Prospective study of viral clearance and CD4(+) T-cell response in acute hepatitis C primary infection and reinfection.

BACKGROUND: The outcome of acute hepatitis C is determined by early host-virus interactions, particularly involving the antiviral T-cell response. OBJECTIVES: To identify early prognostic markers of spontaneous resolution of acute hepatitis C by performing a comprehensive analysis of viral and immunological factors during the natural course of acute HCV infection and reinfection. STUDY DESIGN: 20 patients were investigated prospectively during acute HC or confirmed reinfection and 18 of them during follow up after spontaneous or treatment-induced elimination of the virus and resolution of the disease. Multiparameter flow cytometry was used to functionally characterize virus-specific CD4(+) T-cell responses relative to the virologic outcome. RESULTS: Parallel immunologic and virologic monitoring of patients with acute HC identified distinct patterns of host-virus interaction related to HCV persistence or clearance. The highest frequency of antiviral Th1 cytokine-producing CD4(+) T-cells was observed in patients with HCV reinfection, preceding rapid viral clearance within 3 weeks after disease onset. In all patients who subsequently cleared viremia, CD4(+) T-cells produced Th1 cytokines following stimulation with non-structural HCV antigens (NS3 and NS4). In contrast, a chronic course of disease was associated with the absence of antiviral Th1 cytokine producing cells from the first weeks after onset of disease (acute persistent HC), or with fluctuating RNA levels (yo-yo pattern) and gradual waning of antiviral Th1 cells. CONCLUSIONS: The results highlight the variability of immune response pattern in acute hepatitis C. Most importantly, "acute persistent hepatitis C" and a lack of TH1 effector cells within the first months of acute hepatitis C represent efficacious predictors of viral persistence and could thus be used as criteria in selecting candidates for early antiviral treatment.