title: Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy.
abstract: Patients with low titer (<0.5 mEq/ml) of hepatitis C virus (HCV) genotype 2a achieve high and sustained response (SR) rates to interferon (IFN) monotherapy, but we also encounter patients who are resistant to therapy. We explored the relationship between response to IFN and virological differences in such patients. We evaluated 159 consecutive naive patients with low titer of HCV genotype 2a who received IFN monotherapy. A case-control study matched for age, sex, and viral load was conducted to examine the substitution patterns in amino acid positions (amino acids) 2163-2254 of nonstructural (NS) 5A between nonresponders to ideal IFN dose (>/=500 million units) (nonresponders; NR) and responder to less than ideal dose. Overall, 82.4% achieved SR. The substitution numbers in amino acids 2193-2254 were higher in SR than NR patients (P < 0.05). High proportions of patients with substitution at amino acid 2205 (mainly threonine [T] instead of alanine [A]), dual amino acids 2169 and 2205 (mainly A-T instead of T-A), and those without substitution at amino acids 2227 were NR (P < 0.05). Four of 7 NR patients achieved SR after receiving a second course of IFN. Their amino acids patterns at positions probably associated with sensitivity to IFN did not change at the start of initial and second therapies except for one patient, and they had lower viral load and were treated with higher IFN dose in the second course compared with the initial course. Our results suggest that substitution patterns in NS5A in patients with low titer of HCV genotype 2a may affect their response to IFN, but the response to therapy may be affected by mechanisms other than substitutions in this region.
authors.affiliation: Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Someya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase