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Background
The serum GGT is a shorthand abbreviation for a liver enzyme known as Gamma-glutamyltransferase. It is produced by the liver cell microsomes and is widely distributed in cells that are involved in the secretion and absorption of bile. It is a useful laboratory marker as an indicator of early liver cell damage or cholestatic disease. In the pediatric population, it is a useful marker to differentiate neonatal hepatitis from extrahepatic biliary atresia.
OUTLINE
Reference Methods Pediatric Clinical Utility Interfering Diseases or Substances that Alter Levels Commonly Used Terms Internet Links
CLINICAL UTILITY CHARACTERIZATION ALCOHOLISM
CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project.Conigrave KM, Degenhardt LJ, Whitfield JB, Saunders JB, Helander A, Tabakoff B; WHO/ISBRA Study Group.
Drug and Alcohol Department, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Sydney, Australia.
Alcohol Clin Exp Res 2002 Mar;26(3):332-9 Abstract quote BACKGROUND: Estimates of the performance of carbohydrate deficient transferrin (CDT) and gamma glutamyltransferase (GGT) as markers of alcohol consumption have varied widely. Studies have differed in design and subject characteristics. The WHO/ISBRA Collaborative Study allows assessment and comparison of CDT, GGT, and aspartate aminotransferase (AST) as markers of drinking in a large, well-characterized, multicenter sample.
METHODS: A total of 1863 subjects were recruited from five countries (Australia, Brazil, Canada, Finland, and Japan). Recruitment was stratified by alcohol use, age, and sex. Demographic characteristics, alcohol consumption, and presence of ICD-10 dependence were recorded using an interview schedule based on the AUDADIS. CDT was assayed using CDTect and GGT and AST by standard methods. Statistical techniques included receiver operating characteristic (ROC) analysis. Multiple regression was used to measure the impact of factors other than alcohol on test performance.
RESULTS: CDT and GGT had comparable performance on ROC analysis, with AST performing slightly less well. CDT was a slightly but significantly better marker of high-risk consumption in men. All were more effective for detection of high-risk rather than intermediate-risk drinking. CDT and GGT levels were influenced by body mass index, sex, age, and smoking status.
CONCLUSIONS: CDT was little better than GGT in detecting high- or intermediate-risk alcohol consumption in this large, multicenter, predominantly community-based sample. As the two tests are relatively independent of each other, their combination is likely to provide better performance than either test alone. Test interpretation should take account sex, age, and body mass index.
CYTOMEGALOVIRUS (CMV)
The postoperative course of gamma-glutamyl transpeptidase--a marker of cytomegalovirus (CMV) replication risk?Schenk M, Zipfel A, Kratt T, Petersen P, Becker HD, Viebahn R.
Department of General Surgery, University Hospital, Tubingen, Germany.
Clin Chem Lab Med 2000 Nov;38(11):1181-2 Abstract quote Cytomegalovirus (CMV) infection is a common complication in the postoperative course of liver transplantation. In order to start early prophylactic therapy, but to avoid unnecessary treatment, or expensive screening, a desirable goal in post-transplant monitoring is to find appropriate markers in standard laboratory diagnostics. In the present study, the results of a 6-week CMV replication monitoring schedule by the pp65 antigenemia assay in 100 liver graft recipients were included.
The activities of transaminases, glutamate dehydrogenase and gamma-glutamyl transpeptidase (gamma-GT) were measured by routine laboratory methods. In contrast to the transaminases, the serum activity of gamma-GT increased during the first postoperative week. The maximum levels were 246 +/- 211 U/l in patients without (n = 46) and 140 +/- 89 U/l in patients with early CMV replication (n = 54; p = 0.02). Patients with gamma-GT levels below 200 U/l on the 5th postoperative day (n = 72) had a CMV replication risk of 65%, whereas those patients with gamma-GT levels above this threshold had a risk of 30% (n = 28; p = 0.0007; relative risk = 2.9).
These findings provide a routinely usable marker for the identification of patients at an increased risk of CMV replication. It can be considered that these phenomena may be caused by an additional immunosuppressive effect of the CMV virus.
DIABETES MELLITUS
Gamma-glutamyltransferase and diabetes-a 4 year follow-up study.Lee DH, Ha MH, Kim JH, Christiani DC, Gross MD, Steffes M, Blomhoff R, Jacobs DR Jr.
Department of Preventive Medicine, College of Medicine, Kosin University, 34 Amnam-dong, Suh-gu, Pusan, Korea 602-702,
Diabetologia 2003 Mar;46(3):359-64 Abstract quote AIMS/HYPOTHESIS. Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes.
METHODS. A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication.
RESULTS. There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration.
CONCLUSION/INTERPRETATION. This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.
