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Covic A, Caruntu ID, Burlacu A, Giusca SE, Covic A, Stefan AE, Brinza C, Ismail G. Therapeutic Potential of Rituximab in Managing Hepatitis C-Associated Cryoglobulinemic Vasculitis: A Systematic Review. J Clin Med 2023; 12:6806. [PMID: 37959271 PMCID: PMC10648453 DOI: 10.3390/jcm12216806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 10/18/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
(1) Background. Hepatitis C infection often leads to extrahepatic manifestations, including cryoglobulinemic vasculitis. This systematic review aimed to assess the efficacy and safety of rituximab in treating hepatitis C-associated cryoglobulinemic vasculitis. (2) Methods. Following PRISMA guidelines, databases were searched for relevant studies. Eligibility criteria included studies on hepatitis C-associated cryoglobulinemic vasculitis treated with rituximab. (3) Results. Nine studies met the eligibility criteria and were included in this analysis. Rituximab was commonly administered at 375 mg/m2 weekly for one month. The results consistently demonstrated the efficacy of rituximab, whether as a standalone treatment or as part of a therapeutic regimen. The combination of rituximab with Peg-IFN-α and ribavirin significantly increased the complete response rate compared to Peg-IFN-α and ribavirin alone (54.5% vs. 33.3%, p < 0.05). The 3-year sustained response rate was notably higher in the rituximab combination group (83.3% vs. 40%). In another trial, rituximab achieved remission in 83.3% of patients at 6 months, compared to only 8.3% in the control group. The efficacy of rituximab was supported by long-term experience, with clinical benefits in patients with severe cryoglobulinemic vasculitis, including those resistant to standard therapies. Mild adverse events were generally reported, with rare severe reactions in some studies. (4) Conclusions: In conclusion, rituximab appeared to be effective and safe in managing hepatitis C-associated cryoglobulinemic vasculitis, either alone or with antiviral therapy.
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Affiliation(s)
- Andreea Covic
- Nephrology Department, Dialysis and Renal Transplant Center, “Dr. C.I. Parhon” University Hospital, 700503 Iasi, Romania; (A.C.); (A.C.); (A.E.S.)
- Faculty of Medicine, ‘Grigore T. Popa’ University of Medicine, 700115 Iasi, Romania; (I.D.C.); (A.B.); (C.B.)
| | - Irina Draga Caruntu
- Faculty of Medicine, ‘Grigore T. Popa’ University of Medicine, 700115 Iasi, Romania; (I.D.C.); (A.B.); (C.B.)
- Department of Morpho-Functional Sciences I—Histology, Pathology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Alexandru Burlacu
- Faculty of Medicine, ‘Grigore T. Popa’ University of Medicine, 700115 Iasi, Romania; (I.D.C.); (A.B.); (C.B.)
- Department of Interventional Cardiology, Cardiovascular Diseases Institute “Prof. Dr. George I.M. Georgescu”, 700503 Iasi, Romania
| | - Simona Eliza Giusca
- Faculty of Medicine, ‘Grigore T. Popa’ University of Medicine, 700115 Iasi, Romania; (I.D.C.); (A.B.); (C.B.)
- Department of Morpho-Functional Sciences I—Histology, Pathology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Adrian Covic
- Nephrology Department, Dialysis and Renal Transplant Center, “Dr. C.I. Parhon” University Hospital, 700503 Iasi, Romania; (A.C.); (A.C.); (A.E.S.)
- Faculty of Medicine, ‘Grigore T. Popa’ University of Medicine, 700115 Iasi, Romania; (I.D.C.); (A.B.); (C.B.)
| | - Anca Elena Stefan
- Nephrology Department, Dialysis and Renal Transplant Center, “Dr. C.I. Parhon” University Hospital, 700503 Iasi, Romania; (A.C.); (A.C.); (A.E.S.)
| | - Crischentian Brinza
- Faculty of Medicine, ‘Grigore T. Popa’ University of Medicine, 700115 Iasi, Romania; (I.D.C.); (A.B.); (C.B.)
- Department of Interventional Cardiology, Cardiovascular Diseases Institute “Prof. Dr. George I.M. Georgescu”, 700503 Iasi, Romania
| | - Gener Ismail
- Department of Nephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania
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Sharma P, Sawtell R, Wang Q, Sise ME. Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:343-355. [PMID: 37657881 PMCID: PMC10479952 DOI: 10.1053/j.akdh.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 09/03/2023]
Abstract
Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.
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Affiliation(s)
- Purva Sharma
- Department of Medicine, Division of Nephrology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Glomerular Disease Center at Northwell Health, Hempstead, NY
| | - Rani Sawtell
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Qiyu Wang
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
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Younger DS. Adult and childhood vasculitis. HANDBOOK OF CLINICAL NEUROLOGY 2023; 195:653-705. [PMID: 37562892 DOI: 10.1016/b978-0-323-98818-6.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system leads to pervasive injury and disability, making this a disorder of paramount importance to all clinicians. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary CNS and PNS vasculitides, predicated on achievement in primary systemic forms. Primary neurological vasculitides can be diagnosed with assurance after intensive evaluation that incudes tissue confirmation whenever possible. Clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, unfortunately without the benefit of RCTs, and tempered by the recognition of anticipated medication side effects. It may be said that efforts to define a disease are attempts to understand the very concept of the disease. This has been especially evident in systemic and neurological disorders associated with vasculitis. For the past 100 years, since the first description of granulomatous angiitis of the brain, the CNS vasculitides have captured the attention of generations of clinical investigators around the globe to reach a better understanding of vasculitides involving the central and peripheral nervous system. Since that time it has become increasingly evident that this will necessitate an international collaborative effort.
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Affiliation(s)
- David S Younger
- Department of Clinical Medicine and Neuroscience, CUNY School of Medicine, New York, NY, United States; Department of Medicine, Section of Internal Medicine and Neurology, White Plains Hospital, White Plains, NY, United States.
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Quartuccio L, Bortoluzzi A, Scirè CA, Marangoni A, Del Frate G, Treppo E, Castelnovo L, Saccardo F, Zani R, Candela M, Fraticelli P, Mazzaro C, Renoldi P, Scaini P, Filippini DA, Visentini M, Scarpato S, Giuggioli D, Mascia MT, Sebastiani M, Zignego AL, Lauletta G, Fiorilli M, Casato M, Ferri C, Pietrogrande M, Pioltelli PE, De Vita S, Monti G, Galli M. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol 2023; 42:359-370. [PMID: 36169798 PMCID: PMC9873783 DOI: 10.1007/s10067-022-06391-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/06/2022] [Accepted: 09/21/2022] [Indexed: 01/28/2023]
Abstract
Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.
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Affiliation(s)
- Luca Quartuccio
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy.
