title: T-cell response relative to genotype and ethnicity during antiviral therapy for chronic hepatitis C.
abstract: Viral genotype and host ethnicity are important predictors of viral clearance during antiviral therapy for chronic hepatitis C virus (HCV) infection. Based on the role of T cells in natural HCV clearance, we hypothesized that T cells may contribute to the genotypic and ethnic difference in treatment outcome. To test this hypothesis, T-cell response to HCV antigens (core, nonstructural NS3/4 and NS5) and control phytohemagglutinin (PHA) was monitored prospectively and was correlated with virological outcome in 41 patients chronically infected with HCV (27 genotype 1, 14 genotype 2 or 3; 19 black persons, 22 white persons) undergoing combined interferon alfa and ribavirin therapy. Interestingly, in patients with genotype 2 or 3 infection, enhanced virological response coincided with a greater T-cell response to HCV NS3/4 antigen at baseline (50% vs. 15%; P = .026) that augmented further during therapy (29% vs. 4%; P = .035) compared with genotype 1-infected patients. However, HCV-specific T-cell response remained weak in genotype 1-infected patients regardless of virological outcome or ethnicity. Furthermore, virological outcome was associated with a suppressed baseline proliferative response to phytohemagglutinin (P < .03) that increased during therapy (P < .003) independent of ethnicity or genotype. In conclusion, HCV-specific T-cell response was associated with HCV genotype but not with therapeutic clearance of HCV infection. The association between treatment outcome and phytohemagglutinin response suggests more global and antigen-nonspecific mechanisms for therapeutic HCV clearance.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Kaplan
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Jason
authors.initials: J
authors.lastname: Stadanlick
authors.forename: Mary
authors.initials: M
authors.lastname: Valiga
authors.forename: Kirti
authors.initials: K
authors.lastname: Shetty
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Kyong-Mi
authors.initials: KM
authors.lastname: Chang
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D044383:Black People / Q000235:genetics; D018791:CD4 Lymphocyte Count; D049109:Cell Proliferation / Q000187:drug effects; D005838:Genotype; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D044465:White People / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D010835:Phytohemagglutinins; D012254:Ribavirin