Incidence and Characteristics of de novo Renal Cryoglobulinemia After Direct-Acting Antivirals Treatment in an Egyptian Hepatitis C Cohort

Abstract

Introduction: The side effects profile of the new direct-­acting antivirals for the treatment of hepatitis C virus (HCV) is not fully elucidated. Objective: In this cross-sectional study, we aim to describe the incidence and characteristics of a novel observation of de novo renal cryoglobulinemic glomerulonephritis after successful treatment with DAA. Methodology: A total of 12,985 Hepatitis C Patients (genotype IV) received the new DAA. After successful treatment, patients with deranged renal functions or proteinuria were referred to the nephrology department for assessment. The clinical manifestations ranged from lower limb edema to the development of purpura skin lesions. Cryoglobulins were tested in the serum using the PCR detection. Results: Fifty patients had detectable de novo cryoglobulins in the serum. The most common type in renal biopsies was membranoproliferative glomerulonephritis (52%) and chronic kidney disease (CKD) developed in 46% of cases. Conclusion: De novo cryoglobulinemic glomerulonephritis and progression to CKD may rarely complicate successful treatment of HCV using direct-acting antivirals.

Persistence of Cryoglobulinemic Vasculitis after DAA Induced HCV Cure

“…Two thousand articles were initially identified through database-searching on PubMed, Embase, Cochrane, Web of Science, and clinicaltrials.gov. Ultimately, 19 studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] meeting the prespecified inclusion criteria were selected (Figure 2).…”

“…Clinical relapse was reported when there was a recurrence of purpura, arthralgia/arthritis, neuropathy, or nephropathy after CR or PR. Serological relapses were defined by cryoglobulins >1.5%, elevated rheumatoid factor (RF), or detectable complement 4 (C4) after the in- Out of the 19 included studies, the CryoVas response and relapse rates were provided in 14 studies and are summarized in Table 1 [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. It includes data from 11 prospective cohort studies, 2 retrospective cohort studies, and 1 cross-sectional study.…”

“…In a cross-sectional Egyptian study by Fayed et al [21], a total of 12,985 patients with genotype 4 chronic hepatitis C received DAA. All patients had a normal renal function and no signs of immune activation before therapy (normal C4, Negative rheumatoid factor, Negative serum cryoglobulin).…”

Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney Disease

“…However, given that multiple studies have shown the DAAs are efficacious in patients with CGN (29,30), it is now recommended per KDIGO guidelines that DAAs be used as first line treatment for cryoglobulinemic glomerulonephritis and that immunosuppression with rituximab-based therapy be reserved for patients with severe manifestations of vasculitis (rapidly-progressive glomerulonephritis, pulmonary hemorrhage) or those with persistent glomerulonephritis after completing DAAs (31). It is important to note that de novo cryoglobulinemic glomerulonephritis can occur after cure of HCV with DAAs, though the incidence is rare (32). In this instance, rituximab-based immunosuppression treatment should be used.…”

“…A summary of "real-world" use of DAAs in kidney transplant recipient confirmed high cure rates (97%) and low acute rejection rates (3%) (50). HCV-related post-transplant glomerulonephritis is likely to be less common in transplant recipients who have received DAAs, however it is important to note that de novo cryoglobulinemic glomerulonephritis has been described in HCV-infected patients who have been cured of HCV (32).…”