title: Antigen-specific T lymphocyte proliferation decreases over time in advanced chronic hepatitis C.
abstract: To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5-6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long-term PEG-IFN treatment.
authors.affiliation: Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA 98109, USA. chihiro@u.washington.edu
authors.forename: C
authors.initials: C
authors.lastname: Morishima
authors.forename: A M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: A L
authors.initials: AL
authors.lastname: Rothman
authors.forename: H L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: K L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: W M
authors.initials: WM
authors.lastname: Lee
authors.forename: M J
authors.initials: MJ
authors.lastname: Koziel
authors.forename: R J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: H-Y
authors.initials: HY
authors.lastname: Kim
authors.forename: E C
authors.initials: EC
authors.lastname: Wright
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000008:administration & dosage; D002175:Candida / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006651:Histocytochemistry; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology; D013997:Time Factors
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013744:Tetanus Toxin; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a