EXTRAHEPATIC BILIARY ATRESIA
Hepatic technetium-99m-mebrofenin iminodiacetate scans and serum gamma-glutamyl transpeptidase levels interpreted in series to differentiate between extrahepatic biliary atresia and neonatal hepatitis.Arora NK, Kohli R, Gupta DK, Bal CS, Gupta AK, Gupta SD.
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
Acta Paediatr 2001 Sep;90(9):975-81 Abstract quote Hepatic technetium-99m-mebrofenin iminodiacetate (99mTc-mebrofenin IDA) scans and serum gamma-glutamyl transpeptidase (GGTP) have high sensitivity for extrahepatic biliary atresia (EHBA).
This study was based on the hypothesis that the interpretation of results of 99mTc-mebrofenin IDA scans and serum GGTP levels in series would result in a reduction of the false positivity observed with these tests individually. The aetiology of neonatal cholestasis in 132 study patients was: 25% (33/132) EHBA, 45.5% (60/132) neonatal hepatitis (NH) with an identifiable cause and 19.7% (26/132) idiopathic NH.
Of the various clinical, biochemical and imaging parameters that were significantly different between patient groups, sensitivity for EHBA was: serum GGTP > or = 150 IU l(-1) (100%), 99mTc-mebrofenin IDA scans (100%), pale stools (82.8%) and total serum bilirubin > or = 12 mg dl(-1) (66%). However, specificity ranged from 48.5 to 79%. Of the 63 patients who had non-excreting IDA scans, operative cholangiograms could be avoided on the basis of a specific aetiological diagnosis of NH, made concurrently, in only 9 infants. The rest (54) underwent operative cholangiograms; 21 (39%) of these had patent biliary trees and therefore underwent the procedure unnecessarily. If serum GGTP (< 150 IU l(-1)) had been used as a screen after IDA scanning in these 54 patients, operative cholangiograms could have been avoided in another 12 patients and thereafter only 9/42 (21%) of the operative cholangiograms would have been considered unnecessary.
Conclusion: A diagnostic algorithm is proposed wherein serum GGTP level (at a cut-off level that maintains 100% sensitivity for EHBA) is used in series with non-excreting 99mTc-mebrofenin IDA scans (for patients with no specific aetiological label). This strategy reduces the false positivity of individual tests.
Value of gamma-glutamyl transpeptidase for early diagnosis of biliary atresia.Liu CS, Chin TW, Wei CF.
Department of Surgery, Veterans General Hospital-Taipei, National Yang-Ming University School of Medicine, Taiwan, ROC.
Zhonghua Yi Xue Za Zhi (Taipei) 1998 Dec;61(12):716-20 Abstract quote BACKGROUND: Early diagnosis of congenital biliary atresia (BA) is important because the prognosis is closely related to timing of a hepaticoportoenterostomy. In this study, we discuss whether the elevation of serum gamma-glutamyl transpeptidase (GGT) is accurate for the early differentiation of BA from neonatal hepatitis (NH).
METHODS: The effectiveness of using GGT before the age of 10 weeks and other tools in the differential diagnosis of BA and NH were analyzed retrospectively by reviewing the charts of 29 BA and 12 NH patients. The results of serial liver enzyme studies, abdominal sonography, hepatobiliary scintigraphy and transcutaneous liver biopsy were compared between both groups.
RESULTS: The peak GGT value in BA before 10 weeks of age was significantly higher than that in NH (622.5 +/- 211.9 U/l vs 168.8 +/- 100.3 U/l, respectively, p < 0.001). When a serum GGT concentration greater than 300 U/l was used as a diagnostic criterion for BA in patients younger than 10 weeks of age, the diagnostic accuracy was 85%. When an increase in GGT value (in serial measurements) of greater than 6 U/l/day was used as a criterion, the accuracy was 88%. The diagnostic accuracy of abdominal sonography, hepatobiliary scintigraphy and liver biopsy was 68%, 67% and 79%, respectively.
CONCLUSIONS: GGT concentration is diagnostically valuable when the results of other diagnostic methods are not available, or are controversial, in differentiating between BA and NH.
Diagnostic value of serum gamma-glutamyl transpeptidase activity in liver diseases in children.Maggiore G, Bernard O, Hadchouel M, Lemonnier A, Alagille D.
Unite de Recherche (INSERM U 56), Service d'Hepatologie Pediatrique, Kremlin-Bicetre, France.
J Pediatr Gastroenterol Nutr 1991 Jan;12(1):21-6 Abstract quote The clinical usefulness of serum gamma-glutamyl transpeptidase (gamma GT) assay for the diagnosis of liver disease in children was assessed retrospectively in 398 children investigated from 1981 to 1986, in whom diagnosis was ascertained according to currently accepted criteria including liver histology in each case.
