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-j, 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.

Increased genomic instability following treatment with direct acting anti-hepatitis C virus drugs

“…Overall, the high expression of DNA repair genes that are involved in driving host inflammation could be implicated in long- term cryoglobulinemia relapses. Our data is consistent with work by Obata et al , 2017 showing complete remission of MCV after receiving DAA therapy without immunosuppressant, which was followed by cryoglobulinemia recurrence after 17 months from treatment initiation [ 76 ].…”

Symptomatic hyponatremia: a rare but reversible adverse reaction of lubiprostone

“…HCV-RNA turned out to be negative 6 months later. In contrast to the previous report,4 proteinuria still persisted >1 g/gCr and renal function (Cr, 6.5 mg/dL) further declined at 71 years of age. He developed renal anaemia (Hb, 10.1 g/dL) and was administered epoetin beta pegol monthly 5…”

Impact of sustained virologic response on chronic kidney disease progression in hepatitis C

“…Another explanation as to why achievement of SVR12 may not improve renal disease progression is that patients may have intrinsic renal disease prior to treatment, such as MPGN, and these patients will have CKD progression despite achieving SVR12; this has been previously described in the literature in case reports[ 24 ]. However, other reports have suggested that DAA therapy can result in successful treatment of HCV-associated MPGN with improvement in creatinine and proteinuria[ 25 ]. Furthermore, the patient population studied was unique - it is comprised of Veterans who are predominantly male, older in age, have a higher prevalence of CKD compared to the general population, and often have significant co-morbidities associated with CKD, such as diabetes mellitus, hypertension, vascular disease, and cancer[ 26 ].…”