Viral Hepatitis
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 21, 2006; 12(23): 3722-3728
Published online Jun 21, 2006. doi: 10.3748/wjg.v12.i23.3722
Mutations in carboxy-terminal part of E2 including PKR/eIF2α phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: Their correlation with response to interferon monotherapy and viral load
Koji Ukai, Masatoshi Ishigami, Kentaro Yoshioka, Naoto Kawabe, Yoshiaki Katano, Kazuhiko Hayashi, Takashi Honda, Motoyoshi Yano, Hidemi Goto
Koji Ukai, Masatoshi Ishigami, Yoshiaki Katano, Kazuhiko Hayashi, Takashi Honda, Motoyoshi Yano, Hidemi Goto, Division of Gastroenterology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Kentaro Yoshioka, Naoto Kawabe, Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University School of Medicine, Aichi, Japan
Correspondence to: Kentaro Yoshioka, MD, Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan. kyoshiok@fujita-hu.ac.jp
Telephone: +81-562-939240 Fax: +81-562-938300
Received: January 25, 2006
Revised: January 28, 2006
Accepted: February 28, 2006
Published online: June 21, 2006
Abstract

AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-1b-infected patients treated with IFN.

METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2α phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy.

RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9%, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response.

CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.

Keywords: E2, Genotype, HCV, Interferon, ISDR, NS5A, PePHD, PKR, SVR