| | - Alessandra Bortoluzzi
- Section of Rheumatology, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera, Universitaria Di Ferrara, Cona, FE, Italy
| | | | - Antonio Marangoni
- Section of Rheumatology, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera, Universitaria Di Ferrara, Cona, FE, Italy
| | - Giulia Del Frate
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy
| | - Elena Treppo
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy
| | - Laura Castelnovo
- Department of Internal Medicine, Hospital of Legnano, Legnano, Italy
| | | | | | | | - Paolo Fraticelli
- Ematologia Ed Immunologia Clinica, Clinica Medica Generale, University of Ancona, Ancona, Italy
| | - Cesare Mazzaro
- Clinical Experimental Onco-Haematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081, Aviano, Italy
| | - Piero Renoldi
- UOS Di Immunologia Clinica, Ospedale S. Carlo Borromeo, Milan, Italy
| | | | | | - Marcella Visentini
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Dilia Giuggioli
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Maria Teresa Mascia
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Marco Sebastiani
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | | | | | - Massimo Fiorilli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Milvia Casato
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Clodoveo Ferri
- Department of Internal Medicine, Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Maurizio Pietrogrande
- Department of Medicine, Surgery and Dentistry, Medicina Interna, Policlinico San Marco of Zingonia, University of Milan, Milan, Italy
| | | | - Salvatore De Vita
- Unit of Rheumatology, Department of Medicine (DAME), University of Udine, ASUFC, Udine, Italy
| | - Giuseppe Monti
- Medicina Interna, Ospedale Di Saronno, AO Busto Arsizio, Italy
| | - Massimo Galli
- Infectious Disease Unit, L. Sacco, Department of Clinical Sciences, University of Milan, Milan, Italy
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Fenoglio R, Sciascia S, Rossi D, Naretto C, Alpa M, Roccatello D. Non HCV-Related Mixed Cryoglobulinemic Vasculitis With Biopsy-Proven Renal Involvement: The Effects of Rituximab. Front Med (Lausanne) 2022; 9:819320. [PMID: 35419372 PMCID: PMC8995745 DOI: 10.3389/fmed.2022.819320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 03/03/2022] [Indexed: 11/17/2022] Open
Abstract
In the countries where HCV infection is still endemic, about 90% of subjects with mixed cryoglobulinemia had previously been infected with HCV and about 80% are RNA positive. Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking. This paper reports on a prospective single-Center open study aimed at evaluating the clinical presentation and effects of Rituximab administered alone in patients with severe non HCV-related cryoglobulinemic syndrome. The study group included 11 patients followed for at least 6 months. Three patients had type I cryoglobulinemia, 6 had type II and the remaining 2 patients had type III. Mean cryocrit was 2.5%. Four out of 11 patients had symptomatic sicca complex with anti-SSA (Ro)/anti SSB (La) antibodies. All 11 patients presented with biopsy-proven renal involvement, 4 out of 11 with leukocytoclastic vasculitis, and 8 with involvement of the peripheral nervous system. Renal biopsy revealed diffuse membranoproliferative glomerulonephritis (MPGN) in 9 out of 11 patients. Extracapillary proliferation and necrosis of the glomerular tuft was observed in 1 of these 9 cases. Interstitial nephritis together with mesangial expansion and capillary immune deposits were observed in 1 patient. Prevalent interstitial fibrosis and glomerular sclerosis were detected in the remaining case. Patients underwent treatment with rituximab alone. After 6 months we observed a remarkable improvement in the necrotizing skin ulcers and a substantial amelioration of the electrophysiological parameters of motor and sensory peripheral neuropathy. Improvement in both renal function (from 2.8 to 1.4 mg/dl, p < 0.001) and proteinuria (from 4.2 g/24 to 0.4 g/24 h, p < 0.001) was found in 10 out of 11 patients, while 1 could not be fully treated because of a severe infusion reaction and sudden development of anti-Rituximab antibodies. Good renal response was confirmed at the end of follow-up (38.4 months). Three patients had a relapse at 6, 12, and 48 months, respectively. In our cohort the administration of 4 once-weekly infusions of Rituximab followed by 2 more infusions after 1 and 2 months proved to be effective in the management of these rare patients.
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Affiliation(s)
- Roberta Fenoglio
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Savino Sciascia
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Daniela Rossi
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Carla Naretto
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Mirella Alpa
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
| | - Dario Roccatello
- Nephrology and Dialysis Unit (The European Rare Kidney Disease Reference Network, The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, and the European Reference Network That Aims at Improving the Care of Patients With Rare Immunological Disorders), Center of Research of Immunopathology and Rare Diseases- Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hub Hospital, Turin, Italy
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Cutaneous manifestations of monoclonal gammopathy. Blood Cancer J 2022; 12:58. [PMID: 35411042 PMCID: PMC9001632 DOI: 10.1038/s41408-022-00661-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/17/2022] [Accepted: 02/23/2022] [Indexed: 12/29/2022] Open
Abstract
Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and proliferation of a malignant plasma cells or by a deposition of the monoclonal immunoglobulin in a nonmalignant monoclonal gammopathy. These disorders include POEMS syndrome, light chain amyloidosis, Schnitzler syndrome, scleromyxedema and TEMPI syndrome. This article provides a review of clinical manifestations, diagnostics criteria, natural evolution, pathogenesis, and treatment of these cutaneous manifestations.
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Patel AM, Liu YS, Davies SP, Brown RM, Kelly DA, Scheel-Toellner D, Reynolds GM, Stamataki Z. The Role of B Cells in Adult and Paediatric Liver Injury. Front Immunol 2021; 12:729143. [PMID: 34630404 PMCID: PMC8495195 DOI: 10.3389/fimmu.2021.729143] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/16/2021] [Indexed: 12/16/2022] Open
Abstract
B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin. In this review we bring together information on liver B cell biology from different liver diseases, including alcohol-related and metabolic fatty liver disease, autoimmune hepatitis, primary biliary and primary sclerosing cholangitis, viral hepatitis and, in infants, biliary atresia. We also discuss the impact of B cell depletion therapy in the liver setting. Taken together, our analysis shows that B cells are important in the pathogenesis of liver diseases and that further research is necessary to fully characterise the human liver B cell compartment.
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Affiliation(s)
- Arzoo M. Patel
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Yuxin S. Liu
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Scott P. Davies
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Rachel M. Brown
- Department of Histopathology, Queen Elizabeth Hospital, Birmingham Women’s and Children’s National Health Service (NHS) Foundation Trust, Birmingham, United Kingdom
| | - Deirdre A. Kelly
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Dagmar Scheel-Toellner
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Gary M. Reynolds
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- The Liver Unit, Birmingham Women’s and Children’s Hospital and the University of Birmingham, Birmingham, United Kingdom
| | - Zania Stamataki
- Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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Tang X, Wan F, Yu J, Li X, Yang R, Zhu B. Clinicopathological characteristics of patients with paraproteinemia and renal damage. Eur J Med Res 2021; 26:68. [PMID: 34217367 PMCID: PMC8255003 DOI: 10.1186/s40001-021-00538-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 06/22/2021] [Indexed: 12/26/2022] Open
Abstract
Background This study aimed to analyze the clinicopathological characteristics of patients with paraproteinemia and renal damage. Methods Ninety-six patients from 2014 to 2018 with paraproteinemia and renal damage were enrolled and the clinical data, renal pathology, treatment and prognosis data were collected. Results A total of 96 patients (54 male and 42 female), accounting for 2.7% of all renal biopsies, were enrolled in this study. Among them, 42 were monoclonal gammopathy of renal significance (MGRS), 21 were renal monotypic immunoglobulin alone (renal monoIg), and 19 were monoclonal gammopathy of undetermined significance (MGUS). Individuals with multiple myeloma (MM) accounted for the fewest number of patients (n = 14). In the MGRS group, the main diseases were amyloidosis (n = 25) and cryoglobulinemic glomerulonephritis (n = 7), while in the MM group, the main diseases were cast nephropathy (n = 9) and light chain deposit disease (n = 3). In the MGUS group, it was mainly IgA nephropathy (IgAN, n = 10) and idiopathic membranous nephropathy (n = 5); while in the renal monoIg group, most of the cases were IgAN (n = 19). Chemotherapy was mainly administered to patients in the MM group, while immunosuppression therapy was mostly administered to patients in the renal monoIg group. Most patients with renal monoIg exhibited a major response, followed by the patients with MGUS and MGRS, while most of the patients with MM had a partial response but none had a major response. Approximately more than half (57.1%) of the patients with MM progressed to end-stage renal disease (ESRD), followed by MGRS (33.3%); however, the mortality rate was low in both the MGRS and MM groups. The survival analysis reviewed that serum creatinine, hemoglobin levels, and the serum κ/λ ratio were independent risk factors for ESRD in patients with MGRS. Conclusions The clinicopathological changes in patients with MGRS were between those in patients with MM and MGUS. The treatment for MGRS and MM was more intensive, and the overall mortality rate was low. Both MGUS and renal monoIg alone exhibited slighter clinicopathological features than MGRS and MM, and the treatment was focused mostly on primary renal diseases.
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Affiliation(s)
- Xuanli Tang
- Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China.
| | - Feng Wan
- Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Jin Yu
- Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Xiaohong Li
- Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Ruchun Yang
- Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
| | - Bin Zhu
- Department of Nephrology, Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China
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Mazzaro C, Dal Maso L, Gragnani L, Visentini M, Saccardo F, Filippini D, Andreone P, Zignego AL, Gattei V, Monti G, Galli M, Quartuccio L. Hepatitis B Virus-Related Cryoglobulinemic Vasculitis: Review of the Literature and Long-Term Follow-Up Analysis of 18 Patients Treated with Nucleos(t)ide Analogues from the Italian Study Group of Cryoglobulinemia (GISC). Viruses 2021; 13:1032. [PMID: 34070832 PMCID: PMC8226459 DOI: 10.3390/v13061032] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 05/05/2021] [Accepted: 05/26/2021] [Indexed: 01/05/2023] Open
Abstract
Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90-100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.
