Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication

作     者：Ayato Murata Takuya Genda Takafumi Ichida Nozomi Amano Sho Sato Hironori Tsuzura Shunsuke Sato Yutaka Narita Yoshio Kanemitsu Yuji Shimada Katsuharu Hirano Katsuyori Iijima Ryo Wada Akihito Nagahara Sumio Watanabe 

作者机构：Department of Gastroenterology and HepatologyJuntendo University Shizuoka Hospital Department of HepatologyShonan-East General Hospital Department of PathologyJuntendo University Shizuoka Hospital Department of GastroenterologyJuntendo University School of Medicine 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2016年第22卷第33期

页      面：7569-7578页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Supported by Grant-in-Aid from the Ministry of Health Labor and Welfare of Japan 

主　　题：Human AKR1B10 protein Hepatocellular carcinoma Chronic hepatitis C Immunohistochemistry Risk factor Sustained virological response 

摘      要：AIM To clarify the association between aldo-keto reductase family 1 member B10(AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.METHODS In this study,we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response(SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios(HRs) of AKR1B10 expression for hepatocellular carcinoma(HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test.RESULTS Of the 303 chronic hepatitis C patients,153(50.5%) showed scarce hepatic AKR1B10 expression,quantified as 0%,which was similar to the expression in control normal liver tissues. However,the remaining 150 patients(49.5%) exhibited various degrees of AKR1B10 expression in the liver,with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years(range 1.0-10.0 years),8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression(≥ 8%) was an independent risk factor for HCC development(HR = 15.4,95%CI: 1. 8- 1 3 2. 5,P = 0. 0 1 2). T h e 5- y e a r c u m u l a t i v e incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression,respectively(P 0.001). During the follow-up period after viral eradication,patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression.CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.