Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2019; 11(4): 322-334
Published online Apr 15, 2019. doi: 10.4251/wjgo.v11.i4.322
Validated model for prediction of recurrent hepatocellular carcinoma after liver transplantation in Asian population
Ka Wing Ma, Wong Hoi She, Albert Chi Yan Chan, Tan To Cheung, James Yan Yue Fung, Wing Chiu Dai, Chung Mau Lo, Kenneth Siu Ho Chok
Ka Wing Ma, Wong Hoi She, Wing Chiu Dai, Department of Surgery, the University of Hong Kong, Hong Kong, China
Albert Chi Yan Chan, Tan To Cheung, Chung Mau Lo, Kenneth Siu Ho Chok, Department of Surgery and State Key Laboratory for Liver Research, the University of Hong Kong, 102 Pokfulam Road, Hong Kong, China
James Yan Yue Fung, Department of Medicine and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
Author contributions: Ma KW was responsible for study design, data collection and analysis, manuscript writing, and proofreading; She WH, Chan ACY, Cheung TT, Fung JYY, Dai WC, and Lo CM were responsible for data collection and proofreading; Chok KSH was responsible for supervising the study, data collection, and proofreading.
Institutional review board statement: Institutional review board approval was not required for retrospective observational study.
Informed consent statement: Informed consent to the use of patient data for research purpose was obtained from all patients before transplantation.
Conflict-of-interest statement: None of the authors has any conflict of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Kenneth Siu Ho Chok, FRCS (Ed), Associate Professor, Department of Surgery, the University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China. chok6275@hku.hk
Telephone: +852-22553025
Received: November 19, 2018
Peer-review started: November 19, 2018
First decision: December 7, 2018
Revised: January 3, 2019
Accepted: January 8, 2019
Article in press: January 9, 2019
Published online: April 15, 2019
Processing time: 147 Days and 5.8 Hours
Abstract
BACKGROUND

Liver transplantation (LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma (HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive agents.

AIM

To develop a scoring system to predict HCC recurrence after LT in an Asian population.

METHODS

Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a 60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic curve.

RESULTS

In total, 330 patients were eligible for analysis (183 in training and 147 in validation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were 78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [P = 0.012, hazard ratio (HR) 2.92], sum of maximum tumor size and number (P = 0.013, HR 1.15), and salvage LT (P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power (c-stat 0.748 and 0.85, respectively, in the training and validation sets). With the derived scores, patients were classified into low- (0–9), moderate- (> 9–14), and high-risk groups (> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54% (c-stat 0.67) and 4%, 22%, 62% (c-stat 0.811), accordingly. The risk stratification model was validated with chi-squared goodness-of-fit test (P = 0.425).

CONCLUSION

A validated predictive model featuring alpha-fetoprotein, salvage LT, and the sum of largest tumor diameter and total number of tumor nodule provides simple and reliable guidance for individualizing postoperative surveillance strategy.

Keywords: Hepatocellular carcinoma; Liver transplantation; Post-transplant recurrence; Predictive model

Core tip: Recurrent hepatocellular carcinoma is the leading cause of death after liver transplantation. A validated predictive system for the chance of post-transplant recurrence of hepatocellular carcinoma is indispensable for stratifying patients into different risk groups. This study found that salvage liver transplantation, pre-transplant alpha-fetoprotein level, and the sum of pathological tumor size and number were the three independent factors associated with recurrence. Based on this, a scoring model was derived, validated, and found to have good concordance and is therefore recommendable to be used as a guide for postoperative patient surveillance.