Amino acid substitutions in the hepatitis C virus core region are the important predictor of hepatocarcinogenesis

✍ Scribed by Norio Akuta; Fumitaka Suzuki; Yusuke Kawamura; Hiromi Yatsuji; Hitomi Sezaki; Yoshiyuki Suzuki; Tetsuya Hosaka; Masahiro Kobayashi; Mariko Kobayashi; Yasuji Arase; Kenji Ikeda; Hiromitsu Kumada

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 161 KB
• Volume: 46
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.21836

✦ Synopsis

We showed previously that amino acid (aa) substitutions in hepatitis C virus core region (HCV-CR) are negative predictors of virologic response to pegylated interferon (IFN) plus ribavirin therapy. HCV-CR induces hepatocellular carcinoma in transgenic mice, but the clinical impact is still unclear. To evaluate the impact of aa substitutions in HCV-CR on hepatocarcinogenesis, we performed a follow-up study on 313 noncirrhotic consecutive naïve patients infected with HCV genotype 1b who received IFN monotherapy. The median follow-up was 14.7 years. A sustained virologic response (SVR) after the first IFN was achieved by 65 patients (20.8%) (group A). Of 248 patients (79.2%) of non-SVR after first IFN, 112 (35.8%) did not receive additional IFN (group B), and the remaining 136 (43.5%) received multicourse IFN monotherapy (group C). As a whole, cumulative hepatocarcinogenesis rates in double wild-type (arginine at aa 70/leucine at aa 91) of HCV-CR were significantly lower than those in nondouble wild-type. Multivariate analyses identified 3 parameters (fibrosis stage 3, nondouble wild-type of HCV-CR, and group B) that tended to or significantly influenced hepatocarcinogenesis independently. With regard to hepatocarcinogenesis rates in group C according to HCV-CR and the mean alanine aminotransferase (ALT) during IFN-free period, significantly higher rates were noted in patients of nondouble wild-type with ALT levels of more than 1.5 times the upper limit of normal (25.7%) compared with the others (2.4%).

Conclusion:

Amino acid substitutions in the hcv-cr are the important predictor of hepatocarcinogenesis. in multicourse ifn therapy to nondouble wild-type, we emphasize the importance of reducing the risk of hepatocarcinogenesis by mean alt during an ifn-free period below 1.5 times the upper limit of normal.