Association between HCV amino acid substitutions and outcome of peginterferon and ribavirin combination therapy in HCV genotype 1b and high viral load.
OBJECTIVE
We prospectively compared the sensitivity to interferon (IFN) and the efficacy of antiviral combination therapy with peginterferon (PEG-IFN) and ribavirin for chronic hepatitis C virus (HCV) genotype 1b infection according to the amino acid sequences of the HCV core, E1, and NS5A regions reported to be associated with the outcome of antiviral therapy.


METHODS
A total of 107 patients with HCV genotype 1b were investigated. All patients received combination therapy with PEG-IFN alpha-2b and ribavirin. Amino acids 70 and 91 (core), 139 (E1), and 2209-2248 (NS5A) of HCV were analyzed by direct nucleotide sequencing.


RESULTS
The reduction in HCV RNA concentration at 24 h after a single administration of conventional IFN-alpha and after the start of combination therapy was significantly less marked, and rates of complete early virologic response, end-of-treatment response, and sustained virologic response (SVR) were significantly lower (all P < 0.0001) in patients with glutamine at amino acid 70 (n = 29) than in those with arginine at that position (n = 70). We found no differences associated with the other amino acid positions. Amino acid 70 was an independent factor for the responses to the therapy in multivariate analysis.


CONCLUSIONS
The identity of amino acid 70 of the HCV core region affected the sensitivity to IFN; patients with glutamine at amino acid 70 of HCV showed resistance to IFN. Consequently, it strongly affected the outcome of combination therapy with PEG-IFN and ribavirin in Japanese patients with HCV genotype 1b.
Toyoda
Hidenori
H
Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan. hmtoyoda@spice.ocn.ne.jp
Kumada
Takashi
T
Tada
Toshifumi
T
Arakawa
Takahiro
T
Hayashi
Kazuhiko
K
Honda
Takashi
T
Katano
Yoshiaki
Y
Goto
Hidemi
H
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001706:Biopsy; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D017423:Sequence Analysis, RNA; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a