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Affiliation(s)
- Cesare Mazzaro
- Clinical Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO) IRCCS, 33081 Aviano, Italy;
| | - Luigino Dal Maso
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico (CRO) IRCCS, 33081 Aviano, Italy;
| | - Laura Gragnani
- MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, 50121 Firenze, Italy; (L.G.); (A.L.Z.)
| | - Marcella Visentini
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Francesco Saccardo
- Rheumatology Unit, Internal Medicine Unit, Presidio Ospedaliero di Saronno, ASST della Valle Olona, 21047 Saronno, Italy; (F.S.); (G.M.)
| | - Davide Filippini
- Rheumatology Unit, ASST Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy;
| | - Pietro Andreone
- Division of Internal Medicine, Department of Medical and Surgical Sciences, Maternal-Infantile and Adult, University of Modena and Reggio Emilia, 41124 Modena, Italy;
| | - Anna Linda Zignego
- MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Center for Research and Innovation CRIA-MASVE, 50121 Firenze, Italy; (L.G.); (A.L.Z.)
| | - Valter Gattei
- Clinical Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO) IRCCS, 33081 Aviano, Italy;
| | - Giuseppe Monti
- Rheumatology Unit, Internal Medicine Unit, Presidio Ospedaliero di Saronno, ASST della Valle Olona, 21047 Saronno, Italy; (F.S.); (G.M.)
| | - Massimo Galli
- Infectious Diseases, L. Sacco Hospital, Department of Biochemical and Clinical Sciences, University of Milan, 20157 Milan, Italy;
| | - Luca Quartuccio
- Rheumatology Clinic, Department of Medicine (DAME), ASUFC, University of Udine, 33100 Udine, Italy
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10
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Rossi D, Sciascia S, Fenoglio R, Ferro M, Baldovino S, Kamgaing J, Ventrella F, Kalikatzaros I, Viziello L, Solfietti L, Barreca A, Roccatello D. Cryoglobulinemic glomerulonephritis: clinical presentation and histological features, diagnostic pitfalls and controversies in the management. State of the art and the experience on a large monocentric cohort treated with B cell depletion therapy. Minerva Med 2020; 112:162-174. [PMID: 33198442 DOI: 10.23736/s0026-4806.20.07076-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cryoglobulinemia is defined by the presence of immunoglobulins having the following characteristics: forming a gel when temperature is <37 °C, precipitate in a reversible manner in the serum, and redissolve after rewarming. The presence of both polyclonal IgG and monoclonal IgM (type II), or of polyclonal IgG and polyclonal IgM (type III) identifies the mixed cryoglobulinemia (MC). The identification of the Hepatitis C virus (HCV) infection in most of the cases previously defined as "essential" represented a cornerstone in the understanding the pathogenesis of this condition. The picture of MC comprehends heterogeneous clinical presentations: from arthralgias, mild palpable purpura, fatigue to severe vasculitis features with skin necrotic pattern, peripheral neuropathy and, less commonly, lungs, central nervous system, gastrointestinal tract, and heart involvement. The kidney represents the most common organ presentation, and the presence of glomerulonephritis is a key element when considering prognosis. We discuss the clinical presentation and histological features, diagnostic pitfalls, and controversies in the management of patients with cryoglobulinemic glomerulonephritis, with a special focus on reporting our experience in treating patients with B cell depletion therapy.
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Affiliation(s)
- Daniela Rossi
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Savino Sciascia
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Roberta Fenoglio
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Michela Ferro
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Simone Baldovino
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Joelle Kamgaing
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Federica Ventrella
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Ileana Kalikatzaros
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Lucia Viziello
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Laura Solfietti
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy
| | - Antonella Barreca
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy.,Patology Division, A.O.U. Città della Salute e della Scienza, Turin, Italy
| | - Dario Roccatello
- Unit of Nephrology and Dialysis (ERKnet Member), Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital, University of Turin, Turin, Italy -
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11
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Mazzaro C, Mauro E, Ermacora A, Doretto P, Fumagalli S, Tonizzo M, Toffolutti F, Gattei V. Hepatitis C virus-related cryoglobulinemic vasculitis. Minerva Med 2020; 112:175-187. [PMID: 33198444 DOI: 10.23736/s0026-4806.20.07120-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection affects about 170 million people worldwide. HCV is responsible for both hepatitis and extra-hepatic manifestations. Chronic infection has been shown to develop in about 70% of cases, and it can progress to cirrhosis or hepatocellular carcinoma. Ten percent of HCV patients may develop extra-hepatic manifestations, including mixed cryoglobulinemia (MC) and non-Hodgkin lymphomas (NHL). Cryoglobulinemic vasculitis (CV) varies, ranging from mild-moderate clinical symptoms (purpura on the legs, asthenia and arthralgias) and chronic hepatitis to severe symptoms (ulcers on the legs, peripheral neuropathy, glomerulonephritis, low-grade NHL to life threatening complications (rapid progressive glomerulonephritis, gastrointestinal vasculitis, acute hyper-viscosity). EVIDENCE ACQUISITION CV is associated with significant morbidity and mortality. Some studies have shown kidney involvement, cirrhosis, central nervous system involvement, and heart involvement as unfavorable prognostic factors. Many studies have demonstrated that, after antiviral therapy, CV can disappear along with HCV. After the introduction of the new direct antiviral agents (DAAs), the combination of pegylated interferon and ribavirin has been abandoned. EVIDENCE SYNTHESIS Several studies on new DAAs have reported remarkable 90% to 100% HCV eradication rates, regardless of genotype. Treatment with DAAs has comparable efficacy on viral eradication in CV patients but definite clinical improvements of vasculitis can be observed only in half the patients. CONCLUSIONS In patients with mild to moderate CV disease, DAAs therapy should be used as first line approach. In patients with severe vasculitis, DAAs therapy and a second-line treatment with RTX with or without aphaeresis are a required.
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Affiliation(s)
- Cesare Mazzaro
- Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy -
| | - Endri Mauro
- Unit of Hematology, Department of Internal Medicine, Cà Foncello Hospital, Treviso, Italy
| | - Anna Ermacora
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Paolo Doretto
- Unit of Laboratory, Pordenone General Hospital, Pordenone, Italy
| | - Silvia Fumagalli
- Unit of Hematology, Department of Internal Medicine, Cà Foncello Hospital, Treviso, Italy
| | - Maurizio Tonizzo
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Federica Toffolutti
- Unit of Cancer Epidemiology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico (CRO), Aviano, Pordenone, Italy
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12
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Mazzaro C, Dal Maso L, Visentini M, Ermacora A, Tonizzo M, Gattei V, Andreone P. Recent news in the treatment of hepatitis B virus-related cryogobulinemic vasculitis. Minerva Med 2020; 111:566-572. [PMID: 32573522 DOI: 10.23736/s0026-4806.20.06771-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Hepatitis B virus (HBV) is a hepatotropic virus that causes hepatitis, cirrhosis and hepatocellular carcinoma. Twenty percent of HBV patients may develop extra-hepatic manifestations, such as polyarthritis nodosa, glomerulonephritis, dermatitis, poly-arthralgia and arthritis, and aplastic anemia. The association of HBV and cryoglobulinemic vasculitis (CV) has been highlighted by several epidemiological investigations. CV can develop in 0.5-4% of HBV infected patients. It has been demonstrated that suppression of HBV replication by nucleot(s)ide analogues (NAs) effectively induces clinical response in most patients with mild to moderate CV, but low responses are seen in severe CV. Based on this evidence, NAs therapy represents the first line therapeutic option in subjects with mild or moderate HBV related CV. Peg-interferon-Alfa can be an alternative treatment for HBV related CV, but the few studies published so far have shown no encouraging results. In patients with severe vasculitis and/or skin ulcers, peripheral neuropathy and glomerulonephritis treatment with rituximab (RTX) and NAs should be considered as a first line treatment. The long-term administration of low-medium glucocorticoid doses has been widely used in few studies to control clinical symptoms, but it should be used as a second option, when RTX is ineffective or not tolerated and in association with NAs. This review focuses on novel treatments for HBV related CV.
