Background: The evidence in the medical literature on the treatment of hepatitis C virus–associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. Aims: We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus–associated glomerular disease. Methods: In the first phase of the study, patients with hepatitis C virus–associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). Results: We enrolled 25 consecutive patients with hepatitis C virus–associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers (n = 2) and nonresponders (n = 3) with some benefit. Among patients on interferon-based regimens (n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers (n = 3) were successfully managed with immunosuppressive agents in two patients. Conclusion: Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus–related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.

Immunosuppressive and antiviral treatment of hepatitis C virus–associated glomerular disease : a long-term follow-up / F. Fabrizi, A. Aghemo, P. Lampertico, M. Fraquelli, D. Cresseri, G. Moroni, P. Passerini, F.M. Donato, P. Messa. - In: INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS. - ISSN 0391-3988. - 41:6(2018 Jun), pp. 306-318. [10.1177/0391398818762358]

Immunosuppressive and antiviral treatment of hepatitis C virus–associated glomerular disease : a long-term follow-up

P. Lampertico;P. Messa
2018

Abstract

Background: The evidence in the medical literature on the treatment of hepatitis C virus–associated glomerular disease is extremely limited. The advent of nonconventional immunosuppressive agents and direct-acting antivirals promises high efficacy and safety. Aims: We conducted an open-label, single-arm clinical study to examine the efficacy and safety of a combined approach for hepatitis C virus–associated glomerular disease. Methods: In the first phase of the study, patients with hepatitis C virus–associated glomerular disease received interferon-based antiviral therapy and immunosuppressive agents; since 2013, interferon-free antiviral therapy was adopted and novel immunosuppressants (including B-cell depleting agents and mycophenolate mofetil) or immunomodulators (ribavirin) were choiced. Virological and clinical responses were evaluated over a long observation period (median follow-up of 60 weeks and 46.5 months after the end of treatment with interferon and direct-acting antiviral agents, respectively). Results: We enrolled 25 consecutive patients with hepatitis C virus–associated glomerular disease, 8 being liver transplant recipients for hepatitis C. A total of 13 patients received therapy with direct-acting antivirals and experienced sustained viral response (serum hepatitis C virus RNA <12 IU/mL, 12 weeks after treatment ended, sustained viral response12). The mean (±standard deviation) proteinuria decreased from 2.61 ± 1.01 at baseline to 1.71 ± 1.43 (g/day) at sustained viral response 48, p = 0.031; microscopic hematuria and serum cryoglobulins disappeared in six (50%) and seven (64%) patients, respectively, after sustained viral response by direct-acting antivirals. Adverse events occurred in 69% (9/13) of patients and were mild, with four cases of ribavirin-related anemia requiring blood transfusions (no drop-outs). After sustained viral response by direct-acting antivirals, immunosuppressive and immunomodulatory agents were initiated in clinical relapsers (n = 2) and nonresponders (n = 3) with some benefit. Among patients on interferon-based regimens (n = 12), viral response (sustained viral response 24) and dropout rates were 58% (7/12) and 33% (4/12), respectively. After sustained viral response by interferon-based therapy, clinical relapsers (n = 3) were successfully managed with immunosuppressive agents in two patients. Conclusion: Treatment with direct-acting antivirals provides excellent rates of viral response and safety in patients with hepatitis C virus–related glomerular disease; viral response was frequently accompanied by clinical improvement. The absence of hepatitis C virus RNA from serum allowed immunosuppressive and immunomodulatory therapies with benefits for glomerular abnormalities and no concern on hepatitis C virus replication.
Antiviral agents; cryoglobulinemia; glomerulonephritis; hepatitis C; immunosuppression; Bioengineering; Medicine (miscellaneous); Biomaterials; Biomedical Engineering
Settore MED/12 - Gastroenterologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/580293
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