Persistence of monoclonal B‐cell expansion and intraclonal diversification despite virus eradication in patients affected by hepatitis C virus‐associated lymphoproliferative disorders

Summary We investigated 23 hepatitis C virus (HCV)‐infected patients with overt lymphoproliferative diseases (15 cases) or monoclonal B lymphocytosis (8 cases) treated with direct agent antiviral (DAAs) per clinical practice. DAA therapy yielded undetectable HCV‐RNA, the complete response of cryoglobulinemia vasculitis and related signs, whilst the presence of B‐cell clones (evaluated by flow cytometry, IGHV, and BCL2‐IGH rearrangements), detected in 19/23 cases at baseline, was maintained (17/19). Similarly, IGHV intraclonal diversification, supporting an antigen‐driven selection mechanism, was identified in B‐cell clones at baseline and end of follow‐up. DAA therapy alone, despite HCV eradication and good immunological responses, was less effective on the pathological B‐cell clones.