Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2015; 21(29): 8935-8942
Published online Aug 7, 2015. doi: 10.3748/wjg.v21.i29.8935
Interferon-λ polymorphisms and response to pegylated interferon in Iranian hepatitis C patients
Arghavan Haj-sheykholeslami, Maryam Keshvari, Heidar Sharafi, Ali Pouryasin, Khalil Hemmati, Fatemeh Mohammadzadehparjikolaei
Arghavan Haj-sheykholeslami, Khalil Hemmati, Fatemeh Mohammadzadehparjikolaei, The Liver, Pancreatic, and Biliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
Maryam Keshvari, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran 14665-1157, Iran
Heidar Sharafi, Middle East Liver Disease Center, Tehran 14155-3651, Iran
Heidar Sharafi, Ali Pouryasin, Armin Pathobiology Laboratory, Tehran 1235642351, Iran
Author contributions: Keshvari M and Pouryasin A designed the research; All patients were evaluated and treated by Keshvari M; Sharafi H and Pouryasin A performed the molecular assessments; Hemmati K and Mohammadzadehparjikolaei F extracted the data from the patients’ documents and completed the side effect questionnaires by interviewing the patients; Sharafi H performed the statistical analysis; and Haj-sheykholeslami A wrote the article and the final draft was reviewed by Keshvari M.
Supported by Pooyesh Darou which is the local manufacturer of pegylated interferon alpha-2a in Iran (Pegaferon).
Institutional review board statement: This study was approved by the Ethics Committee of the Iranian Blood Transfusion Organization. The study protocol conformed to the ethical guidelines of the 1975 declaration of Helsinki.
Informed consent statement: Informed consent was obtained from all patients participating in the study.
Conflict-of-interest statement: This study was financially supported by Pooyesh Darou, which is the local manufacturer of pegylated interferon alpha-2a in Iran (Pegaferon®). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Data sharing statement: Dataset is available from the corresponding author at
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:
Correspondence to: Maryam Keshvari, MD, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran 14665-1157, Iran.
Telephone: +98-21-66592126 Fax: +98-21-66900386
Received: November 23, 2014
Peer-review started: November 24, 2014
First decision: December 11, 2014
Revised: February 10, 2015
Accepted: April 9, 2015
Article in press: April 9, 2015
Published online: August 7, 2015

AIM: To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-λ (IFNL) polymorphisms.

METHODS: This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type of pegylated interferon. Patients were treated with 180 μg pegylated interferon alpha-2a (Pegaferon®) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus (HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes.

RESULTS: A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men (92.8%). The most frequent HCV genotype was type-1, infecting 93/152 (61.2%) patients. Sustained virologic response (SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2% (52/57) of patients with the IFNL rs12979860 CC genotype and 82.1% (78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT (39/45; 86.7%) and non-TT (61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR (OR = 6.2; 95%CI: 1.2-31.9; P = 0.03).

CONCLUSION: The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.

Keywords: Chronic hepatitis C, Pegylated interferon, rs12979860, rs8099917, Sustained virologic response

Core tip: Chronic hepatitis C-infected Iranian patients treated with pegylated interferon and ribavirin showed relatively high rates of sustained virologic response. Treatment success was not influenced by hepatitis C virus genotype. However, a comparison of treatment success related to IFNL polymorphisms (also known as IL28B polymorphisms) using a logistic regression analysis revealed that the interferon-λ rs12979860 CC genotype was significantly associated with achieving a sustained virologic response.