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


CONCLUSIONS
Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Ayato
A
Murata
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Takuya
T
Genda
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Takafumi
T
Ichida
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Nozomi
N
Amano
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Sho
S
Sato
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Hironori
H
Tsuzura
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Shunsuke
S
Sato
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Yutaka
Y
Narita
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Yoshio
Y
Kanemitsu
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Yuji
Y
Shimada
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Katsuharu
K
Hirano
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Katsuyori
K
Iijima
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Ryo
R
Wada
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Akihito
A
Nagahara
Ayato Murata, Takuya Genda, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Shizuoka 410-2295, Japan.
Sumio
S
Watanabe
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000378:metabolism*; D000074408:Aldo-Keto Reductases; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000628:therapy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
Chronic hepatitis C; Hepatocellular carcinoma; Human AKR1B10 protein; Immunohistochemistry; Risk factor; Sustained virological response
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