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

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.