Hepatitis C Virus Associated Glomerulonephritis

IntroductionApproximately 170 million persons worldwide are infected with the hepatitis C (HCV) virus.The incidence of glomerulonephritis in HCV-infected patients is unknown due to a lack of large-scale cross sectional surveys however subclinical renal involvement is believed to be highly prevalent among patients with HCV hepatitis.The most common HCVassociated glomerulonephritis is membranoproliferative glomerulonephritis (MPGN) type 1 with or without cryoglobulinaemia.MPGN typically presents several years, and often decades, after initial infection with HCV.Most patients have laboratory evidence of hypocomplementaemia, circulating rheumatoid factors, and cryoglobulinaemia.Other uncommon forms of glomerular disease that have been reported to be associated with HCV infection include membranous nephropathy, IgA nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis/immunotactoid glomerulopathy, pauciimmune glomerulonephritis, and thrombotic microangiopathy.The principal clinical manifestations of glomerular disease in HCV patients are the presence of proteinuria and microscopic haematuria with or without impaired kidney function.The clinical course of these HCV-associated glomerulopathies is generally characterised by remission and relapsing phases.The overall prognosis for HCV-associated glomerulonephritis remains poor, not only because of renal disease progression but because of the high incidence of cardiovascular disease, infection and hepatic failure.The exact pathogenic sequence of injury that results in glomerulonephritis is not known.The prevailing theory is that glomerular injury results from deposition of circulating immune complexes that contain HCV antigens and anti-HCV antibody.Involvement of the innate immune system in HCV-associated MPGN has been suggested with demonstration of upregulation of Toll-like receptor 3. In establishing a link between HCV infection and the immune response targeting the glomerulus, antiviral, plasma exchange and immunosuppressive therapies have been used in patients.The use of antiviral therapy in HCV-positive patients with glomerulonephritis is targeted at eliminating the virus and reducing the generation of HCV-related antibodies and immune complexes.The data to support antiviral treatment for HCV-associated glomerulonephritis is limited, however interferon therapy may be superior to www.intechopen.comAn Update on Glomerulopathies -Clinical and Treatment Aspects 170 immunosuppressive agents in HCV-associated cryoglobulinaemic glomerulonephritis in lowering proteinuria.Agents such as rituximab have also been shown to be efficacious in the treatment of HCV-associated cryoglobulinaemic glomerulonephritis.This chapter provides the reader with an overview of hepatitis C-associated glomerulonephritis that covers epidemiology, clinical manifestations, natural history, immunopathophysiology, and a review of the evidence underpinning current therapeutic approaches.Hepatitis C virus (HCV) is a leading cause of chronic liver disease in the world.The World Health Organization estimates that there are 170 million individuals with HCV infection and an incidence of 3-4 million new cases per year (WHO, 2000).HCV infection leads to chronic liver disease, but also to extra-hepatic manifestations.These include mixed cryoglobulinaemia, lymphoproliferative disorders and renal disease.HCV infection has been reported in association with distinct histological patterns of glomerulonephritis.In this review, we will canvass the epidemiology, clinical manifestations, natural history, immunopathophysiology, and current therapies of HCV-associated glomerulonephritis, as well as cover issues around renal transplantation.