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Hepatitis C virus-associated mixed cryoglobulinaemia 

Hepatitis C virus-associated mixed cryoglobulinaemia
Hepatitis C virus-associated mixed cryoglobulinaemia

Edgar D. Charles

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date: 27 September 2020

1. HCV-related cryoglobulins contain RF, polyclonal IgG and HCV RNA that precipitate and deposit on vascular endothelium, causing an end-organ vasculitis predominantly in skin, kidneys and peripheral nerves.

2. Patients often have striking clonal expansions of RF-bearing memory B cells with restricted usage of RF-encoding Ig gene segments. Most of these activated B cells have low to moderate levels of somatic hypermutations that suggest an immunological response to antigenic stimulation.

3. A smaller subset of patients with MC develop a low-grade NHL comprising B cells that are immunophenotypically similar to the expanded B cells seen in MC. The antigenic dependence of these B cells is supported by evidence that HCV-related MC and NHL disappear after successful treatment of HCV infection.

4. Treatment of HCV-related MC should aim to eradicate HCV infection. MC symptoms almost always resolve within 6 months of successful virological clearance. However, patients who are unlikely to tolerate or benefit from anti-HCV therapy may be offered symptomatic therapy with immunosuppressives (e.g. rituximab, corticosteroids or cyclophosphamide) or plasmapheresis.

5. Continued patient-centred studies are necessary to elucidate the pathogenesis of HCV MC and to devise improved therapeutic strategies for affected patients.

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