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Affiliation(s)
- Cesare Mazzaro
- Unit of Clinical Experimental Onco-Hematology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy -
| | - Luigino Dal Maso
- Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Marcella Visentini
- Depatment of Clinical Medicine, Laboratory affiliated to Pasteur Italia Institute - Cenci Bolognetti Foundation, Sapienza University, Rome, Italy
| | - Anna Ermacora
- Department of Internal Medicine, Hospital of Pordenone, Pordenone, Italy
| | - Maurizio Tonizzo
- Department of Internal Medicine, Hospital of Pordenone, Pordenone, Italy
| | - Valter Gattei
- Unit of Clinical Experimental Onco-Hematology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Pordenone, Italy
| | - Pietro Andreone
- SMECHIMAI Department, University of Modena and Reggio Emilia, Modena, Italy.,Department of Internal and Metabolic Medicine, University Hospital of Modena, Modena, Italy
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13
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Abstract
PURPOSE OF REVIEW The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with direct-acting antiviral agents (DAAs). RECENT FINDINGS Hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients with mixed cryoglobulinemia syndrome. Clinical research has been focused on antiviral drugs and, more recently, on the new, highly potent DAAs. New DAAs assure sustained virologic response (SVR) rates greater than 90% with relief of mild-to-moderate symptoms. SUMMARY Mixed cryoglobulinemia may present with multiorgan vasculitis involving kidneys, joints, skin, and peripheral nerves. Data on DAAs efficacy in HCV-associated cryoglobulinemic vasculitis are disappointing possibly because of the inability of these drugs to suppress the immune-mediated process once it has been triggered. Immunosuppression has often been employed in the past as a first-line therapy in cryoglobulinemic vasculitis despite the potential risk of the infection exacerbation. However, more manageable Rituximab-based therapeutic approaches have been more recently used without increase of viral load. Rituximab substantially changed the outcome of HCV-associated cryoglobulinemic vasculitis by providing long-term remission. A combination schedule of DAAs and Rituximab may result in eradication of both cryoglobulinemic vasculitis and HCV infection.
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14
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Boleto G, Saadoun D, Cacoub P. Strategies to prevent persistent or relapsed mixed cryoglobulinemia. Expert Opin Orphan Drugs 2020. [DOI: 10.1080/21678707.2020.1767586] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Gonçalo Boleto
- Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l’Amylose, France
| | - David Saadoun
- Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l’Amylose, France
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Université, UPMC Univ Paris 06, UMR 7211, Paris, France
- Inserm, Umr_s 959, Paris, France
| | - Patrice Cacoub
- Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires et de l’Amylose, France
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Université, UPMC Univ Paris 06, UMR 7211, Paris, France
- Inserm, Umr_s 959, Paris, France
- Cnrs, FRE3632, Paris, France
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15
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Feng Y, Yang M, Wu H, Lu Q. The pathological role of B cells in systemic lupus erythematosus: From basic research to clinical. Autoimmunity 2019; 53:56-64. [PMID: 31876195 DOI: 10.1080/08916934.2019.1700232] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease that often occurs in females of child-bearing age. It involves multiple systems and severely threatens human life. One of the typical characteristics of SLE is the formation of immune complexes with autoantibodies produced by B cells that target various autoantigens, thus indicating the pivotal role of B cells in the pathogenesis of SLE. Increasing evidence has shown abnormal expression of B cells in the peripheral blood of SLE patients. Moreover, numerous studies have shown that B cells in SLE patients are abnormally activated, as well as aberrantly differentiated, and are involved in the inflammatory cytokine milieu, abnormal transcription factor activity, and signalling pathways. Several biological therapies targeting B cells, such as anti-CD20 antibodies, have been intensively studied in preclinical and clinical trials. However, the results have not met expectations. Therefore, new therapies targeting B cells are in great need. This review will summarize the latest progress in basic research on B cells to better understand the pathogenesis of SLE and will discuss the outcomes of B-cell-targeting treatments that provide potential therapeutic targets and strategies for SLE. Studies have clarified high levels of IL-21 in serum from SLE patients and animal models. IL-21 promotes B cell differentiation, which results in antibodies accumulation leads to SLE. Therefore, further studies on IL-21 will give new perspectives on SLE treatments. In addition, the application of drugs targeting plasma cell depletion in SLE patients may also achieve satisfied results in treatment.
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Affiliation(s)
- Yu Feng
- Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China
| | - Ming Yang
- Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China
| | - Haijing Wu
- Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China
| | - Qianjin Lu
- Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China
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16
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Recommendations for managing the manifestations of severe and life-threatening mixed cryoglobulinemia syndrome. Autoimmun Rev 2019; 18:778-785. [PMID: 31181326 DOI: 10.1016/j.autrev.2019.06.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Accepted: 02/22/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Some of the manifestations of mixed cryoglobulinemia syndrome (MCS) can be severe or life-threatening, and should be rapidly contained but, as the therapeutic approaches to such conditions are largely based on anecdotal data, a consensus conference was organised by the Italian Group for the Study of Cryoglobulinemia (GISC) with the aim of providing a set of recommendations based on an in-depth survey of the available data and expert opinion. METHODS The consensus panel, which included specialists working in different medical fields involved in the management of MCS patients, was first asked to divide the manifestations of MCS into severe or life-threatening conditions on the basis of their own experience, after which a complete literature review was carried out in accordance with the Cochrane guidelines for systematic reviews. RESULTS Therapeutic plasma exchange (TPE) was considered the elective first-line treatment in the case of life-threatening manifestations of MCS (LT-MCS) and patients with severe clinical symptoms (S-MCS) who fail to respond to (or who are ineligible for) other treatments. The data supporting the combined use of cyclophosphamide and TPE were considered limited and inconclusive. High-dose pulsed glucocorticoid (GCS) therapy can be considered the first-line treatment of severe MCS, generally in association with TPE. Rituximab (RTX)-based treatments should be considered in patients with skin ulcers, peripheral neuropathy or glomerulonephritis, and in patients with persistent LT-MCS after TPE. In patients with hepatitis C virus-related MCS with S-MCS, viral eradication should be attempted as soon as a patient's condition allows the use of direct-acting antivirals.
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17
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Rutledge SM, Chung RT, Sise ME. Treatment of hepatitis C virus infection in patients with mixed cryoglobulinemic syndrome and cryoglobulinemic glomerulonephritis. Hemodial Int 2019; 22 Suppl 1:S81-S96. [PMID: 29694729 DOI: 10.1111/hdi.12649] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cryoglobulinemia is a common extrahepatic manifestation of infection with hepatitis C virus (HCV). When signs and symptoms of systemic vasculitis or glomerulonephritis occur in the presence of circulating cryoglobulins, this syndrome is called "mixed cryoglobulinemia syndrome" (MCS). Historically, interferon-based therapies in HCV have been associated with lower rates of viral cure in patients with MCS than in the general HCV-infected population. The advent of direct-acting antiviral therapies have revolutionized the treatment of HCV, dramatically increasing rates of cure. Early studies of first-generation protease inhibitors (telaprevir and boceprevir) in combination with interferon and ribavirin demonstrated HCV cure rates of 67% and complete clinical response rates of vasculitis symptoms in 60% of patients with MCS; however, regimens were poorly tolerated by patients, 22% discontinued treatment early. More recently, all-oral, interferon-free regimens have become available and combination therapies are now being approved for patients with and without renal impairment. Patients with HCV-MCS achieved sustained virologic response in 297 out of 313 patients (95%) treated with direct-acting antiviral therapy, and 85% had a complete or partial clinical response of MCS symptoms. Current direct-acting antiviral therapies are well tolerated in patients with HCV-MCS and only 1.6% discontinued treatment early. Patients with cryoglobulinemic glomerulonephritis also had an excellent cure rate (94%). The majority improved; 17/52 (33%) experienced full remission and 15/52 (29%) experienced partial remission. There were no reports of worsening kidney function in patients treated with direct-acting antiviral therapies. Less than 5% of patients with HCV-MCS treated with IFN-free direct-acting antiviral therapy required immunosuppression. However, patients with severe vasculitis appear to still require concomitant immunosuppression.
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Affiliation(s)
- Stephanie M Rutledge
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Meghan E Sise
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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18
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Abstract
The diagnosis of primary central and peripheral nerve vasculitides should be established with certainty if suspected before commencing potent immunosuppressive therapy. The aim of induction therapy is to rapidly control the underlying inflammatory response and stabilize the blood-brain and blood-nerve barriers, followed by maintenance immunosuppression tailored to the likeliest humoral and cell-mediated autoimmune inflammatory vasculitic processes.
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Affiliation(s)
- David S Younger
- Department of Neurology, Division of Neuro-Epidemiology, New York University School of Medicine, New York, NY, USA; School of Public Health, City University of New York, New York, NY, USA.
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19
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Cacoub P, Comarmond C. Considering hepatitis C virus infection as a systemic disease. Semin Dial 2018; 32:99-107. [PMID: 30549107 DOI: 10.1111/sdi.12758] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus (HCV) infection has been demonstrated to result in several adverse hepatic outcomes and has been associated with a number of important extrahepatic manifestations. The scope of extrahepatic clinical possibilities includes systemic diseases such as vasculitis and lymphoproliferative disorders, cardiovascular disease, myalgia, arthritis, and sicca syndrome. These end-organ effects of HCV may dominate the clinical course beyond the hepatic complications and significantly worsen the long-term prognosis of infected patients. Until several years ago, the standard of care for the treatment of HCV infection had been interferon-alpha-based regimens, which not only had limited effectiveness in achieving a cure but were often poorly tolerated, especially in patients with kidney disease. In those HCV-infected patients with significant systemic manifestations, the interferon-based regimens were problematic given their association with a wide variety of toxicities. The development of highly effective direct-acting antiviral agents to treat HCV infection presented an opportunity to improve the HCV care cascade with the eradication of HCV in most infected patients and by reducing the burden of both hepatic and extrahepatic complications.
