Persistent Cryoglobulinaemia After HCV Cure: Implications for Kidney Transplantation

Abstract

Direct-acting antivirals cure most patients with chronic hepatitis C virus (HCV) infection, but recovery from HCV-associated mixed cryoglobulinaemia is less uniform: clinical and immunologic responses may be incomplete, delayed or followed by relapse. Cryoglobulins, rheumatoid factor, hypocomplementaemia and residual B-cell clones frequently persist after sustained virologic response (SVR), and it is often unclear whether these findings reflect ongoing cryoglobulinaemic disease, slowly resolving immunologic abnormality or, where organ dysfunction persists, irreversible chronic damage. The distinction is consequential in kidney transplant candidates, in whom persistent abnormalities may raise concern about transplant timing, recurrent cryoglobulinaemic glomerulonephritis (CryoGN) and the use of pretransplant rituximab or plasma exchange, yet transplant-specific evidence is minimal.

This narrative review examines evidence relevant to individualised pretransplant assessment, prompted by a patient with advanced chronic kidney disease, persistent type II cryoglobulinaemia and predominantly chronic biopsy findings who sought advice about future transplantation. We distinguish direct transplant observations from non-transplant post-SVR data, treatment evidence for active disease, and expert-derived proposals. Direct evidence in HCV-cured patients with cryoglobulinaemic kidney disease is sparse, and comparative evidence for pretransplant immunomodulation for isolated serologic persistence is lacking. We propose an unvalidated expert framework comprising active disease, uncertain activity, and clinical remission with persistent serologic abnormalities; these are provisional clinical descriptions rather than validated risk categories or eligibility criteria. Assessment should centre on organ activity, clinically significant clonal disease and follow-up requirements. In our view, persistent serologic abnormalities alone, in the absence of objective organ activity or clinically significant clonal disease, should not be the determinant of transplant eligibility.