Serum gamma GT activity was within normal limits in 10 controls, in 19 children with portal vein obstruction, and in 10 of 12 children with congenital hepatic fibrosis. Serum gamma GT was raised in all children with biliary atresia, sclerosing cholangitis, paucity of interlobular bile ducts, and alpha 1-antitrypsin deficiency with jaundice. Serum gamma GT was normal in spite of patent clinical signs of cholestasis in 3 patients with benign recurrent intrahepatic cholestasis, 1 infant with post-hemolytic neonatal cholestasis, and in 22 of 28 patients with progressive idiopathic cholestasis akin to Byler disease.
In the latter group, children with raised serum gamma GT displayed extensive portal fibrosis and bile duct proliferation on liver histology, while this was not a prominent feature in children with normal serum gamma GT.
These results indicate (a) the value and limits of the assay for serum gamma GT activity in children with liver disease, (b) that raised serum gamma GT may be considered a fairly reliable index of bile duct damage, and (c) that serum gamma GT may prove a useful tool in separating two forms of progressive idiopathic cholestasis, with or without bile duct involvement.
Gamma-glutamyl transpeptidase activity and its serial measurement in differentiation between extrahepatic biliary atresia and neonatal hepatitis.Fung KP, Lau SP.
J Pediatr Gastroenterol Nutr 1985 Apr;4(2):208-13 Abstract quote The liver functions of 17 babies with extrahepatic biliary atresia (EHBA) and 19 babies with neonatal hepatitis (NNH) were analyzed.
The serum gamma-glutamyl transpeptidase (GGTP) level and its rate of rise were significantly higher in the EHBA group. Both cross-sectional and longitudinal studies showed a positive correlation between the GGTP activity and the duration of the disease. The diagnostic accuracy is 79% for EHBA and 95% for NNH.
It is suggested that GGTP and its rate of rise are the most important biochemical parameters in the differential diagnosis of these two diseases.
STROKE
Gamma-glutamyltransferase and risk of stroke: the EUROSTROKE project.Bots ML, Salonen JT, Elwood PC, Nikitin Y, Freire de Concalves A, Inzitari D, Sivenius J, Trichopoulou A, Tuomilehto J, Koudstaal PJ, Grobbee DE.
Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.
J Epidemiol Community Health 2002 Feb;56 Suppl 1:i25-9 Abstract quote BACKGROUND: Alcohol consumption has been implicated in the aetiology of stroke. As data on alcohol consumption obtained by questionnaire are susceptible to misclassification, this study evaluated the association between gamma-glutamyltransferase (gamma-GT), as a marker for alcohol consumption, and fatal, non-fatal, haemorrhagic and ischaemic stroke in three European cohort studies, participating in EUROSTROKE.
METHODS: EUROSTROKE is a collaborative project among ongoing European cohort studies on incidence and risk factors of stroke. EUROSTROKE is designed as a nested case-control study. For each stroke case, two controls were sampled. Strokes were classified according to MONICA criteria or reviewed by a panel of four neurologists. At present, data on stroke and gamma-GT were available from cohorts in Cardiff (57 cases), Kuopio (66 cases), and Rotterdam (108 cases).
RESULTS: An increase in gamma-GT of one standard deviation (28.7 IU/ml) was associated with an age and sex adjusted 26% (95% CI 5 to 53) increase in risk of stroke. Adjustment for confounding variables such as drug use, history of myocardial infarction, total cholesterol, and diabetes mellitus did not materially attenuate the association. The risk of haemorrhagic stroke increased linearly with increase in gamma-GT. The association for cerebral infarction was not graded: the risk increased beyond the first quartile, and remained increased. The association of gamma-GT with stroke was significantly stronger among subjects without diabetes mellitus compared with subjects with diabetes mellitus (no association observed).
CONCLUSION: This EUROSTROKE analysis showed that an increased gamma-GT, as a marker of alcohol consumption, is associated with increased risk of stroke, in particular haemorrhagic stroke.
INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS CHARACTERIZATION
Sex differences in gamma-glutamyltransferase in people aged 40-42 years in two Norwegian counties.Skurtveit S, Tverdal A.
Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway.
Drug Alcohol Depend 2002 Jun 1;67(1):95-8 Abstract quote Gamma-glutamyltransferase (GGT) is widely used as a marker of alcohol intake, although it is documented that other factors are also associated with serum levels of GGT.
The total population of men and women aged 40-42 years in two Norwegian counties was invited to participate in a health survey program. GGT was measured in 8116 men and 8689 women--67 % of the eligible population. In sex-specific multiple regression analyses, GGT showed a positive association with body mass index (BMI), cholesterol, ln triglycerides, systolic blood pressure, and number of drinks per 2 weeks for both men and women. Glucose and 'years of smoking' were significant in women only. Cups of boiled coffee per day and physical activity in spare time were inversely associated with GGT level for both men and women.
A significant positive interaction between alcohol intake and BMI was observed for men but not for women. The use of GGT as a marker of alcohol consumption in middle-aged persons should take into account sex, BMI and drinking of boiled coffee.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
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