title: Helper T cell cytokine response to ribavirin priming before combined treatment with interferon alpha and ribavirin for patients with chronic hepatitis C.
abstract: The viral genotype and serum viral level influence the response to interferon (IFN) treatment in patients with chronic hepatitis C virus (HCV) viremia. The aim of this study was to investigate a possible relationship between early virological response and helper T (Th) cell cytokine expansion by 4 weeks of ribavirin (RIB) alone followed by IFN and RIB combined in patients with genotype 1b and a high HCV RNA level, patients reported not to respond well to IFN treatment. Eighty-one patients with genotype 1b and a high HCV RNA level, over 100 international unit per milliliter (KIU/mL) (by Amplicor HCV Monitor), were assigned to two groups: Group A (N = 40) with a 4-week RIB administration followed by a 24-week combination treatment, and Group B (N = 41) with a 24-week combination treatment only. Blood was obtained from each patient on the following schedule: at Baseline (4 weeks before day 0), on day 0 (initiation day of the RIB and IFN combination treatment), weeks 4 (4 weeks after the start of the combination treatment), and at the end of the combination treatment. Flow cytometry was used to investigate sequential changes of IFN-gamma producing (Th1) and interleukin-4 producing (Th2) cells from whole blood samples after stimulation with PMA and ionomycin. Serum HCV RNA clearances were 32.5% at week 4, 43.2% at week 8, 85.7% at the end of the combination treatment, and 22.9% within the 24-week follow-up in Group A; and 17.1%, 27.0%, 66.7% and 19.4% in Group B, respectively. The mean Th1/Th2 ratio significantly increased from 15.9 at baseline to 17.6 at day 0 with a decrease of Th2 cells, and then significantly decreased from 17.6 at day 0 to 15.5 at week 4 in Group A, while there was no significant change in Group B between baseline and day 0. In Group A, 13 patients with HCV RNA clearance within 4 weeks had a significantly increased Th1/Th2 ratio, from 14.0 at baseline to 22.1 at day 0, and then a significantly decreased ratio, from 22.1 at day 0 to 15.0 at week 4, while the others had no significant change in the ratio. RIB administration preceding combined treatment of RIB with IFN was more effective in Th2 cell expansion than the usual combined treatment of IFN with RIB and led to a relatively early virological clearance in chronic hepatitis C patients with genotype 1b and a high HCV RNA level.
authors.affiliation: Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka 812-8582, Japan. furusyo@genmedpr.med.kyushu-u.ac.jp
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kubo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeoka
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nabeshima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin