Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Sep 8, 2015; 7(19): 2220-2228
Published online Sep 8, 2015. doi: 10.4254/wjh.v7.i19.2220
Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development
Yasuto Takeuchi, Fusao Ikeda, Toshiya Osawa, Yasuyuki Araki, Kouichi Takaguchi, Youichi Morimoto, Noriaki Hashimoto, Kousaku Sakaguchi, Tatsuro Sakata, Masaharu Ando, Yasuhiro Makino, Shuji Matsumura, Hiroki Takayama, Hiroyuki Seki, Shintarou Nanba, Yuki Moritou, Tetsuya Yasunaka, Hideki Ohnishi, Akinobu Takaki, Kazuhiro Nouso, Yoshiaki Iwasaki, Kazuhide Yamamoto
Yasuto Takeuchi, Fusao Ikeda, Hiroyuki Seki, Shintarou Nanba, Yuki Moritou, Tetsuya Yasunaka, Hideki Ohnishi, Akinobu Takaki, Kazuhiro Nouso, Kazuhide Yamamoto, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
Fusao Ikeda, Hideki Ohnishi, Kazuhiro Nouso, Kazuhide Yamamoto, Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-0914, Japan
Toshiya Osawa, Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700-0013, Japan
Yasuyuki Araki, Department of Internal Medicine, Hiroshima City Hospital, Hiroshima 730-8518, Japan
Kouichi Takaguchi, Department of Internal Medicine, Kagawa Prefectural Central Hospital, Takamatsu 760-0065, Japan
Youichi Morimoto, Department of Internal Medicine, Kurashiki Central Hospital, Kurashiki 710-0052, Japan
Noriaki Hashimoto, Department of Internal Medicine, Mihara Red Cross hospital, Mihara 723-0011, Japan
Kousaku Sakaguchi, Department of Internal Medicine, Fukuyama City Hospital, Fukuyama 721-0971, Japan
Tatsuro Sakata, Department of Internal Medicine, National Hospital Organization Fukuyama Clinical Center, Fukuyama 720-0825, Japan
Masaharu Ando, Department of Internal Medicine, Mitoyo General Hospital, Kanonji 769-1601, Japan
Yasuhiro Makino, Department of Gastroenterology, National Hospital Organization Iwakuni Clinical Center, Iwakuni 740-0041, Japan
Shuji Matsumura, Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama 792-8543, Japan
Hiroki Takayama, Department of Gastroenterology, Tsuyama Central Hospital, Okayama 708-0841, Japan
Yoshiaki Iwasaki, Health Service Center, Okayama University, Okayama 700-0914, Japan
Author contributions: All authors contributed to this manuscript.
Supported by In part a Research Program for Intractable Disease by the Ministry of Health, Labor, and Welfare of Japan (to Iwasaki Y).
Institutional review board statement: All protocols were approved by the ethics committees of the institutes.
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: No conflict-of-interest exists for the article.
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: Fusao Ikeda, MD, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. fikeda@md.okayama-u.ac.jp
Telephone: +81-86-2357219 Fax: +81-86-2255991
Received: March 18, 2015
Peer-review started: March 22, 2015
First decision: April 27, 2015
Revised: June 20, 2015
Accepted: June 30, 2015
Article in press: July 2, 2015
Published online: September 8, 2015
Processing time: 174 Days and 18.6 Hours
Abstract

AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients.

METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy.

RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/mL before therapy and in non-SVR patients showing AFP ≥ 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP ≥ 5 ng/mL.

CONCLUSION: The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

Keywords: Hepatitis C virus; Interferon; Hepatocellular carcinoma; Alpha-fetoprotein

Core tip: What is current knowledge: (1) Alpha-fetoprotein (AFP) values can predict development of hepatocellular carcinoma (HCC) after interferon therapy in patients with hepatitis C virus; and (2) The predictive value of AFP on HCC development after interferon therapy and its criteria remained uncertain. What is new here: AFP values before interferon therapy have strong predictive value on HCC development after interferon therapy. The simple criteria defined by AFP values before and 1 year after interferon therapy might work efficient to predict HCC development after interferon therapy.