Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2017; 23(44): 7863-7874
Published online Nov 28, 2017. doi: 10.3748/wjg.v23.i44.7863
Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis
Ka-Shing Cheung, Wai-Kay Seto, James Fung, Lung-Yi Mak, Ching-Lung Lai, Man-Fung Yuen
Ka-Shing Cheung, Wai-Kay Seto, James Fung, Lung-Yi Mak, Ching-Lung Lai, Man-Fung Yuen, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
Wai-Kay Seto, James Fung, Ching-Lung Lai, Man-Fung Yuen, State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
Author contributions: Cheung KS designed and performed the study, were involved in statistical analysis and interpretation of the data, and wrote the manuscript; Seto WK and Mak LY performed the study, statistical analysis and interpretation of the data; Fung J, Lai CL and Yuen MF revised and edited the manuscript.
Institutional review board statement: This study was approved by The Institutional Review Board of The University of Hong Kong/Hospital Authority, Hong Kong West Cluster.
Informed consent statement: The Institutional Review Board of The University of Hong Kong/Hospital Authority waived the need for written informed consent as there was no direct contact with eligible subjects and no additional blood taking.
Conflict-of-interest statement: The authors have no conflicts of interest.
Data sharing statement: No additional data are available.
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/
Correspondence to: Man-Fung Yuen, Professor, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China. mfyuen@hkucc.hku.hk
Telephone: +852-22553984 Fax: +852-28162863
Received: July 28, 2017
Peer-review started: July 28, 2017
First decision: August 30, 2017
Revised: September 25, 2017
Accepted: September 28, 2017
Article in press: September 28, 2017
Published online: November 28, 2017
Processing time: 122 Days and 21.6 Hours
ARTICLE HIGHLIGHTS
Research background

No reliable predictive models exist for hepatocellular carcinoma (HCC) in primary biliary cholangitis (PBC). Aspartate aminotransferase (AST) to platelet ratio index (APRI) not only captures fibrosis/cirrhosis, but also reflects other biologically significant pathways like hepatic necroinflammation or non-cirrhotic portal hypertension. The usefulness of APRI in predicting HCC in PBC remains unknown.

Research motivation

A predictive marker for HCC development in PBC patients will help disease prognostication and streamline the follow-up and HCC surveillance strategy.

Research objectives

To investigate the usefulness of APRI in predicting HCC in PBC.

Research methods

The authors recruited all PBC patients who had follow-up in the Hepatology Clinic of Queen Mary Hospital (QMH) between January 2000 and October 2015. Patients were followed up every 3 to 6 mo with regular monitoring of platelet count, liver biochemistry, prothrombin time and alpha-fetoprotein level. In the analysis of the risk factors for adverse events, suboptimal response to UDCA was identified by using various treatment response criteria. APRI-r1 in combination with treatment response criteria enables further stratification of PBC patients into low-risk (biochemical response with APRI-r1 ≤ 0.54), intermediate-risk (suboptimal biochemical response with APRI-r1 ≤ 0.54, or biochemical response with APRI-r1 > 0.54) and high-risk (suboptimal biochemical response with APRI-r1 > 0.54) groups of developing adverse outcomes in terms of liver transplantation or death. The Cox proportional hazards model was used to determine the hazard ratio (HR) of HCC with different variables. The Kaplan-Meier method was used to analyze the development of HCC. The performances of various prognostic models were expressed in terms of area under the receiver operating curve (AUROC).

Research results

A total of 144 patients were identified. The median age at diagnosis was 57.8 years (interquartile range: 48.7-71.5 years), and 41 (28.5%) had baseline cirrhosis. The median follow-up duration was 6.9 years (range: 1.0-26.3 years), with a total of 1136 patient-years. Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10- and 15-year probabilities of HCC development were 2.3% [95% confidence interval (CI): 0%-4.8%], 8.4% (95%CI: 1.8%-14.5%) and 21.6% (6.8%-34.1%), respectively. Independent risk factors for HCC development were older age (HR = 1.07), cirrhosis (HR = 4.38) and APRI at 1 year after treatment (APRI-r1) > 0.54 (HR = 3.94). APRI-r1 in combination with treatment response further stratified the risk of HCC development (log rank P < 0.05). The AUROC of APRI-r1 in predicting HCC was 0.77 (95%CI: 0.64-0.88).

Research conclusions

APRI-r1 can be used as a predictive marker for HCC development in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

Research perspectives

Our study confirmed the usefulness of APRI-r1 in predicting HCC development in PBC patients receiving UDCA. The combination of APRI-r1 with treatment response allowed further stratification of HCC risk. Owing to its non-invasiveness and cost-effectiveness, APRI can be used as a marker to streamline the HCC surveillance protocol in PBC patients. Future multi-center studies with larger sample size are warranted to confirm our findings.