Hepatitis C Virus Infection: Immune Responsiveness and Interferon-a Treatment

E.   initial   Jirillo; N.   M.   Pellegrino; G.      Piazzolla; D.      Caccavo; S.      Antonaci

Abstract

Hepatitis C virus (HCV) is responsible for most cases of posttransfusion hepatitis and sporadic or community-acquired non-A, non-B hepatitis. Different generations of enzyme-linked immunosorbent assay have been generated for detecting antibodies to HCV epitopes. HCV-RNA quantitative analysis has been developed by means of polymerase chain reaction technique. This approach is the only reliable method for HCV-RNA tissue localization, being helpful in early diagnosis. HCV infected liver is characterized by an inflammatory infiltrate including CD4positive, CD8positive, and B lymphocytes. Evidence has been provided that in HCV patients CD8positive cell response is associated with low level of viraemia and higher level of disease activity. CD4positive T cells exhibit specificity for the core antigen, also correlating with disease activity and viraemia. Costimulatory molecules, cytokines, oxygen radicals, the complex Fas - Fas-ligand and soluble class I HLA structures are discussed as putative cofactors involved in disease evolution. Various forms of interferon (IFN)-alpha have been evaluated for the treatment of patients with HCV infection. Initial enthusiasm has been attenuated by the evidence of a low sustained virological response rate and the constant side effects of IFN-alpha therapy in patients with chronic HCV disease. Among possible markers for predicting therapeutic outcome in HCV-positive individuals, anti-core antibodies correlate positively with response to IFN-alpha administration, as well as reduction of interleukin-2 serum levels has been detected in patients with a good therapeutic response. Association between HCV infection and autoimmune phenomena, also in relation to IFN-alpha therapy has been reported. Finally, results of the combined treatment with IFN-alpha/ribavirin are illustrated.

Keywords: Hepatitis C Virus Infection, Immune Responsiveness, Interferon, HCV RNA, CD4 CD8 B lymphocytes, viraemia, fas ligand, IFN, HIV, cDNA clone, nonstructural NS domains, NS proteins NS2 NS5, HCV transmission, immunosorbent assay ELISA, enzyme linked, host immune response, Granulocyte macrophage colony, interferon IFN, interleukin, CTLs, Intraheptic B lymphocytes, recombinant vaccinia viruses VV, Innate Immunity, Arachidonic acid metabolites, soluble mediators, cytokines, ICAM 1, MHC CD80 CD86, TH1, TH2