Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2015; 21(13): 3904-3911
Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3904
Interferon-λ3 polymorphisms in pegylated-interferon-α plus ribavirin therapy for genotype-2 chronic hepatitis C
Haruya Ishiguro, Hiroshi Abe, Nobuyoshi Seki, Tomonori Sugita, Yuta Aida, Munenori Itagaki, Satoshi Sutoh, Noritomo Shimada, Tomomi Furihata, Akihito Tsubota, Yoshio Aizawa
Haruya Ishiguro, Hiroshi Abe, Nobuyoshi Seki, Tomonori Sugita, Yuta Aida, Munenori Itagaki, Satoshi Sutoh, Yoshio Aizawa, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, Tokyo 125-8506, Japan
Noritomo Shimada, Department of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba 270-0034, Japan
Tomomi Furihata, Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan
Akihito Tsubota, Core Research Facilities for Basic Science, Research Center for Medical Science, Jikei University School of Medicine, Tokyo 105-8461, Japan
Author contributions: Ishiguro H, Abe H, Sutoh S and Aizawa Y designed the research; Furihata T and Tsubota A examined the IFNL3 polymorphism; Ishiguro H, Abe H, Seki N, Sugita T, Aida Y, Itagaki M and Shimada N analyzed the data; Ishiguro H, Abe H, Tsubota A and Aizawa Y wrote the paper.
Ethics approval: The study was reviewed and approved by the Jikei University School of Medicine Institutional Review Board.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: All authors declare no conflicts of interest.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Haruya Ishiguro, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan. haruya713@yahoo.co.jp
Telephone: +81-3-36032111 Fax: +81-3-38389944
Received: September 16, 2014
Peer-review started: September 19, 2014
First decision: November 5, 2014
Revised: November 29, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 7, 2015
Abstract

AIM: To evaluate interferon-λ3 (IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin (Peg-IFNα/RBV) therapy for genotype 2 (G2) chronic hepatitis C.

METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were treated with response-guided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV sub-genotype 2a or 2b.

RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.

CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.

Keywords: Hepatitis C virus genotype 2, Interferon-λ3 single nucleotide polymorphism, Pegylated-interferon plus ribavirin response-guided therapy, Rapid virologic response, Sustained virologic response

Core tip: Interferon-λ3 (IFNL3) single nucleotide polymorphisms (SNPs), such as rs8099917 and rs12979860, affect the virologic responses of chronically hepatitis C virus genotype 1-infected patients to response-guided pegylated interferon-α plus ribavirin therapy. However, the significance of these SNPs in therapy for hepatitis C virus genotype 2 (G2)-infected patients is unclear. We show that rs8099917 significantly influences sustained virologic response (SVR) achievement only in patients who do not attain rapid virologic response. Therefore, IFNL3 SNP genotyping is valuable for predicting SVR only in non-rapid virologic response patients, irrespective of the G2 subtype, even when therapy is extended up to 48 wk.