1. Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication
- Author
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Ryo Wada, Nozomi Amano, Hironori Tsuzura, Takafumi Ichida, Katsuyori Iijima, Katsuharu Hirano, Akihito Nagahara, Sumio Watanabe, Yutaka Narita, Sho Sato, Ayato Murata, Yuji Shimada, Yoshio Kanemitsu, Takuya Genda, and Shunsuke Sato
- Subjects
Male ,Hepatocellular carcinoma ,viruses ,Hepacivirus ,Treatment outcome ,Aldo-Keto Reductases ,medicine.disease_cause ,Chronic hepatitis C ,0302 clinical medicine ,Risk Factors ,Medicine ,Aged, 80 and over ,biology ,Liver Neoplasms ,Gastroenterology ,General Medicine ,Hepatitis C ,Middle Aged ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Sustained virological response ,Treatment Outcome ,030220 oncology & carcinogenesis ,Human AKR1B10 protein ,030211 gastroenterology & hepatology ,Female ,Adult ,Carcinoma, Hepatocellular ,Genotype ,Hepatitis C virus ,macromolecular substances ,03 medical and health sciences ,Young Adult ,Retrospective Study ,Aldehyde Reductase ,Carcinoma ,Humans ,Risk factor ,Aged ,Retrospective Studies ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,biology.organism_classification ,digestive system diseases ,Cancer research ,business - Abstract
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: 1.8-132.5, P = 0.012). The 5-year cumulative 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.
- Published
- 2016