Elevated Preoperative Serum Gamma-glutamyltranspeptidase Predicts Poor Prognosis for Hepatocellular Carcinoma after Liver Transplantation

Abstract

Gamma-glutamyltransferase (γ-GGT) is a membrane-bound enzyme that is involved in biotransformation, nucleic acid metabolism, and tumourigenesis. Elevated serum γ-GGT levels are related to an increased cancer risk and worse prognosis in many cancers. In the present study, we evaluated the prognostic value of preoperative serum γ-GGT in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). A total of 130 HCC patients after LT were included in the study. The optimal cut-off value of γ-GGT was 128U/L by receiver operating characteristic analysis, with a sensitivity and specificity of 60.0% and 72.9%, respectively. Elevated preoperative serum γ-GGT was significantly associated with high alpha-fetoprotein (AFP), large tumor size, and macro- and micro-vascular invasion. The 1-, 3-, 5-year disease-free survival (DFS) and overall survival (OS) rates of HCC patients in the γ-GGT > 128U/L group were poorer than those in the γ-GGT ≤ 128U/L group. Stratification analysis revealed that γ-GGT exhibited a greater predictive value for DFS and OS in HCC patients beyond the Milan criteria and no macro-vascular invasion. In conclusion, elevated preoperative serum γ-GGT was significantly associated with advanced tumor stage and aggressive tumor behaviors, and serum γ-GGT can be considered as a prognostic factor for HCC patients after LT, especially for patients beyond the Milan criteria or without macro-vascular invasion.

Figure 1. Receiver operating characteristic curves for the determination of the cut-off value for preoperative serum γ-GGT in patients with HCC after liver transplantation.

Figure 2

Kaplan-Meier survival curves demonstrating that patients with γ-GGT ≤ 128 U/L exhibited shorter DFS (A) and OS (B) rates than those with γ-GGT > 128 U/L (all P < 0.001, log-rank).

Figure 3

Kaplan-Meier survival curves demonstrating that patients with γ-GGT > 128 U/L exhibited shorter DFS (A) and OS (B) rates than those with γ-GGT ≤ 128 U/L in the no macro-vascular invasion subgroup (A: P = 0.034; B: P = 0.002, log-rank).

Figure 4

Kaplan-Meier survival curves demonstrating that patients with γ-GGT ≤ 128 U/L exhibited longer DFS (A) and OS (B) rates than those with γ-GGT > 128 U/L in the beyond the Milan criteria subgroup (A: P = 0.006; B: P = 0.012, log-rank).