title: Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene.
abstract: An association has been reported between genetic polymorphism near IL28B gene and the prevalence of mutation of hepatitis C virus (HCV) core region residue 70, both of which have been associated with a lack of virologic response to antiviral combination therapy with peginterferon (PEG-IFN) and ribavirin. This study investigated whether PEG-IFN/ribavirin combination therapy induces amino acid (AA) mutation at residue 70 of HCV and whether genetic polymorphism near IL28B gene affects it. AA substitutions at residue 70 of the HCV core region were measured and compared before and after combination therapy in 65 non-responders and 88 relapsers to the combination therapy. In three patients in whom both wild-type AA (arginine) and mutant-type AA (glutamine or histidine) were detected at residue 70 before treatment, only mutant-type AA was identified after treatment. In two patients who had wild-type AA solely before treatment, both wild-type and mutant-type AAs were identified at residue 70 after treatment. In five patients, in whom the AA had changed at residue 70 between before and after treatment, four patients carried the TT genotype at a polymorphic locus (rs8099917) near the IL28B gene and one carried the TG/GG genotype. No difference was found in the prevalence of this change of AA at residue 70 between the TT and the TG/GG genotype. Antiviral combination therapy with PEG-IFN and ribavirin does not appear to induce mutation of HCV core region residue 70 regardless of genetic polymorphism near the IL28B gene in Japanese patients infected with HCV genotype 1b.
authors: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. hmtoyoda@spice.ocn.ne.jp
authors: Hidenori
authors: H
authors: Toyoda
authors: Takashi
authors: T
authors: Kumada
authors: Kazuhiko
authors: K
authors: Hayashi
authors: Takashi
authors: T
authors: Honda
authors: Yoshiaki
authors: Y
authors: Katano
authors: Hidemi
authors: H
authors: Goto
authors: Takahisa
authors: T
authors: Kawaguchi
authors: Yoshiki
authors: Y
authors: Murakami
authors: Fumihiko
authors: F
authors: Matsuda
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D018936:Hepatitis C Antigens / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D018936:Hepatitis C Antigens; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D014758:Viral Core Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a