Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cellresponse in acute hepatitis C

Background & Aims: The prospective comparison of patients with acute hepati tis C virus (HCV) who spontaneously clear the virus with those who cannot a chieve viral elimination and progress to chronic hepatitis offers the uniqu e opportunity to analyze natural mechanisms of viral elimination. Methods: We studied the HCV-specific CD4(+) T-cell response in 38 patients with acut e HCV and correlated the clinical course with the antiviral immune response . The individual HCV-specific T-cell response was assessed in a proliferati on assay (H-3-thymidine uptake) and an enzyme-linked immunospot assay. Resu lts: Patients were classified according to their clinical course and patter n of CD4(+) T-cell responses in 3 categories: first, patients mounting a st rong and sustained antiviral CD4(+)/Th1(+) T-cell response who cleared the virus (HCV RNA-negative; n = 20); second, patients who were unable to mount an HCV-specific CD4(+) T-cell response and developed chronic disease (n = 12); and third, patients who initially displayed a strong CD4(+) T-cell res ponse and eliminated the virus (HCV PCR-negative) but subsequently lost thi s specific T-cell response (n = 6), The loss of the HCV-specific CD4+ T-cel l response was promptly followed by HCV recurrence. Conclusions: The result s indicate that a virus-specific CD4(+)/Th1(+) T-cell response that elimina tes the virus during the acute phase of disease has to be maintained perman ently to achieve long-term control of the virus. The induction and/or maint enance of virus-specific CD4(+) T cells could represent a promising therape utic approach in HCV infection.