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Affiliation(s)
- Patrice Cacoub
- UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, Paris, France.,INSERM, UMR_S 959, Paris, France.,CNRS, FRE3632, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Cloé Comarmond
- UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, Paris, France.,INSERM, UMR_S 959, Paris, France.,CNRS, FRE3632, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
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20
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Younossi Z, Papatheodoridis G, Cacoub P, Negro F, Wedemeyer H, Henry L, Hatzakis A. The comprehensive outcomes of hepatitis C virus infection: A multi-faceted chronic disease. J Viral Hepat 2018; 25 Suppl 3:6-14. [PMID: 30398294 DOI: 10.1111/jvh.13005] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 08/16/2018] [Indexed: 02/06/2023]
Abstract
Treatment of hepatitis C virus (HCV) infection has been revolutionized with the introduction of pangenotypic, interferon- and ribavirin-free regimens associated with high cure rates and a low side effect profile. Additionally, there is evidence that HCV cure reduces HCV complications, improves patient-reported outcomes and is cost-saving in most western countries in the long term. This is a review of the comprehensive burden of HCV and the value of eliminating HCV infection. With the introduction of the interferon-free all-oral, once a day pill treatment regimen for the cure of HCV, the potential to eliminate HCV by 2030 has become a possibility for some regions of the world. Nevertheless, there are barriers to screening, linkage to care, and treatment in many countries that must be overcome in order to reach this goal. In conclusion, globally, work must continue to ensure national policies are in place to support screening, linkage to care and affordable treatment in order to eliminate HCV.
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Affiliation(s)
- Zobair Younossi
- Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia.,Beatty Center for Integrated Research, Inova Health System, Falls Church, Virginia
| | - Georgios Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens Laiko, Athens, Greece
| | - Patrice Cacoub
- Department of Internal Medicine and Clinical Immunology, AP HP Hôpital La Pitié-Salpêtrière, Paris, France.,CNRS UMR 7087, INSERM UMR S-959, DHU I2B, Sorbonne Université, Paris, France
| | | | | | - Linda Henry
- Center for Outcomes Research in Liver Disease, Washington D.C
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece.,Hepatitis B and C Public Policy Association, L-2453 , Luxembourg
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21
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Long JD, Rutledge SM, Sise ME. Autoimmune Kidney Diseases Associated with Chronic Viral Infections. Rheum Dis Clin North Am 2018; 44:675-698. [PMID: 30274630 DOI: 10.1016/j.rdc.2018.06.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Autoimmune kidney diseases triggered by viruses are an important cause of kidney disease in patients affected by chronic viral infection. Hepatitis B virus (HBV) infection is associated with membranous nephropathy and polyarteritis nodosa. Hepatitis C virus (HCV) infection is a major cause of cryoglobulinemic glomerulonephritis. Patients with human immunodeficiency virus (HIV) may develop HIV-associated nephropathy, a form of collapsing focal segmental glomerulosclerosis, or various forms of immune-complex-mediated kidney diseases. This article summarizes what is known about the pathogenesis, diagnosis, and management of immune-mediated kidney diseases in adults with chronic HBV, HCV, and HIV infections.
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Affiliation(s)
- Joshua D Long
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, 55 Fruit Street, GRB 7, Boston, MA 02114, USA
| | - Stephanie M Rutledge
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, 55 Fruit Street, GRB 7, Boston, MA 02114, USA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, 55 Fruit Street, GRB 7, Boston, MA 02114, USA.
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22
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Abstract
Cryoglobulinaemia refers to the serum presence of cryoglobulins, which are defined as immunoglobulins that precipitate at temperatures <37 °C. Type I cryoglobulinaemia consists of only one isotype or subclass of monoclonal immunoglobulin, whereas type II and type III are classified as mixed cryoglobulinaemia because they include immunoglobulin G (IgG) and IgM. Many lymphoproliferative, infectious and autoimmune disorders have been associated with mixed cryoglobulinaemia; however, hepatitis C virus (HCV) is the aetiologic agent in most patients. The underlying mechanism of the disorder is B cell lymphoproliferation and autoantibody production. Mixed cryoglobulinaemia can cause systemic vasculitis, with manifestations ranging from purpura, arthralgia and weakness to more serious lesions with skin ulcers, neurological and renal involvement. This Primer focuses on mixed cryoglobulinaemia, which has a variable course and a prognosis that is primarily influenced by vasculitis-associated multiorgan damage. In addition, the underlying associated disease in itself may cause considerable mortality and morbidity. Treatment of cryoglobulinaemic vasculitis should be modulated according to the underlying associated disease and the severity of organ involvement and relies on antiviral treatment (for HCV infection), immunosuppression and immunotherapy, particularly anti-CD20 B cell depletion therapies.
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23
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Roccatello D, Sciascia S, Rossi D, Solfietti L, Fenoglio R, Menegatti E, Baldovino S. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents. Oncotarget 2018; 8:41764-41777. [PMID: 28454112 PMCID: PMC5522247 DOI: 10.18632/oncotarget.16986] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2016] [Accepted: 03/09/2017] [Indexed: 12/30/2022] Open
Abstract
Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.
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Affiliation(s)
- Dario Roccatello
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy.,Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Savino Sciascia
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy.,Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Daniela Rossi
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Laura Solfietti
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Roberta Fenoglio
- Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Elisa Menegatti
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
| | - Simone Baldovino
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy
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24
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Cortés-Vicente E, Rojas-Garcia R, Díaz-Manera J, Querol L, Casasnovas C, Guerrero-Sola A, Muñoz-Blanco JL, Bárcena-Llona JE, Márquez-Infante C, Pardo J, Martínez-Fernández EM, Usón M, Oliva-Nacarino P, Sevilla T, Illa I. The impact of rituximab infusion protocol on the long-term outcome in anti-MuSK myasthenia gravis. Ann Clin Transl Neurol 2018; 5:710-716. [PMID: 29928654 PMCID: PMC5989782 DOI: 10.1002/acn3.564] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/07/2018] [Accepted: 03/20/2018] [Indexed: 01/11/2023] Open
Abstract
Objective To evaluate whether the clinical benefit and relapse rates in anti‐muscle‐specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. Methods This retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan–Meier methods and survival analyses were undertaken using Cox proportional‐hazards models. Results Twenty‐five patients were included: 11 treated with protocol 4 + 2 (375 mg/m2/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m2/4 weeks). Mean follow‐up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan–Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log‐rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7–2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9–91.8, P = 0.059). Interpretation This study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG.
