Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis

Abstract

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN.

Viral Glomerulopathy

“…MN has also been described, but the causative relationship is relatively unclear [ 44 , 45 ]. In rare cases, hepatitis C can cause ANCA-associated GN [ 46 ]. Mixed cryoglobulinemia is associated with HCV infection in about 10–70% of patients [ 47 ] and usually presents as type 2 (polyclonal IgG and monoclonal IgM) and rarely type 3 (polyclonal IgG and IgM) cryoglobulinemia.…”

Antineutrophil cytoplasmic antibody-associated vasculitis, update on molecular pathogenesis, diagnosis, and treatment

“…37 In selected patients, for whom malignancy may be a concern, mycophenolate may still be an effective and safe option for the maintenance of remission. 5 The use of methotrexate was discussed earlier and presents another popular option for remission maintenance. 14,27,35 It is important to note that proteinuria control was inferior with the use of methotrexate compared to that of cyclophosphamide.…”

“…Hepatitis C has also been associated with GPA, as well as MPA albeit rarely. 5 Some medications have also been noted to induce AAV, and propylthiouracil (PTU) has been reported as a drug linked to both PR3 and MPO ANCA seropositivity (MPO-ANCA being more common). However, only small percentage of these patients develops clinical vasculitis.…”