Interferon-λ polymorphisms and response to pegylated interferon in Iranian hepatitis C patients

World J Gastroenterol. 2015 Aug 7;21(29):8935-42. doi: 10.3748/wjg.v21.i29.8935.

Abstract

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; Sustained virologic response; rs12979860; rs8099917.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Iran
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Pharmacogenetics
  • Phenotype
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • RNA, Viral / blood
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • IFNL3 protein, human
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a