Acute hepatitis C without and with schistosomiasis:: Correlation with hepatitis C-specific CD4+ T-cell and cytokine response

Background & Aims: Immune responses during the first few months of acute hepatitis C virus (HCV) infection seem crucial for viral control, but the relationship of these responses to natural history is poorly characterized. Methods: This prospective study investigated the HCV-specific CD4(+) and cytokine responses in patients with acute HCV hepatitis with or without Schistosoma mansoni coinfection, a parasitic infection with T helper (Th) 2 immune bias. HCV-specific CD4(+) proliferative responses and cytokine production in peripheral blood mononuclear cells were correlated with liver biopsy results at 6 months and at the end of follow-up. Results: Whereas 5 of 15 patients with HCV alone recovered from acute HCV, all (17 of 17) patients with S. mansoni coinfection progressed to histologically proven chronic hepatitis. Coinfected patients had either absent or transient weak HCV-specific CD4(+) responses with Th0/Th2 cytokine production. The magnitude of the HCV-specific CD4(+) response at week 12 was inversely correlated with the fibrosis progression rate in chronically infected patients. Conclusions: Patients with acute hepatitis C and schistosomiasis coinfection cannot clear viremia and show rapid progression once chronic infection is established. This rapid progression is associated with a strong Th2 response in peripheral immune responses, suggesting that early development of vigorous Th1 responses not only facilitates clearance but delays disease progression.