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Affiliation(s)
- Elena Cortés-Vicente
- Neuromuscular Diseases Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain
| | - Ricard Rojas-Garcia
- Neuromuscular Diseases Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain
| | - Jordi Díaz-Manera
- Neuromuscular Diseases Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain
| | - Luis Querol
- Neuromuscular Diseases Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain
| | - Carlos Casasnovas
- Neuromuscular Diseases Unit Department of Neurology Hospital Universitari de Bellvitge - IDIBELL L'Hospitalet de Llobregat Barcelona Spain
| | - Antonio Guerrero-Sola
- Neuromuscular Diseases Unit Department of Neurology Hospital Universitario Clínico San Carlos Madrid Spain
| | - José Luis Muñoz-Blanco
- ALS-Neuromuscular Unit Department of Neurology Hospital General Universitario Gregorio Marañón IISGM Madrid Spain
| | | | - Celedonio Márquez-Infante
- Neuromuscular Diseases Unit Department of Neurology and Neurophysiology Hospital Universitario Virgen del Rocío Sevilla Spain
| | - Julio Pardo
- Department of Neurology Hospital Clínico Santiago de Compostela Spain
| | | | - Mercedes Usón
- Department of Neurology Hospital Son Llàtzer Palma de Mallorca Spain
| | | | - Teresa Sevilla
- Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain.,Neuromuscular Unit Department of Neurology Hospital Universitari i Politècnic La Fe Valencia Spain.,Department of Medicine University of Valencia Valencia Spain
| | - Isabel Illa
- Neuromuscular Diseases Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.,Centre for Biomedical Network Research on Rare Diseases (CIBERER) Madrid Spain
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25
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Fabrizi F, Bruchfeld A, Mangano S, Dixit V, Messa P, Martin P. Interferon Therapy for HCV-Associated Glomerulonephritis: Meta-Analysis of Controlled Trials. Int J Artif Organs 2018; 30:212-9. [PMID: 17417760 DOI: 10.1177/039139880703000306] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Background A relationship between hepatitis C virus (HCV) infection and chronic glomerulonephritis (GN) has been asserted on the grounds of epidemiological and experimental data. Although this suggests a role for an antiviral approach to HCV-associated GN instead of the more conventional immunosuppressive (or supportive) therapy, the optimal management of HCV-related glomerulonephritis remains controversial. Objective To compare antiviral with immunosuppressive therapy for HCV-associated GN. Design Meta-analysis of controlled clinical trials (CCTs) of the two treatments (antiviral versus immunosuppressive) of HCV-associated GN. Methods We used the fixed or random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. The rate of proteinuria and serum creatinine decrease after therapy for HCV-associated GN were regarded as the most reliable outcome end-points. Results We identified six studies involving 145 unique patients with HCV-associated GN. Pooling of study results demonstrated that proteinuria decreased more commonly after IFN than corticosteroid therapy (OR 1.92 (95% CI, 0.39; 9.57), NS), P-test for heterogeneity, 0.06 (I2=52.9%). In a sensitivity analysis including only CCTs using standard IFN-doses, OR was 3.86 (95% CI, 1.44; 10.33, (P=0.007)), P-test for heterogeneity, 0.18 (I2=35.9%). No improvement of serum creatinine after IFN compared to immunosuppressive therapy was noted (OR, 0.59 (95% CI, 0.21; 1.65), NS), P-test for heterogeneity, 0.76 (I2=0%). Only three CCTs gave information on the rate of proteinuria decrease over follow-up (OR, 5.08 (95% CI, 0.69; 37.31), NS). A few major side effects were noted after IFN administration. Conclusions Our meta-analysis indicates that standard IFN-doses were more effective than immunosuppressive therapy in lowering proteinuria of patients with HCV-related glomerulonephritis. However, no significant improvement in serum creatinine was seen by IFN or steroid therapy across the studies. Also, information on proteinuria recurrence after the completion of antiviral therapy was not sufficient. Prospective, randomized trials based on combined antiviral therapy (pegylated IFN plus ribavirin) with adequate dose and follow-up are required to assess the efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis.
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Affiliation(s)
- F Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS, Via Commenda 15, 20122 Milan, Italy.
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26
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Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev 2017; 16:523-541. [PMID: 28286108 DOI: 10.1016/j.autrev.2017.03.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 02/26/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.
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Affiliation(s)
- Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Dario Roccatello
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Klinik für Rheumatologie Oberarzt, Ratzeburger Allee 160 (Haus 40), 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room, 32 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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27
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Abstract
Cryoglobulinemia is a systemic inflammatory syndrome that generally involves small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes. The therapeutic management of idiopathic cryoglobulinemic vasculitis has yet to be defined because no study has evaluated the best strategies. However, treatment of severe vasculitis is traditionally based on a combination of corticosteroids and immunosuppressants or plasmapheresis, and more recently rituximab. We report a case of 77-year-old female patient diagnosed with idiopathic cryoglobulinemia, treated successfully with 6 months prednisone tapering and 2 doses of rituximab (1 g each dose). After receiving the above-mentioned treatment, her creatinine went back to normal with resolution of proteinuria and hematuria, normalization of serum complements, and significant improvement in her clinical picture. We conclude that rituximab could be an effective treatment for idiopathic cryoglobulnemia.
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28
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Ryu A, Shimamura Y, Hasegawa K, Moniwa N, Takizawa H, Kang JH, Sakai H, Ogawa Y. [Case Report; Hepatitis B virus-associated cryoglobulinemia with membranoproliferative glomerulonephritis]. ACTA ACUST UNITED AC 2016; 103:2807-9. [PMID: 27522822 DOI: 10.2169/naika.103.2807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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29
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Cacoub P, Comarmond C. New insights into HCV-related rheumatologic disorders: A review. J Adv Res 2016; 8:89-97. [PMID: 28149645 PMCID: PMC5272935 DOI: 10.1016/j.jare.2016.07.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 07/17/2016] [Accepted: 07/18/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infected patients are known to be exposed to major liver complications i.e. cirrhosis and hepatocellular carcinoma. In addition, many extrahepatic manifestations including rheumatologic disorders have been reported in up to two-third of HCV infected patients. These manifestations include frank auto-immune and rheumatic diseases (such as arthralgia, myalgia, arthritis, sicca syndrome and vasculitis) which may dominate the course of infection. Until recently, the standard of care of HCV has been the use of interferon-alpha based regimens, which not only had limited effectiveness in HCV cure but were poorly tolerated. In patients with rheumatic diseases interferon-based regimens may be problematic given their association with a wide variety of autoimmune toxicities. Recent therapeutic advances with new direct anti-HCV therapies (interferon-free) which are more effective and better tolerated, make screening for this comorbidity in patients with rheumatic disorders more important than ever. This review aimed to outline main HCV extrahepatic with a special focus on rheumatologic manifestations.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France
| | - Cloé Comarmond
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005 Paris, France; INSERM, UMR_S 959, F-75013 Paris, France; CNRS, FRE3632, F-75005 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, F-75013 Paris, France
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30
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Isnard Bagnis C, Cacoub P. Hepatitis C Therapy in Renal Patients: Who, How, When? Infect Dis Ther 2016; 5:313-27. [PMID: 27388502 PMCID: PMC5019972 DOI: 10.1007/s40121-016-0116-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Indexed: 02/07/2023] Open
Abstract
Renal patients are overexposed to hepatitis C virus (HCV) infection. Hepatitis C virus infection may induce renal disease, i.e., cryoglobulinemic membrano-proliferative glomerulopathy and non-cryoglobulinemic nephropathy. Hepatitis C virus impacts general outcomes in chronic kidney disease, dialysis or transplanted patients. Hepatitis C virus infection is now about to be only part of their medical history thanks to new direct acting antiviral drugs exhibiting as much as over 95% of sustained virological response. All HCV-infected patients potentially can receive the treatment. Control of the virus is associated with better outcomes in all cases, whatever the severity of the hepatic or renal disease. This article focuses on HCV-induced renal diseases, the reciprocal impact of HCV infection on the renal outcome and renal status in liver disease, use of new direct-acting antiviral drugs with dosage adaptations and the most recent safety data.
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Affiliation(s)
- Corinne Isnard Bagnis
- Department of Nephrology AP-HP, Groupe Hospitalier Pitié Salpêtrière, 75013, Paris, France. .,UPMC Univ Paris 06, Paris, France.
| | - Patrice Cacoub
- Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 75005, Paris, France.,INSERM, UMR_S 959, 75013, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.,Sorbonne University, UPMC Univ Paris 06, UMR 7211, Paris, France
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31
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Mazzaro C, Dal Maso L, Urraro T, Mauro E, Castelnovo L, Casarin P, Monti G, Gattei V, Zignego AL, Pozzato G. Hepatitis B virus related cryoglobulinemic vasculitis: A multicentre open label study from the Gruppo Italiano di Studio delle Crioglobulinemie - GISC. Dig Liver Dis 2016; 48:780-4. [PMID: 27106525 DOI: 10.1016/j.dld.2016.03.018] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Revised: 01/21/2016] [Accepted: 03/29/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Cryoglobulinemic vasculitis (CV) related to Hepatitis-B Virus (HBV) is rare and its treatment is ill-defined. AIMS To describe clinical and treatment characteristics of HBV-related CV patients. In addition, the efficacy of treatment with antiviral agent nucleotide (NUC), including Entecavir, Adefovir, and Lamivudine, was explored. METHODS In four Italian centres, 17 HBV-positive CV patients (median age 56 years, range 45-70) were enrolled. RESULTS The extrahepatic manifestations were: purpura (100%), arthralgias (71%), peripheral neuropathy (29%), chronic hepatitis (47%), liver cirrhosis (29%), and glomerulonephritis (18%). Mixed cryoglobulinemias were type II (88%) and type III (12%). The median cryocrit was 3% (range 1-14), rheumatoid factor was 200U/L (range 20-5850), C4 was 12mg/dl (range 2-31), ALT 71U/L (range 36-114). All patients were HBsAg-positive and 80% anti-HbeAg-positive. At enrollment, they were treated with steroids (eight), Entecavir (five), Alpha-IFN (two), Adefovir and Lamivudine (one each). After NUC treatment, no disease progression was observed and, in all patients, HBV-DNA became undetectable. Moreover, a regression of purpura and a reduction of cryocrit were observed. Four patients died during therapy, two of kidney failure and two of liver cirrhosis. CONCLUSION NUC therapy appeared to be safe and effective in CV-related HBV.
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Affiliation(s)
- Cesare Mazzaro
- Clinical and Experimental Onco-Hematology Unit, CRO Aviano National Cancer Institute, Aviano, Italy.
| | - Luigino Dal Maso
- Epidemiology and Biostatistics Unit, CRO-Aviano National Cancer Institute, Aviano, Italy.
| | - Teresa Urraro
- Centro Manifestazioni Sistemiche da Virus Epatitici, University of Florence, Firenze, Italy
| | - Endri Mauro
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Laura Castelnovo
- Department of Internal Medicine, Saronno General Hospital, Saronno (VA), Italy
| | - Pietro Casarin
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Giuseppe Monti
- Department of Internal Medicine, Saronno General Hospital, Saronno (VA), Italy
| | - Valter Gattei
- Clinical and Experimental Onco-Hematology Unit, CRO Aviano National Cancer Institute, Aviano, Italy
| | - Anna Linda Zignego
- Centro Manifestazioni Sistemiche da Virus Epatitici, University of Florence, Firenze, Italy
| | - Gabriele Pozzato
- Department of Medical and Surgical Sciences, University of Trieste, Trieste, Italy
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32
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Coughlan R, Cameron S. Key data from the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV. Antivir Ther 2016; 21:75-89. [PMID: 26857256 DOI: 10.3851/imp3031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2016] [Indexed: 10/22/2022]
Abstract
Combination antiretroviral therapy (cART) has significantly reduced HIV-related morbidity and mortality; however, residual inflammation often persists in the absence of detectable viral load. In addition, chronic use of cART and an ageing HIV-positive population present new challenges to treating physicians who must balance the need for good virological control with risk of treatment-related toxicities. Discussions at the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV once again sought a better understanding of the complex relationship between HIV-, treatment- and age-related factors in the development of comorbidities in those infected with HIV. Key data from the meeting pertaining to inflammatory pathways in HIV, adipose tissue metabolism, cardiovascular disease, bone health, ageing and frailty, neurocognitive dysfunction, pulmonary disease and HCV coinfection are the focus of this report.
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Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently present with extrahepatic manifestations covering a large spectrum, involving different organ systems leading to the concept of systemic HCV infection. These manifestations include autoimmune phenomena and frank autoimmune and/or rheumatic diseases and may dominate the course of chronic HCV infection. Chronic HCV infection causes liver inflammation affecting the development of hepatic diseases. HCV is also a lymphotropic virus that triggers B cells and promotes favorable conditions for B lymphocyte proliferation, including mixed cryoglobulinemia (MC) and MC vasculitis, which is the most prominent extrahepatic manifestation of chronic HCV infection. HCV may also promote a low-grade chronic systemic inflammation that may affect the development of some extrahepatic manifestations, particularly cardiovascular and cerebral vascular diseases. Recognition of extrahepatic symptoms of HCV infection could facilitate early diagnosis and treatment. The development of direct-acting antiviral agents (DDAs) has revolutionized HCV treatment. DDAs, as well as new B-cell-depleting or B-cell-modulating monoclonal antibodies, will expand the panorama of treatment options for HCV-related extrahepatic manifestations including cryoglobulinemic vasculitis. In this context, a proactive, integrated approach to HCV therapy should maximize the benefits of HCV therapy, even when liver disease is mild.
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Affiliation(s)
- E Rosenthal
- Service de Médecine Interne, Hôpital de l'Archet, CHU de Nice, Nice; Université de Nice-Sophia Antipolis, Nice, France COREVIH PACA EST, CHU de Nice, France
| | - P Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France INSERM, UMR_S 959, Paris, France CNRS, FRE3632, Paris, France AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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34
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Visentini M, Tinelli C, Colantuono S, Monti M, Ludovisi S, Gragnani L, Mitrevski M, Ranieri J, Fognani E, Piluso A, Granata M, De Silvestri A, Scotti V, Mondelli MU, Zignego AL, Fiorilli M, Casato M. Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: Phase II clinical trial and systematic review. Autoimmun Rev 2015; 14:889-96. [PMID: 26031898 DOI: 10.1016/j.autrev.2015.05.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Accepted: 05/24/2015] [Indexed: 01/11/2023]
Abstract
OBJECTIVE To evaluate whether rituximab at a low dose of 250 mg/m(2) × 2 may be as effective as at higher dosages, most commonly 375 mg/m(2)×4, used in previous studies on the treatment of patients with refractory mixed cryoglobulinemia (MC) vasculitis associated with hepatitis C virus (HCV) infection. METHODS We conducted a phase 2, single-arm two-stage trial (EUDRACT n. 2008-000086-38) of low-dose rituximab in 52 patients with HCV-associated MC who were ineligible/intolerant or non-responder to antiviral therapy. The primary outcomes were response of vasculitis evaluated by the Birmingham Vasculitis Activity Score (BVAS) at months 3, 6 and 12, rate of relapses and time to relapse, and rate of adverse events. Our data were compared with those reported in 19 published studies selected among 291 reviewed in a literature search. RESULTS The cumulative response rate (complete and partial) at month 3 was 81% in our patients, and 86% in 208 patients from studies using high-dose rituximab. The relapse rate and median time to relapse were, respectively, 41% and 6 months in our study, and 32% and 7 months in high-dose studies. Treatment-related adverse events were 11.5% in our study and 19.9% in high-dose studies. None of these differences was statistically significant. CONCLUSION Rituximab at a low dosage of 250 mg/m(2) × 2 is as effective as at higher dosages for treating MC vasculitis. This low-dose regimen may improve the cost/benefit profile of rituximab therapy for MC.
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Affiliation(s)
- Marcella Visentini
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
| | - Carmine Tinelli
- Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
| | | | - Monica Monti
- Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy
| | - Serena Ludovisi
- Infectious Diseases Research Laboratories, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
| | - Laura Gragnani
- Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy
| | - Milica Mitrevski
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Jessica Ranieri
- Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy
| | - Elisa Fognani
- Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy
| | - Alessia Piluso
- Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy
| | - Massimo Granata
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Annalisa De Silvestri
- Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
| | - Valeria Scotti
- Clinical Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
| | - Mario U Mondelli
- Infectious Diseases Research Laboratories, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy
| | - Anna Linda Zignego
- Research Center for Systemic Manifestations of Hepatitis Viruses, Department of Internal Medicine, University of Firenze, Firenze, Italy
| | - Massimo Fiorilli
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy
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Gupta A, Quigg RJ. Glomerular Diseases Associated With Hepatitis B and C. Adv Chronic Kidney Dis 2015; 22:343-51. [PMID: 26311595 DOI: 10.1053/j.ackd.2015.06.003] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 06/10/2015] [Accepted: 06/12/2015] [Indexed: 02/08/2023]
Abstract
Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are prevalent worldwide. In this review, we discuss the epidemiology, pathogenesis, clinical manifestations, and treatment of HBV- and HCV-related glomerulonephritis (GN). The most common histopathologic presentation of HBV-GN is HBV-associated membranous nephropathy, which usually manifests clinically with varying grades of proteinuria and microscopic hematuria. The pathogenesis is likely to be immune complex mediated; however, other host and viral factors have been implicated. The treatment of HBV-GN revolves around antiviral therapy. Various histologic types of glomerular diseases are reported in association with HCV infection, the most frequent being Type 1 membranoproliferative glomerulonephritis, usually in the context of Type 2 mixed cryoglobulinemia. The pathogenesis of HCV-GN can be attributed to glomerular deposition of cryoglobulins or noncryoglobulin-immune complexes. Cryoglobulins typically comprised immunoglobulin Mκ with rheumatoid factor activity. Clinically, patients may present with proteinuria, microscopic hematuria, hypertension, and acute nephritic and/or nephrotic syndrome. The treatment of HCV-GN, especially cryoglobulinemic membranoproliferative glomerulonephritis, encompasses various options including contemporary antiviral therapy with or without conventional and novel immunomodulatory agents.
