Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival

Edris M Alkozai,Ton Lisman,Robert J Porte,Maarten W Nijsten

doi:10.12688/f1000research.3557

Abstract

Background: Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes. Aims : To study if and how GGT is correlated with mortality following liver transplantation. Methods: We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Results: Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p <0.0001. In contrast, late after transplantation, GGT levels were significantly lower in patients who survived more than 5 years than those who did not ( p <0.01). The pattern of GGT levels also differed from those of alanine aminotransferase, aspartate aminotransferase, and total bilirubin early after transplantation, while these patterns were congruent late after transplantation. Kaplan-Meier survival analysis showed that early after transplantation the higher the GGT levels, the better the 90-day survival ( p <0.001). In contrast, late after transplantation, higher GGT levels were associated with a lower 5-year survival ( p <0.001). Conclusions:  These paradoxical findings may be explained by the time-dependent role of GGT in glutathione metabolism. Immediate postoperative elevation of GGT may indicate a physiological systemic response while chronic elevation reflects a pathological response.

Highlights

Gamma glutamyl transpeptidase (GGT) is a membrane-bound enzyme that is essential for the synthesis of glutathione (GSH), a key antioxidant[1]
After excluding pediatric liver transplantation (LT), patients who were re-transplanted within the 90 days of their first LT (n=39), second or subsequent LTs (n=101), patients with a lack of follow up data (n=11), and patients that died intraoperatively (n=5) due to brain death, cardiac failure, or uncontrollable bleeding, 522 patients were included in our analyses
In this study, we evaluated the changes in GGT over time following liver transplantation and the clinical relevance of these changes for early and late survival

Summary

Introduction

Gamma glutamyl transpeptidase (GGT) is a membrane-bound enzyme that is essential for the synthesis of glutathione (GSH), a key antioxidant[1]. Several epidemiological studies have shown that a higher serum GGT level, even within the normal range, is associated with cardiovascular risk factors such as hypertension, hypertriglyceridemia, obesity, type 2 diabetes mellitus and stroke, as well as certain types of cancer[2,3,4,5,6,7,8,9,10] In contrast to these studies, we observed that after surgery for ruptured abdominal aortic aneurysm[11] or after liver resection[12], GGT is transiently increased in patients who had a good outcome. Immediate postoperative elevation of GGT may indicate a physiological systemic response while chronic elevation reflects a pathological response

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