title: Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotypes 2a and 2b and high viral load.
abstract: OBJECTIVE
  We investigated the impact of host genetics represented by the single nucleotide polymorphism (SNP) of the IL28B gene and viral genetic variations within the nonstructural protein 5A (NS5A) [including the interferon (IFN)/ribavirin (RBV) resistance-determining region (IRRDR) and the IFN sensitivity-determining region (ISDR)] on the outcome of pegylated IFN and RBV (PEG-IFN/RBV) treatment.
  
  
  METHODS
  Sixty-six patients infected with hepatitis C virus (HCV)-2a or HCV-2b who received PEG-IFN/RBV for 24 weeks were examined.
  
  
  RESULTS
  In HCV-2a, the major genotype of IL28B SNP showed a tendency toward association with sustained virological response (SVR) and rapid virological response (RVR), and four or more mutations in IRRDR (IRRDR[2a] ≥4) and one or more mutations in ISDR plus its carboxyl-flanking region (ISDR/+C[2a] ≥1) were significantly associated with SVR and RVR. In HCV-2b, one or more mutations in the N-terminal part of IRRDR (IRRDR/N[2b] ≥1) were significantly associated with RVR. Multivariate analysis identified the major genotype of IL28B SNP and IRRDR[2a] ≥4 as independent predictive factors of SVR in HCV-2a, with IRRDR[2a] ≥4 being more powerful than the IL28B SNP. Also, IRRDR[2a] ≥4 in HCV-2a and IRRDR/N[2b] ≥1 in HCV-2b were significant determiners of RVR.
  
  
  CONCLUSIONS
  The NS5A sequence heterogeneity and IL28B SNP are useful factors to predict the sensitivity to PEG-IFN/RBV therapy in HCV-2a and HCV-2b infections.
authors.affiliation: Department of Gastroenterology, Kobe Asahi Hospital, Kobe, Japan.
authors.forename: Soo Ryang
authors.initials: SR
authors.lastname: Kim
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Shamy
authors.forename: Susumu
authors.initials: S
authors.lastname: Imoto
authors.forename: Ke Ih
authors.initials: KI
authors.lastname: Kim
authors.forename: Kayo
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Soo Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Hatae
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Aya
authors.initials: A
authors.lastname: Fujinami
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.forename: Hak
authors.initials: H
authors.lastname: Hotta
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003710:Demography; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007378:Interleukins / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000737:chemistry; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D019562:Viral Load / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics; D000095022:Interferon Lambda; D012324:RNA-Dependent RNA Polymerase
chemical_list: D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase