Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5607-5621
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5607
Significance of platelet count and platelet-based models for hepatocellular carcinoma recurrence
Qing Pang, Jing-Yao Zhang, Xin-Sen Xu, Si-Dong Song, Kai Qu, Wei Chen, Yan-Yan Zhou, Run-Chen Miao, Su-Shun Liu, Ya-Feng Dong, Chang Liu
Qing Pang, Jing-Yao Zhang, Xin-Sen Xu, Si-Dong Song, Kai Qu, Wei Chen, Yan-Yan Zhou, Run-Chen Miao, Su-Shun Liu, Chang Liu, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Ya-Feng Dong, Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Lawrence, KS 66045, United States
Author contributions: Pang Q, Zhang JY and Xu XS contributed equally to this work; Pang Q, Dong YF and Liu C designed the research; Xu XS, Chen W, Zhou YY and Miao RC collected the data; Xu XS, Song SD and Qu K sorted the data; Chen W, Zhou YY and Miao RC performed the follow-ups; Zhang JY and Xu XS analyzed the data; Pang Q and Zhang JY wrote the paper; Xu XS, Song SD, Qu K and Liu SS revised the paper.
Supported by National Natural Science Foundation of China, No. 30872482 and No. 81072051.
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: Chang Liu, MD, PhD, Professor, Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, No. 277 West Yan-ta Road, Xi’an 710061, Shaanxi Province, China.
Telephone: +86-29-82653900 Fax: +86-29-82653905
Received: July 30, 2014
Peer-review started: July 30, 2014
First decision: August 15, 2014
Revised: September 2, 2014
Accepted: October 15, 2014
Article in press: October 15, 2014
Published online: May 14, 2015

AIM: To explore the effects of platelet count (PLT) and 11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma (HCC).

METHODS: We retrospectively analyzed 172 HCC patients who were treated by partial hepatectomy. Preoperative data, including laboratory biochemical results, were used to calculate the 11 indices included in the analysis. We performed receiver operating characteristic curve analysis to determine the optimal cut-off values for predicting recurrence. Cumulative rates of HCC recurrence were calculated using Kaplan-Meier survival curves and differences were analyzed by log-rank tests. Multivariate analyses were performed to identify independent predictors of recurrence, early recurrence (within one year after surgery), and late recurrence in HCC. To obtain better prognostic models, PLT-based indices were analyzed separately after being expressed as binary and continuous variables. Two platelet-unrelated, validated HCC prognostic models were included in the analyses as reference indices. Additional analyses were performed after patients were stratified based on hepatitis B virus infection status, cirrhosis, and tumor size to investigate the significance of platelets in different subgroups.

RESULTS: In the study cohort, 44.2% (76/172) of patients experienced HCC recurrence, and 50.6% (87/172) died during a median follow-up time of 46 mo. PLT and five of the 11 platelet-related models were significant predisposing factors for recurrence (P < 0.05). Multivariate analysis indicated that, among the clinical parameters, presence of ascites, PLT ≥ 148 × 109/L, alkaline phosphatase ≥ 116 U/L, and tumor size ≥ 5 cm were independently associated with a higher risk of HCC recurrence (P < 0.05). Independent and significant models included the aspartate aminotransferase/PLT index, fibrosis index based on the four factors, fibro-quotient, aspartate aminotransferase/PLT/γ-glutamyl transpeptidase/alpha-fetoprotein index, and the PLT/age/alkaline phosphatase/alpha-fetoprotein/aspartate aminotransferase index. There were different risk factors between early and late recurrences, and PLT and these indices were more inclined to influence late recurrence. PLT was only predictive of recurrence in non-cirrhotic HCC patients, and was not influenced by tumor size, which was a critical confounder in our study.

CONCLUSION: PLT and PLT-based noninvasive models are effective tools for predicting postoperative recurrence, especially late recurrence. Larger cohorts are needed to validate our findings.

Keywords: Alkaline phosphatase, Alpha-fetoprotein, Aspartate aminotransferase, Blood platelets, Hepatocellular carcinoma, Recurrence

Core tip: The high risk of postoperative recurrence is one of the greatest problems plaguing potential curative treatment for hepatocellular carcinoma (HCC). Although several prognostic models have been proposed for HCC, these indices mainly focus on non-modifiable tumor characteristics. In contrast, platelet count is an improvable variable, and there are numerous platelet-based models associated with cirrhosis and HCC formation. We found that platelet count and nearly half of the established platelet-related models were independently associated with postoperative recurrence. We also demonstrated different risk factors between early and late recurrences, with platelets more likely to influence late recurrence.