Impact Of Virus Specific T Cell Responses On Chronically HCV-1b Infected Patients Receiving Interferon-Free Direct-Acting Antiviral Agents(DAAs)Therapy

Aim: This study conducted research on chronically HCV-1b infected patients who accepted IFN-free DAAs therapy to observe whether the HCV-specific T cell responses can be reconstituted in the course of treatment.Methods: This experiment in total recruited 20 chronically HCV-1b infected patients from two clinical drug trials regarding hepatitis C direct-acting antiviral treatments.Nine previously treatment naive patients came from AI447-114 clinic trial: 24 weeks interferon free therapy with daclatasvir plus asunaprevir.The rest were from M13-767 clinical test: 12 weeks interferon free treatment with compound preparation of paritaprevir,ritonavir,ombitasvir plus dasabuvir,some of these patients had received a traditional interferon(IFN)and ribavirin(RBV)combination therapy.We tracked and detected patients' aminotransferase levels and viral load at different time points,at the same time,collected patients' peripheral blood samples and separated peripheral blood mononuclear cells(PBMCs).We used a total of 376 polypeptide which covering the HCV-1b complete sequence to stimulate PBMCs.And then,ELISPOT assay was conducted to detect the secretion level of HCV specific IFN-? along with DAAs therapy.Results:HCV viral load of all patients declined precipitously after the first week of treatment,the vast majority of patients decreased below detection limit after 4 weeks of therapy.Only 1 patient had occurred virologic breakthrough after 16 weeks of treatment.As the change of virus quantity,ALT and AST levels from the most patients of two clinical tests also declined sharply after the first week of treatment,and basically recovered to normal range after 2 weeks.In both clinical trials,HCV specific IFN-?production remained on a relatively low level and did not show much variety along with the whole therapy at each time point.Conclusions: The early HCV specific T cell responses from chronically HCV-1b infected patients could not be restored,even after rapid viral clearance by IFN-free DAAs therapy.