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

Authors: Jirillo, E.; Pellegrino, N.M.; Piazzolla, G.; Caccavo, D.; Antonaci, S.

Source: Current Pharmaceutical Design, Volume 6, Number 2, 1 January 2000 , pp. 169-180(12)

Publisher: Bentham Science Publishers

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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

Document Type: Review article

DOI: 10.2174/1381612003401271

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