P.O. Box 3003
Dryden, ON P8N 2Z6
Phone: (807) 223-8264
Fax : (807) 223-7342
e-mail: alrobinson@dh.dryden.on.ca
Newsletter
2007-01
Screening Tests for Possible Liver Disease
Background: The widespread availability and use of serum blood chemistries for screening both
symptomatic and asymptomatic patients has resulted in a dramatic increase in the number of normal
and abnormal liver chemistry tests that must be interpreted by physicians. Therefore, a rational
approach for the appropriate evaluation of serum liver chemistries is essential for providing highquality, cost-effective health care. The following guidelines were developed to assist the primary care
physician, by the American Gastroenterological Association, to provide a rational approach for the
interpretation and further diagnostic evaluation of patients with abnormal liver chemistry tests.
Indications: Laboratory tests generally are effective in detecting hepatic dysfunction, assessing the
severity of liver injury, refining the diagnosis concerning any identified abnormalities, monitoring the
course of liver disease, and evaluating the response to treatment. Many tests of liver biochemistry and
excretory performance are called liver function tests. This is a misnomer as some of these tests,
rather than assessing liver function, assess liver necrosis or injury by measuring liver enzymes released
into the bloodstream (eg. aminotransferase). Only some liver function tests actually assess liver
function by evaluating hepatobillary excretion (eg. bilirubin) or the liver’s synthetic capability [eg. PT
(usually reported as the INR)].
Tests that detect liver inflammation, altered immunoregulation, or viral hepatitis include hepatitis
serology, immunoglobulins, antibodies and autoantibodies. These tests reflect B lymphocyte rather
than hepatocyte function. Other laboratory tests may reflect specific disorders, such as alpha
fetoprotein in hepatocellular carcinoma. All of these are not screening tests but can indicate etiology
directed by the patient’s history.
Limitations: The interpretation of all abnormal liver chemistries must be taken in context. This
should include an assessment of the patient’s risk factors for liver disease, medications, alcohol
consumption, comorbid conditions, and signs and symptoms of hepatic disease.
Aminotransferases: ALT and AST are indicators of liver cell injury, however, ALT is more specific. AST
can also be elevated in tissue injury to other organs. The ratio of AST/ALT has some clinical utility but
has important limitations. In 2005, the KRR RLP recommended AST be discontinued for the assessment
of cardiac and liver function.
Newsletter
2007-01
LDH: Lactate dehydrogenase (LDH or LD) is an enzyme that is found in almost all body tissues. When
cells are damaged or destroyed, however, they release LDH into the bloodstream, causing blood levels
to rise. For this reason, LDH is a general marker of injury to cells; it is not useful for determining
which specific cells are damaged.
Like AST, testing on site has been discouraged.
Bilirubin:
Bilirubin is the pigment in bile produced from the breakdown of heme proteins.
Hyperbilirubinemia results from increased bilirubin production, decreased liver uptake or conjugation,
or decreased biliary excretion.
Alkaline Phosphatase:
The primary importance of Alkaline phosphatase in detecting hepatic
dysfunction is to detect hepatobiliary disease. A blockage of the bile ducts will raise the Alkaline
phosphatase in the blood. This enzyme is sensitive but not specific to hepatobiliary disease.
Serum albumin: This is commonly decreased in chronic liver disease because of an increase in
volume of distribution (eg. due to ascites), a decrease in hepatic synthesis, or both. Alcoholism,
chronic inflammation and protein malnutrition also depress albumin synthesis. Because albumin has a
half-life of about 20 days, serum levels may take weeks to increase or decrease.
PT/INR: The PT or INR is a valuable measure of the liver’s ability to synthesize Vitamin K-dependent
clotting factors.
Abnormalities indicate severe hepatocellular dysfunction (ie. Acute liver disease) in chronic liver
disease, a rising PT or INR indicates progression to advanced cirrhosis. The PT or INR does not increase
In mild hepatocellular dysfunction and is often normal in cirrhosis.
y-Glutamyl transpeptidase (GGT): Levels of this enzyme rise in hepatobiliary disease, especially
cholestasis, and correlate loosely with levels of alkaline phosphatase. It is not as sensitive as Alkaline
Phosphatase but more specific. Levels do not increase with bone lesions, during childhood, or during
pregnancy. However, levels increase with induction of microsomal enzymes (eg. by ingesting dertain
drugs, such as anticonvulsants, and particularly in alcoholics), limiting its specificity. An elevated y-GT
confirms that an elevated Alkaline Phosphatase is of liver origin.
Further Reading:
1. American Gastroenterological Association, American Gastroenterological Association Medical
Position Statement: Evaluation of Liver Chemistry Tests. Gastroenterology 2002/123: 13641366.
2. British Columbia Health Services: http://www.health.gov.bc.ca/gpac/pdf/liver.pdf
Newsletter
2007-01
References:
1. American Gastroenterological Association, American Gastroenterological Association Medical
Position Statement: Evaluation of Liver Chemistry Tests. Gastroenterology 2002/123: 13641366.
2. Merck Manual, Testing for Hepatic and Biliary Disorders. November, 2005. www.merck.com
Dr. MacDonald would be pleased to discuss these guidelines with you at his next onsite visit.
We’d like to hear from you!!
Was this article helpful? Are there other topics you would like information on?
Let us know by contacting your Laboratory Manager or,
Anna Robinson
Regional Laboratory Consultant
Kenora-Rainy River Regional Laboratory Program, Inc.
P.O. Box 3003, Dryden, ON P8N 2Z6
Phone: 807-223-8264 Fax: 807-223-7342
e-mail: alrobinson@dh.dryden.on.ca