HCV-Associated Nephropathies in the Era of Direct Acting Antiviral Agents

Abstract

Hepatitis C virus (HCV) infection is a systemic disorder that frequently associates with extrahepatic manifestations, including nephropathies. Cryoglobulinemia is a typical extrahepatic manifestation of HCV infection that often involves kidneys with a histological pattern of membranoproliferative glomerulonephritis. Other, less common renal diseases related to HCV infection include membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathy. Over the last decades, the advent of direct-acting antiviral therapies has revolutionized treatment of HCV infection, dramatically increasing the rates of viral clearance. In patients where antiviral therapy alone fails to induce renal disease remission add-on B-cell depleting agents represent an alternative to counteract the synthesis of pathogenic antibodies. Immunosuppressive therapies, such as steroids, alkylating agents, and plasma exchanges, may still represent an effective option to inhibit immune-complex driven inflammatory response, but the potentially associated increase of HCV replication and worsening of liver disease represent a serious limitation to their use.

Keywords: HCV; cryoglobulinemia; direct acting antivirals; kidney transplant; rituximab.

Figure 1

Mechanism of HCV-Induced Cryoglobulinemic Nephropathy. HCV infection of B cells leads to the production of IgM with rheumatoid factor (RF) activity that bind HCV-IgG immune-complexes. These cold-precipitable multimolecular immune-complexes deposit in the subendothelial space and in the mesangium, where they activate classical complement pathway. This leads to the formation of C3a and C5a anaphylatoxins that recruit and activate inflammatory cells and to the deposition of membrane attack complex (MAC) on the endothelium that activates endothelial cell proinflammatory functions.