Polyclonal and monoclonal B lymphocytes response in HCV-infected patients treated with direct-acting antiviral agents

Hepatitis C Virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all-cause mortality. In this study we used flow cytometry to evaluate the effect of Interferon-free antiviral treatment on peripheral blood lymphocytes in HCV patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes were performed at baseline and at the end of treatment. In HCV infecteded patients with lymphoproliferative disorders s we evaluated Immunoglobulin (Ig) light chain κ/λ ratio variations as a measure of monoclonal B-cell response to antiviral therapy. Healthy volunteers were enrolled as controls. A total of 29 patients were included, 9 with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29/29 patients. We observed a significant reduction of the B-cell compartment (39% global reduction) in eight out of nine HCV patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV patients without lymphoproliferative disorders (9% global reduction). Among HCV patients with lymphoproliferative disorders, three showed an improvement/normalization of the Ig light chain ratio, whereas in the remaining six patients monoclonal B-cells persisted to be clonally restricted even one year after the end of treatment. Our data show that DAAs treatment can be effective in reducing the frequency of pathological B-cells in the peripheral blood of HCV patients affected by HCV-associated lymphoproliferative disorders, however monoclonal populations can persist after viral eradication. This article is protected by copyright. All rights reserved.