title: Kinetic response of wild and mutant core codon 70 strains of HCV genotype 1b to pegylated interferon-α and ribavirin therapy.
abstract: BACKGROUND
  Amino acid (aa) 70 substitution (R70Q/H) in the core protein of hepatitis C virus (HCV) genotype 1b has been shown to be one of the key factors in determining resistance for pegylated interferon-α plus ribavirin combination therapy (PEG-IFNα/RBV). But the exact mechanisms remain unclear. The aim of this study was to investigate the dynamic response of wild and mutant core codon 70 strains to PEG-IFNα/RBV treatment.
  
  
  METHODS
  One hundred twelve Chinese patients with chronic HCV 1b infection were enrolled and received a standard protocol of 48 weeks of PEG-IFNα/RBV therapy and 24 consecutive weeks of follow-up. Serial blood samples were obtained at pretreatment baseline, and again at weeks 2, 4, 8, 12, and 24 during therapy for the quantification of 70R and 70Q/H strains. Dynamic characteristics and association with early virological response (EVR), sustained virological response (SVR) and IL28B genotypes were analyzed.
  
  
  RESULTS
  Of the 112 patients enrolled in this study, 93.8% (105/112) were infected with mixture of 70R and 70Q/H strains before treatment. The 70Q/H strain was dominant in 20.5% of patients. 42.9% of patients with dominant 70Q/H exhibited EVR versus 88.6% of patients with dominant 70R (P < 0.001). Furthermore, 35.0% of patients with dominant 70Q/H exhibited SVR versus 77.4% with dominant 70R (P < 0.001). However, regardless of the dominant strain, virological response types or the IL28B SNP genotypes, 70Q/H strains always exhibited the same response to treatment as the 70R strains and the percentage of HCV harboring the 70Q/H substitution did not change significantly during treatment.
  
  
  CONCLUSIONS
  Although the ratio of 70Q/H to 70R is related to the virological response, 70Q/H strains always exhibited the same response as the 70R strains during PEG-IFNα/RBV treatment. Substitution of R70Q/H alone is not enough to lead to resistance to therapy. Positive selection for 70Q/H induced by IFNα was not observed.
authors.affiliation: Department of Hepatitis C & Toxic liver diseases, Beijing Youan Hospital, Capital Medical University, Beijing, the People's Republic of China. yfcyt@139.com.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Management center of medical record, Beijing Youan Hospital, Capital Medical University, Beijing, the People's Republic of China. lyhzj2006@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Hepatitis C & Toxic liver diseases, Beijing Youan Hospital, Capital Medical University, Beijing, the People's Republic of China. jslygxc@sina.com.
authors.forename: Lixia
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Hepatitis C & Toxic liver diseases, Beijing Youan Hospital, Capital Medical University, Beijing, the People's Republic of China. yunji8131@sina.com.
authors.forename: Zuopeng
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Hepatitis C & Toxic liver diseases, Beijing Youan Hospital, Capital Medical University, Beijing, the People's Republic of China. shuqing4000@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Nie
authors.affiliation: Department of Hepatitis C & Toxic liver diseases, Beijing Youan Hospital, Capital Medical University, Beijing, the People's Republic of China. cat216@163.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Liang
authors.affiliation: Beijing Youan Hospital, Capital Medical University, No. 8 Xitoutiao, Youanmenwai, Fengtai District, Beijing, 100069, the People's Republic of China. jinronghua321@sina.com.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage*; D001769:Blood / Q000821:virology; D002681:China; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000008:administration & dosage*; D012641:Selection, Genetic; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012254:Ribavirin