Brief Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Hepatol. Nov 27, 2013; 5(11): 635-641
Published online Nov 27, 2013. doi: 10.4254/wjh.v5.i11.635
IL-28B polymorphisms and treatment response in hepatitis C virus patients with persistently normal alanine aminotransferase
Tatsuo Miyamura, Tatsuo Kanda, Masato Nakamura, Xia Jiang, Shuang Wu, Shingo Nakamoto, Shigeru Mikami, Nobuo Takada, Fumio Imazeki, Osamu Yokosuka
Tatsuo Miyamura, Tatsuo Kanda, Masato Nakamura, Xia Jiang, Shuang Wu, Shingo Nakamoto, Osamu Yokosuka, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8677, Japan
Shigeru Mikami, Department of Internal Medicine, Kikkoman General Hospital, Noda 278-0005, Japan
Nobuo Takada, Department of Internal Medicine, Toho University, Sakura Medical Centre, Sakura 285-8741, Japan
Fumio Imazeki, Safety and Health Organization, Chiba University, Chiba 263-8522, Japan
Author contributions: Miyamura T and Kanda T designed the study and performed the majority of experiments; Kanda T, Mikami S, Takada N, Imazeki F and Yokosuka O collected all human samples; Miyamura T, Kanda T, Nakamura M, Jiang X and Wu S analyzed the data; Kanda T drafted the manuscript; all authors approved the manuscript.
Supported by Grants for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; and Grants from the Ministry of Health, Labour and Welfare of Japan
Correspondence to: Tatsuo Kanda, MD, PhD, Associate Professor, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan. kandat-cib@umin.ac.jp
Telephone: +81-43-2262086 Fax: +81-43-2262088
Received: September 1, 2013
Revised: October 7, 2013
Accepted: November 2, 2013
Published online: November 27, 2013
Processing time: 86 Days and 22 Hours
Abstract

AIM: To examine the association between the interleukin 28B (IL-28B) genotype and treatment response in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT).

METHODS: We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT. Between February 2010 and April 2013, 278 patients infected with HCV were enrolled in this study. All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin. In addition, 180 μg of peginterferon alpha-2a or 1.5 μg/kg peginterferon alpha-2b per week plus weight-based ribavirin (600-1000 mg/d) were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients. In all of the patients, the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay. HCV RNA was measured using the COBAS TaqMan HCV test.

RESULTS: Female patients were dominant in the PNALT group (P < 0.0001). Among 72 HCV genotype 1-infected patients with PNALT, the early virologic response (EVR) rates (P < 0.01) and the sustained virologic response (SVR) rates (P < 0.01) were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype. In HCV genotype 1-infected patients with PNALT, multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type (P < 0.05) and having an EVR (P < 0.01). The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT.

CONCLUSION: The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

Keywords: Hepatitis C virus; Interleukin 28B; Persistent normal alanine aminotransferase levels; Standard of care; Treatment response

Core tip: Whether the interleukin 28B (IL-28B) genotype affects the treatment response to peginterferon plus ribavirin in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT) is unclear. We examined the association between the IL-28B genotype and treatment response in HCV-infected patients with PNALT. Opinions about the appropriate treatment method for HCV-infected patients with PNALT differ. In the present study, we found that IL-28B rs8099917 TT was associated with SVR in HCV genotype 1-infected Asian patients with PNALT. The determination of IL-28B genotype is important for the successful treatment of HCV genotype 1-infected patients with PNALT.