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Risultati sfruttabili
The characterization of HCV specific cellular and humoral immune response in patients with self-limited acute hepatitis C led to the identification of immune mechanisms which are associated with viral clearance. This knowledge forms the basis for the development of protective and therapeutic vaccines against hepatitis C.
Hepatitis C is a chronic viral infection of the liver that affects about 5 million Europeans and is one of the major causes of chronic liver disease, liver cirrhosis and liver cancer in Europe. Available therapies cure only about a third of patients and a vaccine is not yet available.
Within this project it was the aim to identify viral and immunological factors that contribute to viral clearance in those patients that have a self-limited course of acute hepatitis C. These studies should contribute to the development of preventive and therapeutic vaccines for chronic hepatitis C.
A large group of patients with acute hepatitis C were studied. About fifty percent of patients presenting with symptomatic acute hepatitis C resolved the infection spontaneously within six to ten weeks.
Studying the virus specific immune response it could be shown that a strong and maintained cellular immune response consisting of CD4+ T helper cells was associated with a self limited course of acute hepatitis C. In addition, a strong virus specific CD8+ T cell response was also detectable in the early phase of acute hepatitis C but, irrespective of disease outcome, was frequently lost a few months later. Nevertheless it is likely that act in concert with virus specific T Helper cells for efficient virus control.
Virus specific antibodies appeared early in the course of acute hepatitis C and apparently more rapidly in-patients who subsequently cleared the infection. However, these antibodies may not be virus neutralizing.
Sequencing the infecting viruses reveled that mutations developed early in the T cell recognition sites. Additional and more extensive studies are required, however, to clarify, whether the development of mutations contributes to viral persistence.
Although there are still many mysteries in the pathogenesis of chronic hepatitis C virus infection, the results of this collaborative study suggest that strong virus specific T cell response, consisting of both helper and cytotoxic T cells, is able to clear the infection. The therapeutic induction of such a T cell response could be a promising approach for the treatment of chronic hepatitis.
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