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

J Viral Hepat. 2017 Dec;24(12):1168-1176. doi: 10.1111/jvh.12746. Epub 2017 Aug 9.

Abstract

Hepatitis C virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinaemia 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-infected patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes was performed at baseline and at the end of treatment. In HCV-infected patients with lymphoproliferative disorders, 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, nine with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29 of 29 patients. We observed a significant reduction in the B-cell compartment (39% global reduction) in eight of nine HCV-infected patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV-infected patients without lymphoproliferative disorders (9% global reduction). Among HCV-infected patients with lymphoproliferative disorders, three showed an improvement/normalization of the immunoglobulin light chain ratio, whereas in the remaining six patients monoclonal B cells persisted to be clonally restricted even 1 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-infected patients affected by HCV-associated lymphoproliferative disorders; however, monoclonal populations can persist after viral eradication.

Keywords: DAAs; HCV; Lymphoma.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • B-Lymphocytes / immunology*
  • Female
  • Flow Cytometry
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology*
  • Humans
  • Immunity, Cellular*
  • Male
  • Middle Aged
  • Prospective Studies
  • Sustained Virologic Response

Substances

  • Antiviral Agents