The Significance of Gamma-Glutamyl Transpeptidase to Lymphocyte Count Ratio in the Early Postoperative Recurrence Monitoring and Prognosis Prediction of AFP-Negative Hepatocellular Carcinoma

Abstract

Background: Currently, there is still a lack of effective biomarkers for the recurrence monitoring and survival prognosis assessment of hepatocellular carcinoma (HCC) patients with alpha-fetoprotein (AFP)-negative (≤20 ng/mL) after radical resection.

Methods: The clinicopathological data of 606 patients (303 in the AFP-negative group and 303 in the AFP-positive group) who underwent radical resection of HCC were analyzed retrospectively.

Results: The gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) of patients in the AFP-negative group was lower than that in the AFP-positive group (p <0.001). The GLR level of the early-recurrence group was higher than that of the non-early-recurrence group (p =0.003). GLR had fair accuracy in predicting the early-recurrence of HCC patients [c-index=0.654 (95% CI=0.606-0.702); AUC=0.681 (95% CI=0.625-0.733)]. Univariate analysis showed that patients with tumor size <5 cm, no microvascular invasion, single tumor, no metastasis, BCLC stage 0-A, no recurrence, and GLR ≤45.0 had longer disease-free survival (DFS) and overall survival (OS) among AFP-negative HCC patients. In addition, multivariate Cox proportional hazards regression analysis showed that tumor size <5 cm (p =0.003), no recurrence (p <0.001), and GLR <45.0 (p <0.001) were independent predictors of longer OS.

Conclusion: GLR may be a potential indicator for early recurrence monitoring and prognosis evaluation in HCC patients with AFP-negative after radical resection.

Keywords: AFP-negative; GLR; early-recurrence; hepatocellular carcinoma; prognosis.

Figure 1

Flow chart showing the inclusion process of eligible patients in the study.

Figure 2

The role of GLR in the prediction and evaluation of early recurrence in different groups of HCC. (A) The scatter plot showed the difference in GLR level between the early-recurrence group and the non-early-recurrence group. (B) The ROC curve was performed to assess the role of GLR in predicting early recurrence of HCC.

Figure 3

The relationship of GLR level with recurrence rate and OS in AFP-negative HCC patients. Kaplan–Meier analysis revealed a significantly higher recurrence rate (A) and shorter OS (B) in AFP-negative HCC patients with GLR ≤45.0 than in those with GLR >45.0. The OS of AFP-negative patients was longer than that of AFP-positive patients (C). The OS of patients with GLR ≤45.0 was longer than that of patients with GLR >45.0 (D). The postoperative recurrence rate of AFP-negative patients was highest in the GLR >45.0 and TS >5 cm group, and lowest in the GLR ≤45.0 and TS ≤5 cm group (E), while the OS of patients was lowest in the GLR >45.0 and TS >5 cm group, and highest in the GLR ≤45.0 and TS ≤5 cm group (F).