Effects of various interventions on the occurrence of macrovascular invasion of hepatocellular carcinoma after the baseline serum γ-glutamyltransferase stratification

Abstract

Background: Elevated serum γ-glutamyltransferase (γ-GT) levels are related to an increased cancer risk and worse prognosis in many cancers. We evaluated the effects of γ-GT stratification on the occurrence of macrovascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) who underwent hepatic resection (HR), transcatheter arterial chemoembolization (TACE), or TACE combined with radiofrequency ablation (TACE-RFA).

Patients and methods: A total of 903 patients with HCC in Barcelona Clinic Liver Cancer Stage A or B were included. Of these patients, 118 underwent HR, 445 underwent TACE-RFA, 256 underwent TACE, and 84 patients received conservative treatment only (control group). γ-GT, albumin, α-fetoprotein, and intervention were selected as significant predictive factors for MVI in 1 year by forward selection. The optimal cutoff value of γ-GT was 39 IU/L according to receiver operating characteristic analysis, with a sensitivity and specificity of 87.0% and 45.6%, respectively.

Results: The 1-year MVI incidence of patients with HCC in the group with γ-GT ≥39 IU/L was higher than that of the group with γ-GT <39 IU/L treated with HR, TACE-RFA, or TACE (P=0.0166, P=0.0041, and P<0.001, respectively). The MVI rates at 1 year were similar in the group with γ-GT ≥39 IU/L that underwent HR, TACE-RFA, or TACE and the control group (P=0.4402, P=0.2214, and P=0.4159, respectively). Different effects of various treatments with γ-GT <39 IU/L group on the occurrence of MVI are not significant (P=0.5167). However, the incidence of MVI after TACE was significantly higher than that after HR or TACE-RFA in γ-GT ≥39 IU/L group (P=0.0253).

Conclusion: Baseline serum γ-GT stratification may help select the appropriate treatment to reduce the MVI incidence.

Keywords: gamma-glutamyltransferase; liver cancer; macroscopic vascular invasion.

Figure 1

ROC curves for variables shown to be associated with MVI in multivariate analysis. Note: The area under the curve of γ-GT developed in the study was greater than that of other predictive indicators. Abbreviations: AFP, α-fetoprotein; ALB, albumin; AUROC, area under ROC; γ-GT, γ-glutamyltransferase; MVI, macrovascular invasion; ROC, receiver operating characteristics.

Figure 2

Kaplan–Meier analysis for the incidence of MVI after different interventions. Notes: Kaplan–Meier survival curves demonstrating that patients with γ-GT <39 IU/L exhibited lower 1-year MVI rates than those with γ-GT ≥39 IU/L after (A) HR, (B) TACE-RFA, or (C) TACE (P=0.0147, P=0.0017, and P<0.001, respectively). Abbreviations: γ-GT, γ-glutamyltransferase; HR, hepatic resection; MVI, macrovascular invasion; TACE, transcatheter arterial chemoembolization; TACE-RFA, TACE combined with radiofrequency ablation.

Figure 3

The MVI incidences after the γ-GT stratification. Notes: Kaplan–Meier survival curves demonstrating that the difference in the effects of various treatments in γ-GT <39 IU/L group (A) on the occurrence of MVI was not significant (P=0.5167). In γ-GT ≥39 IU/L group (B), the incidence of MVI after TACE was significantly higher than those after HR or TACE-RFA (P=0.0253). Abbreviations: γ-GT, γ-glutamyltransferase; HR, hepatic resection; MVI, macrovascular invasion; TACE, transcatheter arterial chemoembolization; TACE-RFA, TACE combined with radiofrequency ablation.

Figure 4

The MVI incidences of BCLC A and B stage. Notes: Kaplan–Meier survival curves demonstrating that patients with γ-GT <39 IU/L exhibited lower 1-year MVI rates than those with γ-GT ≥39 IU/L in the BCLC A stage after (A) HR, (B) TACE-RFA, or (D) TACE, and (E) in the BCLC B stage after TACE (P=0.0067, P=0.0060, P=0.0464, and P=0.0017, respectively); the MVI rates were similar at 1 year for patients with γ-GT <39 IU/L and γ-GT ≥39 IU/L in the BCLC B stage after (C) TACE-RFA (P=0.4033). Abbreviations: BCLC, Barcelona Clinic Liver Cancer; γ-GT, γ-glutamyltransferase; HR, hepatic resection; MVI, macrovascular invasion; TACE, transcatheter arterial chemoembolization; TACE-RFA, TACE combined with radiofrequency ablation.