The course and therapy of acute hepatitis C viral infection. Is a prevention of its becoming chronic possible?

Abstract

Due to the large number of patients chronically infected with hepatitis C virus and not responding to combination therapy with interferon-alfa 2 and ribavirin new therapeutic regimens are required. Early treatment of the viral infection might improve the response, as seen in treatment of HIV infection, thereby preventing progression to chronicity. The article reviews the natural course of an acute HCV infection after different modes of transmission like i.v.-drug abuse, transfusion, needle stick injury and blood products. As there are no good animal models for HCV infection, models of an acute infection with other noncytopathic viruses might improve our understanding of the mechanisms of viral clearance. Results from an acute infection of mice with the lymphocytic chorionmeningitis virus are demonstrating the development of a T-cell tolerance by anergy or deletion of virus specific T-cells as possible mechanisms for the failure of the immune system to clear the virus. These findings are compared to the results of CD4+ and CD8+ T-cell responses in patients with acute HCV infection. Several clinical trials have demonstrated a benefit of an early treatment of HCV infection. Although the natural course of acute HCV is changing during the last few years, even recent trials indicate that progression to chronicity might be prevented by early therapy. The studies show that therapy could be improved by daily dosing, higher single doses of interferon compared and prolongation of therapy up to six month. As most patients with acute HCV infection are rather seen in an outpatient practise than in hospitals cases of acute infections should be collected and treatment protocols be standardized to confirm these results in prospective trials. First results in 21 patients show that viral clearance under therapy was achievable in all of the patients.