title: Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b.
abstract: A study was carried out to determine whether early viral dynamics retain prediction of the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on different genetic polymorphisms near the IL28B gene, the strongest baseline predictor of response to this therapy. A total of 272 patients infected with hepatitis C virus (HCV) genotype 1b were grouped according to genetic polymorphisms near the IL28B gene (rs8099917). The ability of reduced HCV RNA levels at 4 and 12 weeks after starting therapy to predict a sustained virologic response was evaluated based on these genotypes. Among patients with the TT genotype for rs8099917 (associated with a favorable response), the rates of sustained virologic response were higher in patients with a ≥3 log(10) reduction in serum HCV RNA levels at 4 weeks after starting therapy (P < 0.0001). In contrast, among patients with the TG/GG genotype (associated with an unfavorable response), there were no differences in this rate based on the reduction in HCV RNA levels at 4 weeks. Early viral dynamics at 4 weeks after starting therapy retains its predictive value for sustained virologic response in patients with the TT genotype for rs8099917, but not in patients with the TG/GG genotype. Patients who are likely to achieve sustained virologic response despite unfavorable TG/GG genotype cannot be identified based on early viral dynamics during therapy. In contrast, lack of early virologic response at 12 weeks retains a strong predictive value for the failure of sustained virologic response regardless of IL28B polymorphisms, which remains useful as a factor to stop therapy.
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. hmtoyoda@spice.ocn.ne.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Honda
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Katano
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda