Novel Value of Preoperative Gamma-Glutamyltransferase Levels in the Prognosis of AFP-Negative Hepatocellular Carcinoma

BACKGROUND: Gamma-glutamyltransferase (GGT) is involved in tumor development and progression, but its prognostic value in α-fetoprotein- (AFP-) negative (AFP < 25 ng/mL) hepatocellular carcinoma (HCC) patients remains unknown. METHODS: A large cohort of 678 patients with AFP-negative HCC following curative resection who had complete data were enrolled in this study. The optimal cutoff value for the preoperative level of GGT was determined by the X-tile program. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were also identified. RESULTS: The optimal cutoff values for the preoperative levels of GGT were 37.2 U/L and 102.8 U/L, which were used to divide all patients into three subgroups (group 1, GGT < 37.2 U/L (n = 211, 31.1%); group 2, GGT ≥ 37.2 and <102.8 U/L (n = 320, 47.2%); group 3, GGT ≥ 102.8 U/L (n = 147, 21.7%)), with distinct OS times (58.5 vs. 53.5 vs. 44.4 months, P < 0.001) and DFS times (47.9 vs. 40.3 vs. 30.1 months, P < 0.001). Elevated preoperative GGT levels were associated with an unfavorable tumor burden (larger tumor size, multiple tumors, and microvascular invasion) and were selected as independent predictors of a worse OS (group 2 vs. group 1, HR: 1.73 (1.13-2.65), P = 0.011; group 3 vs. group 1, HR: 3.28 (2.10-5.13), P < 0.001) and DFS (group 2 vs. group 1, HR: 1.52 (1.13-2.05), P = 0.006; group 3 vs. group 1, HR: 2.11 (1.49-2.98), P < 0.001) in multivariable analysis. CONCLUSIONS: Elevated preoperative GGT levels are associated with an unfavorable tumor burden and serve as an independent prognostic marker for worse outcomes in AFP-negative HCC patients following resection.