Treatment of hepatitis C cryoglobulinemia: Mission and challenges

Abstract

Mixed cryoglobulinemia (MC) is a syndrome resulting from cold-insoluble immunoglobulin complexes or cryoglobulins (CGs) that precipitate in the serum of 40% to 50% of patients with chronic hepatitis C virus (HCV) infection. The pathogenesis of cryoglobulinemia likely occurs due to chronic viremia and generation of rheumatoid factor following continuous presentation of antigen-immunoglobulin complexes to B cells. CGs are thought to be responsible for a variety of extrahepatic manifestations associated with HCV, including vasculitis, glomerulonephritis, arthritis, and neuropathies, which occur in approximately 10% of HCV patients with CGs. CGs also are a powerful predictive factor for progressive liver disease and the aggressive reoccurrence of liver disease in HCV-positive patients after liver transplantation. First-line therapy for MC due to HCV infection is antiviral therapy with pegylated interferon-alpha and ribavirin. Viral eradication usually produces marked reduction of physical complications and arrests end organ damage concomitant with clearance of CG. Additional prospective, controlled studies are necessary to determine whether CG influences patient virologic response and/or its durability to antiviral therapy. Immunomodulators such as corticosteroids and cyclophosphamide are efficacious for palliative treatment of the symptomatology of HCV cryoglobulinemia but may enhance viral replication. Consequently, prolonged therapy with immunomodulatory agents should be limited to severe vasculitis or aggressive glomerulonephritis in patients with MC due to HCV who have failed to respond to antiviral therapy. In acute, fulminant presentations, plasmapheresis may provide temporary relief and arrest the rapid progression of the disease so that additional therapy can be initiated.

Hepatitis C virus as a systemic disease: reaching beyond the liver

“… Reduced stroke risk [ 62 ]. Clearance of cryoglobulins with reduced risk of end organ damage [ 85 ]. …”

Cryoglobulinémie mixte symptomatique au cours de l’hépatite virale C

“…Les facteurs associés à la survenue de manifestations cliniques sont l'âge avancé, une infection chronique et surtout les caractéris-tiques de la cryoglobulinémie (type II, isotype IgM kappa, taux sériques élevés) [4][5][6][7][8][9][10][11][12][13][14][15][16]. Les manifestations cliniques les plus fréquentes sont cutanées, articulaires, neurologiques et rénales.…”

“…Des séances de plasmaphérèses peuvent être indiquées dans les manifestations rénales sévères isolées ou associées à des atteintes viscérales compromettant le pronostic vital. L'utilisation du cyclophosphamide, autrefois fréquente, est limitée par son efficacité inconstante et le risque infectieux lié à l'immunosuppression profonde qu'il engendre [4][5][6][7][8][9][10][11][12][13][14][15]. En cas de glomérulonéphrite membranoproliférative, l'utilisation d'un inhibiteur de l'enzyme de conversion ou un antagoniste des récepteurs de l'angiotensine est conseillée pour réduire la protéinurie [4].…”

Finally sofosbuvir: an oral anti-HCV drug with wide performance capability

“… 2 A smaller but significant number of infected patients also show extrahepatic complications such as mixed cryoglobulinemia, glomerulonephritis, arthritis, and some varieties of B-cell lymphoma. 3 Following exposure to HCV, only a minority of patients clear the acute infection, whereas 80% persist with life-long chronic viremia if not successfully treated. 4 The natural history of liver disease due to HCV is highly variable and profoundly influenced by patient cofactors such as type II diabetes, nontemperate alcohol consumption, fatty liver disease, and human immunodeficiency virus (HIV) coinfection.…”