title: Impact of aldo-keto reductase family 1 member B10 on the risk of hepatitis C virus-related hepatocellular carcinoma.
abstract: OBJECTIVE
  Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection.
  
  
  METHODS
  Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method.
  
  
  RESULTS
  Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P < 0.001). The 5-year cumulative incidences of HCC were 22.8% and 2.2% in patients with high and low AKR1B10 expression, respectively (P < 0.001). In subgroup analyses, the effects of high AKR1B10 expression on HCC development risk were significant over strata. In particular, HRs attributed to high AKR1B10 expression were significant in the subgroups that had been considered at a lower risk of HCC, such as in patients with younger age and mild hepatic fibrosis or those who achieved sustained virological response after interferon therapy.
  
  
  CONCLUSIONS
  Various degrees of AKR1B10 upregulation in the liver were observed in patients with chronic HCV infection, and high AKR1B10 expression could be a novel predictor of HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Genda
authors.affiliation: Department of Hepatology, East Shonan General Hospital, Kanagawa, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Ayato
authors.initials: A
authors.lastname: Murata
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsuzura
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Narita
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kanemitsu
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Internal Medicine, Fujinomiya City General Hospital, Fujinomiya, Shizuoka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Hepatology, East Shonan General Hospital, Kanagawa, Japan.
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Hirano
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Katsuyori
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pathology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Wada
authors.affiliation: Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nagahara
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000235:genetics* / Q000378:metabolism*; D000074408:Aldo-Keto Reductases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015870:Gene Expression; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012306:Risk; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
keywords: AKR1B10; chronic hepatitis C; hepatocellular carcinoma