title: An early viral response to standard interferon-alpha identifies resistance to combination therapy with peginterferon and ribavirin in patients infected by HCV genotype 1.
abstract: As combination therapy with peginterferon (PEG-IFN) and ribavirin has a high morbidity, identifying individuals with hepatitis C virus (HCV) who will not respond to the treatment would be beneficial. The early responses of serum HCV RNA levels to standard interferon (IFN) and PEG-IFN were examined to determine if it was possible to identify resistance to combination therapy. One hundred thirty-one patients infected with HCV genotype 1b were enrolled. Patients were given 6 MU of standard IFN alpha-2b at least 2 weeks before initiating combination therapy. Serum HCV RNA levels were measured before, 24 hr after the administration of standard IFN, and 24 hr after the administration of PEG-IFN (at the start of the combination therapy). The association between reductions in HCV RNA levels at 24 hr after the administration of standard IFN and PEG-IFN and the outcome of combination therapy were analyzed. Reductions in HCV RNA levels were poorer in patients who did not respond than in those with a sustained virologic responses or relapses (P < 0.0001), both 24 hr after the administration of standard IFN and 24 hr after the administration of PEG-IFN. Reductions in HCV RNA levels 24 hr after the administration of standard IFN were an independent factor associated with non-response by multivariate analysis. An early reduction in viral load to a single administration of standard IFN is a useful predictor of non-response in patients with HCV genotype 1, allowing for pretreatment identification of patients who will not benefit from combination therapy.
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502 Japan. hmtoyoda@spice.och.ne.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.forename: Seiki
authors.initials: S
authors.lastname: Kiriyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanikawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hisanaga
authors.forename: Akira
authors.initials: A
authors.lastname: Kanamori
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tada
authors.forename: Makiko
authors.initials: M
authors.lastname: Takagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Takanori
authors.initials: T
authors.lastname: Hosokawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arakawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujimori
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007273:Injections, Intramuscular; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b