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.

Upregulation of gamma-glutamyl-transpeptidase activity and uric acid level in mixed chemical exposure: implications for mutagenic and preneoplastic events

“…Gamma-glutamyl transpeptidase though an important member of the biologic detoxification system, like GST-P is poorly recognized , thus its evaluation as a potential biomarker along with uric acid, copper and the other parameters for the assessment of exposure to potentially deleterious chemicals and associated preneoplastic events appears desirable. The trend of increasing GGT levels with increasing duration of exposure observed in the present study is most probably a response to exposure to chemicals and not hepatic Substantial evidence now supports the view that induction of phase II enzymes (such as GGT) is a critical and sufficient mechanism for cellular protection against the toxic and carcinogenic actions of reactive intermediates, particularly in the liver (Alkozai et al, 2014) and generally at the cellular levels of tissues (Ayila et al, 2003). Secondly serum GGT levels even within normal reference range have recently been proposed as an early and sensitive marker of oxidative stress based on both experimental and epidemiological observations (Lee et al, 2004).…”

Electrochemical Methods for the Analysis of Clinically Relevant Biomolecules

“…GGT is a cell membrane-bound enzyme that catalyzes the transfer of the γ-glutamyl moiety of glutathione to an amino acid, a peptide, or water . Elevated serum GGT (>40 U L –1 ) is generally used as an indicator of liver disorders, such as biliary obstruction, alcohol toxicity, and exposure to certain drugs . Recently, several studies have demonstrated that higher serum GGT levels are associated with cardiovascular risk factors and certain types of cancer…”

Investigating the Causes for Decreased Levels of Glutathione in Individuals with Type II Diabetes

“…Extracellular GSH cannot be transported as a whole molecule into the cell. GGT, which is expressed on the cell membrane cleaves GSH at the γ-glutamyl linkage to release glutamine and cysteinyl glycine [ 16 , 17 ]. Cysteinyl glycine is then cleaved by aminopeptidase to cysteine and glycine.…”

“…Cysteinyl glycine is then cleaved by aminopeptidase to cysteine and glycine. Cystine is transported into the cells and is used as a reactant for the de novo synthesis of GSH [ 16 , 17 ].…”