title: The relationship between IL-28B polymorphisms and the response to peginterferon alfa-2a monotherapy in anti-HBe-positive patients with chronic HBV infection.
abstract: The impact of interleukin 28B (IL-28B) on the results of interferon (IFN)-based therapy in patients chronically infected with hepatitis B virus (HBV) is poorly understood. The aim of this study was to evaluate the relationship between IL-28B markers and the response to IFN monotherapy in Polish patients with anti-hepatitis B e (HBe)-positive chronic hepatitis B (CHB). We determined three single-nucleotide polymorphisms (SNPs) of IL-28B (rs12979860, rs12980275, and rs8099917) in 86 patients who were treated with pegylated interferon (PEG-IFN) for 48 weeks. The effectiveness of the therapy was evaluated based on the virological and biochemical response. The primary efficacy parameters were the HBV DNA viral load below 400 IU/ml and 2,000 IU/ml in combination with alanine aminotransferase (ALT) normalization (<40 IU/l), measured 24 weeks after the treatment. Viral load below 400 IU/ml or 2,000 IU/ml with ALT normalization was achieved by 37 % and 46 % of patients, respectively. It has been shown that the distribution of IL-28B genotypes in the dominant genetic model in patients with different therapeutic success differ significantly only for rs12979860. The IL-28B rs12979860 CC genotype was associated with lower treatment success [odds ratio (OR), 0.31; p = 0.025 and OR, 0.37; p = 0.044 for <400 IU/ml HBV DNA with <40 IU/l ALT, and <2,000 IU/ml HBV DNA with <40 IU/l ALT, respectively]. However, in the conditional logistic regression analysis adjusted by factors associated with combined response, rs12979860 was significantly associated only with <400 IU/ml HBV DNA with <40 IU/l ALT (OR, 0.24; p = 0.026). IL-28B polymorphisms have prognostic significance in assessing the treatment effectiveness based on the virological and biochemical response of patients with anti-HBe-positive CHB.
authors.affiliation: Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Domagalski
authors.forename: M
authors.initials: M
authors.lastname: Pawłowska
authors.forename: A
authors.initials: A
authors.lastname: Zaleśna
authors.forename: M
authors.initials: M
authors.lastname: Tyczyno
authors.forename: M
authors.initials: M
authors.lastname: Skorupa-Kłaput
authors.forename: A
authors.initials: A
authors.lastname: Tretyn
authors.forename: W
authors.initials: W
authors.lastname: Halota
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a