Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

Abstract

Aim: To investigate novel predictors of survival in hepatocellular carcinoma (HCC) patients following transarterial chemoembolization (TACE).

Methods: One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results (total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index (AgI). We used The Wilcoxon rank-sum (Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival.

Results: The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56 (95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase (GGTP) had ORs of 1.01 (95%CI: 1.003-1.026, P < 0.017) and 0.99 (95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18 (95%CI: 1.108-4.310, P < 0.024). GGTP's single unit change had a HR for mortality of 1.003 (95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26 (95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003 (95%CI: 1.001-1.004, P < 0.001).

Conclusion: Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.

Keywords: Aggressiveness index; Hepatocellular carcinoma; Liver function; Survival; Transarterial chemoembolization.

Figure 1

Kaplan-Meier survival plots between categories of aggressiveness Index, in total cohort. Aggressiveness index as sum of scores, MTD (in tertiles): MTD < 4.5; 4.5 ≤ MTD ≤ 9.6; MTD > 9.6; scores 1, 2, 3 respectively; AFP (cut-off): AFP < 100; 100 ≤ AFP ≤ 1000; AFP > 1000 ng/mL; scores 1, 2, 3 respectively; PVT (no/yes): PVT (no); PVT (yes); scores 1, 3 respectively; Tumor nodules (number): Nodules ≤ 3; nodules > 3; scores 1, 3 respectively. ¹Wilcoxon (breslow) test. MTD: Maximum tumor diameter; AFP: Alpha-fetoprotein; PVT: Portal vein thrombosis.

Figure 2

Scatterplots between maximum tumor diameter (cm) and gamma glutamyl transpeptidae (IU/mL) (Spearman's rho = 0.2604, P = 0.0012), together with linear regression line of gamma glutamyl transpeptidae on maximum tumor diameter, in total cohort. All transformed into natural logarithm. ln, natural logarithm; Fitted values (-------).