Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy

Abstract

Background: The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio (GPR) levels in patients with solitary hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) following radical resection has not been established.

Aim: To examine the clinical utility of GPR for prognosis prediction in solitary HBV-related HCC patients.

Methods: A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed. GPR levels were compared with 908 non-HCC individuals. Overall survival (OS) and recurrence-free survival (RFS) were evaluated, and cox proportional hazard model analyses were performed to identify independent risk factors. Differences in characteristics were adjusted by propensity score matching (PSM). Subgroup and stratified survival analyses for HCC risks were performed, and a linear trend of the hazard ratio (HR) according to GPR levels was constructed.

Results: GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas, chronic hepatitis B and healthy control (adjusted P < 0.05). Variable bias was diminished after the PSM balance test. The low GPR group had improved OS (P < 0.001) and RFS (P < 0.001) in the PSM analysis and when combined with other variables. Multivariate cox analyses suggested that low GPR levels were associated with a better OS (HR = 0.5, 95%CI: 0.36-0.7, P < 0.001) and RFS (HR = 0.57, 95%CI: 0.44-0.73, P < 0.001). This same trend was confirmed in subgroup analyses. Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction. Moreover, stratified survival analyses found that GPR > 0.6 was associated with a worse OS and higher recurrence rate (P for trend < 0.001).

Conclusion: Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBV-related HCC.

Keywords: Gamma-glutamyl transpeptidase to platelet ratio; Hepatitis B virus; Hepatocellular carcinoma; Prognosis; Propensity score matching.

Figure 1

Flow diagram of the propensity score analysis for this study. GPR: Gamma-glutamyl transpeptidase-to-platelet ratio; RCS: Restricted cubic spline; HCC: Hepatocellular carcinoma; BCLC: Barcelona Clinic Liver Cancer.

Figure 2

Violin plot analysis comparing the gamma-glutamyl transpeptidase-to-platelet ratio levels among hepatitis B virus-related hepatocellular carcinoma and other 7 non-hepatocellular carcinoma groups. Pairwise comparisons were performed by Games-Howell test, and P value was adjusted by Benjamini-Hochberg methods.

Figure 3

The balance test of propensity score matching and KaplanMeier analysis between gamma-glutamyl transpeptidase-to-platelet ratio level and prognosis of solitary hepatitis B virus-related hepatocellular carcinoma cohort. A: Distribution of propensity values before and after propensity score matching (PSM); B: Absolute standardized differences in covariates between solitary hepatocellular carcinoma (HCC) patients with gamma-glutamyl transpeptidase-to-platelet ratio (GPR) ≤ 0.2 and GPR > 0.2, before and after PSM; C and D: Kaplan-Meier survival curves of overall survival in patients with solitary HCC before and after PSM; E and F: Kaplan-Meier survival curves of RFS in patients with solitary HCC before and after PSM. PSM: Propensity score matching; GPR: Gamma-glutamyl transpeptidase-to-platelet ratio; BMI: Body mass index; HR: Hazard ratio; AFP: Alpha-fetoprotein; TB: Total bilirubin; ALB: Albumin; HBV: Hepatitis B virus; MVI: Microvascular imaging.

Figure 4

Subgroup analyses for gamma-glutamyl transpeptidase-to-platelet ratio level and combined analyses of gamma-glutamyl transpeptidase-to-platelet ratio levels and variables in overall survival and recurrence-free survival of solitary hepatitis B virus-related hepatocellular carcinoma. A: Subgroup analyses for overall survival (OS) and recurrence-free survival (RFS); B: Combined analyses with tumor size, cirrhosis, alpha-fetoprotein (AFP), and microvascular imaging (MVI) for OS; C: Combined analyses with tumor size, cirrhosis, AFP, and MVI for RFS. GPR: Gamma-glutamyl transpeptidase-to-platelet ratio; HR: Hazard ratio; OS: Overall survival; BMI: Body mass index; HR: Hazard ratio; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; BCLC: Barcelona Clinic Liver Cancer; F: Female; M: Male.

Figure 5

The association between gamma-glutamyl transpeptidase-to-platelet ratio and death/recurrence risk and Kaplan-Meier stratified analysis between gamma-glutamyl transpeptidase-to-platelet ratio levels and prognosis in the solitary hepatitis B virus-related hepatocellular carcinoma cohort. A: The restricted cubic spline curves of gamma-glutamyl transpeptidase-to-platelet ratio levels. The risk was adjusted by age, cirrhosis, hepatitis B virus-DNA, tumor size, microvascular imaging, and infiltrative growth; B: Kaplan-Meier survival curves of overall survival (OS) and recurrence-free survival (RFS) in patients with solitary hepatocellular carcinoma (HCC) before propensity score matching (PSM); C: Triangle plot and absolute standardized differences adjustment of three groups; D: Kaplan-Meier survival curves of OS and RFS in patients with solitary HCC after PSM. OS: Overall survival; PSM: Propensity score matching; GPR: Gamma-glutamyl transpeptidase-to-platelet ratio; MVI: Microvascular imaging; HBV: Hepatitis B virus; BCLC: Barcelona Clinic Liver Cancer; BMI: Body mass index; HR: Hazard ratio; AFP: Alpha-fetoprotein.

Figure 6

Prognostic nomograms for solitary hepatitis B virus-related hepatocellular carcinoma. A: Nomogram plot and calibration curves for overall survival; B: Nomogram plot and calibration curves for recurrence-free survival. AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; MVI: Microvascular imaging; BCLC: Barcelona Clinic Liver Cancer; GPR: Gamma-glutamyl transpeptidase-to-platelet ratio; RFS: Recurrence-free survival; OS: Overall survival; F: Female; M: Male.