title: Intrahepatic and peripheral blood virus-specific cytotoxic T lymphocyte activity is associated with a response to combination IFN-alpha and ribavirin treatment among patients with chronic hepatitis C virus infection.
abstract: This report describes an association between intrahepatic and peripheral blood cytotoxic T lymphocytes (CTL) activity present prior to receiving treatment, and a response to combination interferon-alpha (IFN-alpha) and ribavirin therapy for chronic hepatitis C virus (HCV) infection. Recombinant vaccinia virus constructs were used to expand and detect cytotoxic effectors against the entire genotype 1a HCV polyprotein. Six patients with a sustained response to therapy were significantly more likely to display intrahepatic and peripheral blood HCV-specific CTL activity than patients who relapsed or had no treatment response. Limited longitudinal data suggested that rather than combination therapy acting to enhance the CTL response to achieve viral clearance, detectable CTL prior to treatment increases the likehood of the host responding to the direct antiviral activity of IFN-alpha and ribavirin.
authors.affiliation: Department of Pathology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia. freemanto@sesahs.nsw.gov.au
authors.forename: A J
authors.initials: AJ
authors.lastname: Freeman
authors.forename: G
authors.initials: G
authors.lastname: Marinos
authors.forename: R A
authors.initials: RA
authors.lastname: Ffrench
authors.forename: A R
authors.initials: AR
authors.lastname: Lloyd
mesh_terms: D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008111:Liver Function Tests; D008213:Lymphocyte Activation; D008297:Male; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin