Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma

Abstract

Background: Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC.

Methods: We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups.

Results: During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05). GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival.

Conclusion: The GPR is an effective preoperative predictor for outcomes in hepatitis B-associated HCC.

Keywords: GPRs; cirrhosis; gamma-glutamyl transpeptidase; hepatitis B virus; hepatocellular carcinoma; platelets; survival.

Figure 1

Diagnostic performance of GPR, S-index, and contained variables in detecting the presence of cirrhosis. Abbreviations: ALB, albumin; GGT, gamma-glutamyl transpeptidase; GPR, gamma- glutamyl transpeptidase to platelet ratio; PLT, platelet count; ROC, receiver operating characteristic.

Figure 2

The box plots reflect the associations between GPR and tumor size (A and B) and between S-index and Child–Pugh stage (C and D). Notes: Scatter plot (C) reflects the associations between GPR and tumor size, and the diagnostic performance of S-index (D) in detecting the Child-Pugh B/C stage. The P-values in (A) and (C) were calculated by Wilcoxon test. Abbreviations: GPR, gamma-glutamyl transpeptidase to platelet ratio; ROC, receiver operating characteristic.

Figure 3

Kaplan–Meier cumulative overall survival and recurrence-free survival curves of patients stratified according to the GPR (A, B), S-index (C, D), and BCLC stage (E, F). Note: The P-values were calculated by log-rank test. Abbreviations: BCLC, Barcelona Clinic Liver Cancer; GPR, gamma-glutamyl transpeptidase to platelet ratio.

Figure 4

Forest plot based on the results of multivariate analysis of the factors associated with overall survival and recurrence-free survival of hepatitis B-related HCC patients. Note: The factors that were found to be significant (P<0.05) in univariate analysis were entered into a multivariate Cox regression models. Abbreviations: AFP, alpha-fetoprotein; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; GPR, gamma-glutamyl transpeptidase to platelet ratio; HCC, hepatocellular carcinoma; HR, hazard ratio.

Figure 5

Forest plots based on the results of subgroup analyses of the GPR for overall survival (A) and recurrence-free survival (B) in patients with hepatitis B-related HCC. Note: The subgroup analyses were based on the following variables: age, level of AFP, status of cirrhosis, ascites, tumor size, tumor number, vascular invasion, BCLC stage, and treatment method. Abbreviations: AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; CI, confidence interval; GPR, gamma-glutamyl transpeptidase to platelet ratio; HCC, hepatocellular carcinoma; HR, hazard ratio; RFA, radiofrequency ablation.

Figure 6

Cumulative overall survival (A) and recurrence-free survival (B) curves of the subgroup study stratification of patients according to GPR and tumor size. Notes: Group A (GPR <0.76 and tumor size <5 cm), Group B (GPR <0.76 but tumor size ≥5 cm, or tumor size <5 cm but GPR ≥0.76), and Group C (GPR ≥0.76 and tumor size ≥5 cm). The P-values were calculated by log-rank test. Abbreviation: GPR, gamma-glutamyl transpeptidase to platelet ratio.