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Sunday, June 27, 2010

Gamma-glutamyl Transferase

Gamma-glutamyl transferase, abbreviated GGT, is a sensitive indicator of liver disease. While an increased value of GGT can indicate the presence of liver damage it cannot be used to pinpoint a condition causing the damage. Because it is nonspecific for liver damage it is used in conjunction with other liver enzymes such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). In some instances it is used together with ALP to determine if an elevated ALP is due to liver or bone disease.

Gamma-glutamyl transferase is an enzyme found in cells that acts upon peptides and compounds that contain a gamma-glutamyl group. It transfers the gamma-glutamyl group from these peptides and compounds to a different acceptor. GGT is found in all cells throughout the body with the exception of myocytes. The highest concentration of GGT levels are found in the kidneys and the liver. A serum GGT level is reflective mainly of liver GGT and has a half life of around four days. Both GGT and ALP are enzymes bound to the membranes of cells. While ALP can be found in both liver and bone cells, GGT is found in its greatest concentration within hepatocytes. When a liver becomes diseased it begins to produce more GGT and ALP, thus they are both good indicators of hepatic dysfunction.

GGT serum levels rise during various disease states. The highest elevations can be found in the case of biliary obstructions. In order to determine whether or not the obstruction is intra-hepatic versus post-hepatic a serum bilirubin can be run in conjunction with the GGT. An intra-hepatic obstruction will have only a small rise in the serum bilirubin whereas a post-hepatic obstruction will have a greatly elevated serum bilirubin. High concentrations of serum GGT can also be present in liver cancer and the GGT might be elevated even before other liver enzymes become elevated. Moderate elevations of serum GGT can be found in infectious hepatitis. Small increases in GGT can be found in fatty liver disease and drug or alcohol intoxication. Some of the drugs that can cause an elevated serum GGT include phenytoin, carbamazepine, phenobarbitol, steroids, and erythromycin. The most common liver aliment that presents with an elevated GGT is alcoholism. Acute ingestion of alcohol will cause a small elevation in serum GGT. This level will fall again as the liver processes the alcohol. When it comes to chronic alcoholics, about 75% will present with an elevated GGT that persists. In some cases disease states other than actual liver disease can cause GGT to be elevated. In the case of myocardial infarction and congestive heart failure it is believed that the lack of sufficient blood flow to the liver is enough to cause damage and elevate GGT levels. Pancreatitis and pancreatic cancer can also present with occasional elevated levels of GGT. In all cases it is important to evaluate GGT levels in conjunction with other laboratory values in order to determine a patient’s disease state.

The lab in which I work currently runs GGT on the DADE Dimension system. This test is a colormetric test that uses the reagents gamma-glutamyl-3-carboxy-4-niranilide (GCNA) and glycylglycine. If GGT is present in serum it acts as a catalyst and transfers the glutamyl group from GCNA to the molecule glycylglycine. During this transfer a molecule called 5-amino-2-nitrobenzoate is released and the concentration of this molecule is read at an absorbance of 405 nm. The amount of 5-amino-2-nitrobenzoate released is proportional to the concentration of GGT present in the serum. GGT levels are prone to interferences from hemolysis due to the presence of GGT in red blood cell membranes. Hemolysis will cause a false increase in GGT. High levels of bilirubin will also cause a GGT level to be falsely increased. Finally triglyceride levels over 60 mg/dL can cause a false decrease in GGT concentration. Normal ranges are age dependent and infants and children have higher levels than adults. For adults the normal range is around 5-85 U/L.
Gamma-glutamyl transferase is used by clinicians as indicator of liver disease. Since it is nonspecific for liver damage it should be used along side other liver enzymes to determine the presence of liver disease. Comparing GGT results alongside other liver enzymes can help a clinician better pinpoint the origin of disease in a patient. For instance running an ALP along side a GGT can help a clinician determine if a patient has bone disease versus liver disease. Also running a bilirubin and liver panel alongside a GGT can help a clinician determine if an obstruction in the gastrointestinal tract is pre-hepatic or post-hepatic. Although it is a very little used test in the laboratory it is still a valuable tool that laboratory technicians can offer to clinicians for the purpose of diagnosing patients.


References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 458, 612-613,1797.
• GGT. (2010). GGT: The Test. Lab Tests Online. Retrieved on March 21, 2010 from http://www.labtestsonline.org/understanding/analytes/ggt/test.html
• SIEMENS Dimension Flex reagent cartridge. (2008). GGT. (REF DF45A). Newark, DE: Siemens Healthcare Diagnostics Inc.
• GGT. (2000). SydPath: GGT. SydPath: The Institute of Laboratory Medicine. Retrieved on March 21, 2010 from http://www.sydpath.stvincents.com.au/ tests/GGT.htm

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