated in the routine clinical laboratory for the first time. In the Assay, the HA in the sample combines with Hyaluronic Acid Binding Protein (HABP). An insoluble aggregate is then made by adding latex particles, coated with anti-HABP antibody. The resulting increase in turbidity is proportional to the concentration of Hyaluronic Acid in the sample.

  • Use serum or plasma samples
  • Ready-to-use reagents
  • Linearity up to 1000 ng/ml
  • No interference from ascorbic acid, bilirubin or haemoglobin

Aminotransferase Enzyme Assays

  • Ready-to-use reagents
  • On board stability 30 days
  • Calibration interval 14 days
  • Use with serum or plasma
  • Assay range 2-300 u/L ALT
  • Assay range 2-300 u/L AST

ALP and GGT Assays

  • Ready-to-use reagents
  • On board stability 30 days
  • Calibration interval 14 days
  • Use with serum or plasma
  • Assay range 6-700 U/L ALP
  • Assay range 2-700 U/L GGT

GLDH Test

  • Kinetic, DGKC method
  • Use with serum or plasma
  • Suitable for automation
  • Ready-to-use reagents
  • Linearity up to 120 U/L

 

  • A Direct Bilirubin Method fit for a King(ston)

    • PDF size: 10.80KB
    • Uploaded on: 02/09/2016

    Kingston Hospital evaluation of the Wako vanadate oxidation Direct Bilirubin method.

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  • Bilirubin Assay User Reports in Leading Edge

    • PDF size: 13.07KB
    • Uploaded on: 02/09/2016

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  • Bilirubin: Vanadate Oxidation Method

    • PDF size: 10.60KB
    • Uploaded on: 02/09/2016

    Bilirubin Flyer

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  • Hyaluronic Acid Automated Assay

    • PDF size: 12.57KB
    • Uploaded on: 21/09/2015

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  • Hyaluronic Acid Clinical Overview

    • PDF size: 11.56KB
    • Uploaded on: 21/09/2015

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