Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 28, 2015; 7(27): 2757-2764
Published online Nov 28, 2015. doi: 10.4254/wjh.v7.i27.2757
Alpha-fetoprotein and des-gamma-carboxy-prothrombin at twenty-four weeks after interferon-based therapy predict hepatocellular carcinoma development
Satoshi Shakado, Shotaro Sakisaka, Kazuaki Chayama, Takeshi Okanoue, Joji Toyoda, Namiki Izumi, Akihiro Matsumoto, Tetsuo Takehara, Akio Ido, Yoichi Hiasa, Kentaro Yoshioka, Hideyuki Nomura, Yoshiyuki Ueno, Masataka Seike, Hiromitsu Kumada
Satoshi Shakado, Shotaro Sakisaka, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, Fukuoka City, Fukuoka 814-0180, Japan
Kazuaki Chayama, Department of Gastroenterology and Metabolism, Applied Life Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima City, Hiroshima 734-8553, Japan
Takeshi Okanoue, Center of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita City, Osaka 564-0013, Japan
Joji Toyoda, Department of Gastroenterology and Hepatology, Sapporo Kousei Hospital, Sapporo City, Hokkaido 060-0033, Japan
Namiki Izumi, Department of Gastroenterology and Hepatology, Musashino Red-Cross Hospital, Musashino City, Tokyo 180-8610, Japan
Akihiro Matsumoto, Department of Medicine, Shinshu University School of Medicine, Matsumoto City, Nagano 390-8621, Japan
Tetsuo Takehara, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita City, Osaka 565-0871, Japan
Akio Ido, Department of Gastroenterology and Hepatology, Kagoshima University, Kagoshima City, Kagoshima 890-8520, Japan
Yoichi Hiasa, Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime 791-0295, Japan
Kentaro Yoshioka, Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, Toyoake City, Aichi 470-1192, Japan
Hideyuki Nomura, the Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu City, Fukuoka 803-8505, Japan
Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University, Yamagata City, Yamagata 990-9585, Japan
Masataka Seike, Department of Gastroenterology, Faculty of Medicine, Oita University, Yufu City, Oita 879-5593, Japan
Hiromitsu Kumada, Department of Hepatology, Toranomon Hospital, Kawasaki City, Kanagawa 213-8587, Japan
Author contributions: Shakado S and Sakisaka S performed the study design, acquisition, analysis and interpretation of data, literature search, drafting of the manuscript; Chayama K, Okanoue T, Toyoda J, Izumi N, Matsumoto A, Takehara T, Ido A, Hiasa Y, Yoshioka K, Nomura H, Ueno Y, Seike M and Kumada H contributed to the acquisition of data.
Supported by A Grant-in-Aid from the Japanese Ministry of Health, Welfare and Labour.
Institutional review board statement: The study was not needed to approve by the institutional review board.
Informed consent statement: This study is a retrospective report. The additional informed consent from the patients does not apply.
Conflict-of-interest statement: Shotaro Sakisaka received Research Fund from MSD; Kazuaki Chayama received Research Fund from AbbVie, Dainippon Sumitomo, Janssen, Daiichi Sankyo, Roche, MSD, Toray, Otsuka and Tanabe; and Kazuaki Chayama received lecture fees form MSD and Bristol-Myers; Namiki Izumi received lecture fees from Chugai, MSD, Bristol-Myers, Dainippon Sumitomo, Janssen; Tetsuo Takehara received Research Fund from MSD; and Tetsuo Takehara received lecture fees form MSD; Akio Ido received Research Fund from Chugai, MSD, Dai-ichi Sankyo and Tanabe; Kentaro Yoshioka received Research Fund from MSD; and Kentaro Yoshioka had an advisory role to Sanwa Kagaku Kenkyusho; Yoshiyuki Ueno received Research Fund from Tanabe, MSD, Chugai, BMS and Gilead Sciences; Hiromitsu Kumada received lecture fees from MSD K.K, Bristol-Myers Squibb, Janssn Pharmaceutical K.K, Glaxo Smith Kline K.K; and Hiromitsu Kumada had patentroyalties from SRL.
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: Satoshi Shakado, MD, Associate Professor, Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka City, Fukuoka 814-0180, Japan. shakado@cis.fukuoka-u.ac.jp
Telephone: +81-92-8011011 Fax: +81-92-8742663
Received: May 30, 2015
Peer-review started: June 1, 2015
First decision: July 6, 2015
Revised: August 27, 2015
Accepted: November 13, 2015
Article in press: November 17, 2015
Published online: November 28, 2015
Processing time: 181 Days and 1.6 Hours
Abstract

AIM: To investigate risk factors for development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus-related liver cirrhosis (LC-C).

METHODS: To evaluate the relationship between clinical factors including virological response and the development of HCC in patients with LC-C treated with interferon (IFN) and ribavirin, we conducted a multicenter, retrospective study in 14 hospitals in Japan. All patients had compensated LC-C with clinical or histological data available. HCC was diagnosed by the presence of typical hypervascular characteristics on computed tomography and/or magnetic resonance imaging.

RESULTS: HCC was diagnosis in 50 (21.6%) of 231 LC-C patients during a median observation period of 3.8 years after IFN and ribavirin therapy. Patients who developed HCC were older (P = 0.018) and had higher serum levels of pretreatment alpha-fetoprotein (AFP) (P = 0.038). Multivariate analysis revealed the following independent risk factors for HCC development: history of treatment for HCC [P < 0.001, odds ratio (OR) = 15.27, 95%CI: 4.98-59.51], AFP levels of ≥ 10 ng/mL (P = 0.009, OR = 3.89, 95%CI: 1.38-11.94), and des-γ-carboxy prothrombin (DCP) levels of ≥ 40 mAU/mL at 24 wk after the completion of IFN and ribavirin therapy (P < 0.001, OR = 24.43, 95%CI: 4.11-238.67).

CONCLUSION: We suggested that the elevation of AFP and DCP levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.

Keywords: Des-γ-carboxy prothrombin; Hepatocellular carcinoma; Alpha-fetoprotein; Interferon; Hepatitis C virus; Liver cirrhosis; Ribavirin

Core tip: Interferon (IFN)-based therapy reduces the rate of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) infection. However, HCC development has frequently been reported in HCV-related liver cirrhosis (LC-C) patients who achieved sustained virological response. We conducted a multicenter, retrospective study to evaluate the relationship between clinical factors and HCC development in Japanese LC-C patients treated with IFN and ribavirin therapy. We suggested that the elevation of Alpha-fetoprotein and des-γ-carboxy prothrombin levels at 24 wk after the completion of IFN and ribavirin therapy were strongly associated with the incidence of HCC irrespective of virological response among Japanese LC-C patients.