Gamma-glutamyl transpeptidase (GGTP) was first reported as a potential marker for liver disease in 1961. Cohen and McNamara, in the first study to do so, sought to understand the utility of GGTP in children with liver disease. The authors enrolled 41 participants with known liver disease and 74 control participants with no signs/symptoms of liver disease. They found that serum GGTP levels were higher in the participants with known hepatic disease. Furthermore, when the investigators compared GGTP levels in patients with hepatitis vs. those with cirrhosis, they found higher GGTP levels in the cirrhotic patients. The authors postulated that the difference in relative GGTP elevation could be explained by chronic scarring. That is, in patients with cirrhotic disease, the scarring process causes an elevation of GGTP.
We now know gamma-glutamyltransferase (GGT) is a microsomal enzyme located in the bile canaliculi as well as the heart, lungs, pancreas and seminal vesicles.(1) In children, GGT is a more sensitive measure of biliary obstruction or biliary disease than alkaline phosphatase (ALP) because ALP can vary with age. Importantly, GGT reference ranges change with age. The normal range is higher in the neonatal period and declines to adult ranges by about 5–7 months.
GGT can be a useful laboratory test in the work up of neonatal cholestasis. An elevated GGT could indicate extrahepatic biliary disease such as biliary atresia(1) and a low GGT could indicate the presence of intrahepatic cholestasis (e.g. PFIC 1, PFIC 2). GGT is also useful in children who have undergone liver transplantation and could indicate acute cellular rejection or biliary complications.(1) Elevated GGT levels can be seen with a number of drugs and may not represent liver disease; therefore caution is advised when interpreting an elevated GGT.
We are grateful to Cohen and McNamara for their contribution in establishing that GGTP is a useful biomarker to differentiate children with and without liver disease. Given how frequently GGT is obtained in a tertiary pediatric liver clinic, it’s easy to forget that this laboratory test was first studied in pediatrics only 50 years ago.
Footnotes
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References
- 1.Cabrera-Abreu JC, Green A. Gamma-glutamyltransferase: value of its measurement in paediatrics. Ann Clin Biochem. 2002;39(Pt 1):22–5. [DOI] [PubMed] [Google Scholar]