A case of rapid amelioration of hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis treated by interferon-free directly acting antivirals for HCV in the absence of immunosuppressant

Abstract

Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection. The standard therapy of a chronic HCV infection is IFN monotherapy or IFN combined with ribavirin; however, after the introduction of direct-acting antivirals (DAAs), the standard therapy for patients with HCV genotype 1 has dramatically changed. We report a case of HCV-associated cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir, which are IFN-free DAAs for HCV, in combination with angiotensin II receptor blocker without immunosuppressive therapy. The patient developed severe nephrotic syndrome with progressive kidney dysfunction. Blood examination revealed a high copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia of IgM-κ, and hypocomplementemia. Histological analysis showed MPGN type 1. These findings were compatible with those observed in HCV-associated cryoglobulinemic MPGN. This case offers original evidence for the application of newer generation of IFN-free DAAs in the treatment of HCV-associated cryoglobulinemic nephropathy.

Keywords: Cryoglobulinemic membranoproliferative glomerulonephritis; Hepatitis C virus; Interferon-free direct-acting antiviral agents.

Fig. 1

Pathological findings. Pathological findings show the characteristic features of an MPGN type 1. Mesangial expansion with lobular formations (a), mesangial interposition (arrow in b), and double-contour appearance of the capillary wall (arrow head in b) in glomeruli were observed by PASM-HE stain. Electron micrograph showed subendothelial electron-dense deposits (arrow in c and d) and expansion of subendothelial space (arrowhead in f). High magnification picture d and f are square in c and e, respectively. Immunofluorescence showed segmental deposits of IgG, IgM, C3, and κ along the glomerular capillary walls

Fig. 2

Clinical course. A couple of months prior to the first visit, abnormal urinary findings started to emerge, followed by the elevation of serum creatinine. HCV in the circulation cleared and AST normalized within two weeks after the initiation of DAA therapy, and hematuria and proteinuria dramatically improved with subsequent improvement of kidney function despite sustained cryoglobulinemia and hypocomplementemia. Semi-quantified cryoglobulin value decreased in parallel with the serum levels of IgM and RF, following HCV eradication. ND not detected