Published online Sep 7, 2016. doi: 10.3748/wjg.v22.i33.7569
Peer-review started: May 23, 2016
First decision: June 20, 2016
Revised: July 4, 2016
Accepted: August 1, 2016
Article in press: August 1, 2016
Published online: September 7, 2016
To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.
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.
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.
Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.
Core tip: Expression of a cancer-related oxidoreductase, aldo-keto reductase family 1 member B10 (AKR1B10) was upregulated in the liver in patients with chronic hepatitis C (CHC). High AKR1B10 expression was associated in a statistically significant manner with the risk of hepatocellular carcinoma (HCC) development even after sustained virological response (SVR) was achieved through interferon-based antiviral therapy. Pretreatment AKR1B10 expression of 8% was associated with a > 15-fold-increased risk of HCC development. Thus, AKR1B10 is not only a cancer biomarker but also a novel predictive marker for assessing the risk of HCC development in CHC patients who achieved SVR.