Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2018; 24(15): 1641-1649
Published online Apr 21, 2018. doi: 10.3748/wjg.v24.i15.1641
Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization
Yossi Ventura, Brian I Carr, Issac Kori, Vito Guerra, Oren Shibolet
Yossi Ventura, Oren Shibolet, Liver Unit, Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, Tel-Aviv 62431, Israel
Yossi Ventura, Oren Shibolet, Sackler faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
Brian I Carr, Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir 35340, Turkey
Issac Kori, Interventional Radiology, Division of Imaging Tel Aviv Medical Center, Tel-Aviv 62431, Israel
Vito Guerra, Department of Clinical Trials and Epidemiology, IRCCS de Bellis, Castellana Grotte 70013, Italy
Author contributions: All authors equally contributed to this manuscript.
Institutional review board statement: The Tel-Aviv medical center database management conforms to Israeli legislation on privacy and this study was approved by the institutional research committee in Tel-Aviv Medical Center (Approval number: 0528-16-TLV) in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent statement: Our manuscript is a retrospective study, therefore an informed consent waver was given by the IRB. Data was anonymized to prevent identification.
Conflict-of-interest statement: Professor Shibolet has nothing to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Consent was not obtained but the presented data are anonymized and there is no risk of patient identification. The potential benefits of sharing these data outweigh the potential harms because of its possible application in improving future identification and treatment of HCC.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Oren Shibolet, MD, Liver Unit, Department of Gastroenterology and Hepatology, Tel-Aviv Medical Center, 14 Weizman Street, Tel-Aviv 62431, Israel.
Telephone: +972-3-6973984 Fax: +972-3-6974622
Received: January 3, 2018
Peer-review started: January 4, 2018
First decision: January 16, 2018
Revised: March 10, 2018
Accepted: March 25, 2018
Article in press: March 25, 2018
Published online: April 21, 2018
Processing time: 105 Days and 13.1 Hours

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


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.


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).


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: Hepatocellular carcinoma, Aggressiveness index, Liver function, Transarterial chemoembolization, Survival

Core tip: Our cohort’s population included patients with multiple underlying liver diseases and can be widely generalized. The aggressiveness index (AgI) was correlated with survival. AgI > 4 was associated with decreased survival. Combining the AgI with elevated GGTP and ALKP levels improved its prognostic yield in our patient population. We validated the AgI as a prognostic tool to predict overall survival in a novel population of hepatocellular carcinoma patients undergoing transarterial chemoembolization.