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Roccatello D, Sciascia S, Baldovino S, Rossi D, Alpa M, Naretto C, Di Simone D, Simoncini M, Menegatti E. A 4-year observation in lupus nephritis patients treated with an intensified B-lymphocyte depletion without immunosuppressive maintenance treatment-Clinical response compared to literature and immunological re-assessment. Autoimmun Rev 2015; 14:1123-30. [PMID: 26244817 DOI: 10.1016/j.autrev.2015.07.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 07/29/2015] [Indexed: 01/05/2023]
Abstract
BACKGROUND B cells (BC) play a critical role in systemic lupus erythematosus (SLE). BC depletion therapy still remains an attractive option, despite the disappointing results of randomized controlled trials (RTCs). METHODS Twelve patients with SLE [3 males, mean age 43.8 yrs (25-55)] with severe multiorgan involvement all including kidney (3 patients with Class IV, 4 with Class III/V and 5 with Class V, according to the International Society of Nephrology/Renal Pathology Society glomerulonephritis classification), skin lesions [10], severe polyarthralgias with arthritis [10], polyserositis [2], and lymphadenopathy [5] have been prospectively treated with an intensified B cell depletion therapy (IBCDT) protocol due to their resistance or intolerance to previous therapy (six cases) or as a front line immunosuppressive treatment in 6 women with unsatisfactory therapeutic compliance or as a specific request of a short-time immunosuppression for gestational perspectives. PROTOCOL Rituximab (RTX) 375 mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2 months, associated with 2 IV administrations of 10mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15mg/kg) followed by oral prednisone (0.8 mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given. RESULTS Patients had been followed-up for a mean of 44.5 (24-93)months. Significant decreases (p<0.05) were found in the levels of ESR (baseline mean value: 55.0mm; 3 months: 36; end of follow-up: 13), anti-dsDNA antibodies (baseline: 185 U; 3 months: 107; end of follow-up: 15), and proteinuria (baseline: 4.9 g/24h; 3 months: 0.97; end of follow-up: 0.22). C4 values (baseline 11 mg/dl) significantly increased (p<0.05) after 3 months (22 mg/dl) and at the end of the follow-up (20mg/dl). Of the 12 patients, 9 (75%) have remained well after one cycle of IBCDT, with no flare (mean 51.6 months [25-93]). Three patients relapsed after 36, 41, and 72 months, respectively. Following re-treatment, they again showed complete remission over 18-48 months of observation. CONCLUSIONS A promising role of RTX in an intensified protocol of induction therapy can be envisaged in patients for whom avoiding immunosuppressive maintenance therapy and sparing steroids are particularly appealing. Moreover, our data confirm in one of the longest follow-up available, the opportunity to reconsider the regimens of BL depletion in the treatment of the most severe or refractory forms of SLE despite the disappointing results of RCTs.
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Affiliation(s)
- Dario Roccatello
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy; SCDU Nephrology and Dialysis, S. Giovanni Bosco Hospital, Turin, Italy.
| | - Savino Sciascia
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Simone Baldovino
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Daniela Rossi
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Mirella Alpa
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Carla Naretto
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Debora Di Simone
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Matteo Simoncini
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
| | - Elisa Menegatti
- Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Turin, Italy
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Mazzaro C, Panarello G, Mauro E, Gattei V, Pozzato G. Efficacy and safety of pegylated interferon plus ribavirin for the treatment of hepatitis C virus-positive cryoglobulinemic glomerulonephritis. Dig Liver Dis 2015; 47:613-6. [PMID: 25890508 DOI: 10.1016/j.dld.2015.03.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 03/12/2015] [Accepted: 03/23/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND The most frequent form of renal involvement in patients with hepatitis C infection is cryoglobulinemic membrano-proliferative glomerulonephritis. Nonetheless, some reports indicate that the eradication of the hepatitis C virus may also lead to the remission of this renal disease. METHODS The virological, immunological and nephrological response to pegylated interferon α plus ribavirin (48 weeks in patients infected with genotype 1, and 24 weeks for patients infected with genotypes 2 and 3) was evaluated retrospectively in 10 patients with cryoglobulinemic glomerulonephritis. RESULTS 6 patients obtained end of treatment virological response (60%); during follow-up, 2 relapsed, and 4 patients maintained a sustained virological response (40%). At the end of follow-up, three patients obtained a significant nephrological response and decrease in cryoglobulin levels (p<0.05). No significant changes in clinical and biological parameters were observed in non-responders/relapsers. CONCLUSIONS Eradication of hepatitis C may be associated with the regression of cryoglobulinemic glomerulonephritis.
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Affiliation(s)
- Cesare Mazzaro
- Department of Oncology-Haematology CRO, IRCCS, Aviano, Italy
| | - Giacomo Panarello
- Department of Nephrology, Pordenone General Hospital, Pordenone, Italy
| | - Endri Mauro
- Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
| | - Valter Gattei
- Department of Oncology-Haematology CRO, IRCCS, Aviano, Italy
| | - Gabriele Pozzato
- Clinical Department of Medical and Surgical Sciences, University of Trieste, Trieste, Italy.
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Retamozo S, Brito-Zerón P, Ramos-Casals M. [Treatment of cryoglobulinemic vasculitis associated with hepatitis C virus infection]. Med Clin (Barc) 2015; 144:410-7. [PMID: 24787686 DOI: 10.1016/j.medcli.2014.02.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 02/13/2014] [Accepted: 02/27/2014] [Indexed: 10/25/2022]
Abstract
Cryoglobulinemia is a heterogeneous systemic autoimmune disease with a wide variety of causes, symptoms and outcomes, and different etiopathogenic pathways involved in the vasculitic organ damage. The discovery of the hepatitis C virus (HCV) in 1989 changed radically the focus of research of the so-called "essential" cryoglobulinemia. Cryoglobulins can be detected in 25-30% of patients with HCV, overwhelmingly representing mixed cryoglobulins. However, only 10-15% of patients present with cryoglobulinemic vasculitis, with a broad spectrum of symptoms including mild or life-threatening manifestations. Consequently, not all patients can be uniformly treated. The key therapeutic points in HCV+ patients with cryoglobulinemic vasculitis cover different aspects. The first is to treat the underlying cause of cryoglobulinemia whenever possible, hence the use of antiviral therapies must always be considered in these patients. An individualized diagnostic approach to assess the number of organs involved and the severity of organ involvement is also essential in the therapeutic planning. This complex clinical scenario leads to an equally complex therapeutic scenario. There are three main treatment strategies for HCV-associated cryoglobulinemic vasculitis: conventional immunosuppression, antiviral treatment and biological therapies. The most recent studies are suggesting a change from the classical therapeutic approach (monotherapeutic regimens) to combination/sequential regimens, including treatments targeting the virus and those directed against the induced autoimmune disease, with the aim of blocking the various etiopathogenic pathways involved.
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Affiliation(s)
- Soledad Retamozo
- Laboratorio de Enfermedades Autoinmunes Josep Font, Centro de Investigación Biomédica CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (CELLEX-IDIBAPS), Servicio de Enfermedades Autoinmunes, Institut Clínic de Medicina i Dermatologia (ICMiD), Hospital Clínic, Barcelona. España
| | - Pilar Brito-Zerón
- Laboratorio de Enfermedades Autoinmunes Josep Font, Centro de Investigación Biomédica CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (CELLEX-IDIBAPS), Servicio de Enfermedades Autoinmunes, Institut Clínic de Medicina i Dermatologia (ICMiD), Hospital Clínic, Barcelona. España
| | - Manuel Ramos-Casals
- Laboratorio de Enfermedades Autoinmunes Josep Font, Centro de Investigación Biomédica CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (CELLEX-IDIBAPS), Servicio de Enfermedades Autoinmunes, Institut Clínic de Medicina i Dermatologia (ICMiD), Hospital Clínic, Barcelona. España.
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Lymphoproliferative disease-related mixed cryoglobulinemia treated with rituximab and prednisolone. CEN Case Rep 2015; 4:6-13. [PMID: 28509274 DOI: 10.1007/s13730-014-0130-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Accepted: 05/28/2014] [Indexed: 10/23/2022] Open
Abstract
Mixed cryoglobulinemia is often associated with hepatic C virus infection and is less common with hepatitis B virus infection, and it often progresses into lymphoproliferative diseases. Rituximab is known to achieve systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins in hepatitis C virus-associated cryoglobulinemia. Conversely, there are few reports regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia. We report here the case of a 65-year-old Japanese female who presented with lymphoproliferative disease-related cryoglobulinemia with hepatitis B virus, including membranoproliferative glomerulonephritis with renal failure. The vasculitis was refractory to conventional and antiviral therapy, but rituximab use led to control the disease. Our case highlights the benefit and efficacy of rituximab in association with antiviral therapy in small vessel vasculitis related to lymphoproliferative disease-related cryoglobulinemia with hepatitis B virus.
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Loricera J, Blanco R, Hernández JL, Pina T, González-Vela MC, González-Gay MA. Biologic therapy in ANCA-negative vasculitis. Int Immunopharmacol 2015; 27:213-9. [PMID: 25828585 DOI: 10.1016/j.intimp.2015.03.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Revised: 03/10/2015] [Accepted: 03/14/2015] [Indexed: 01/20/2023]
Abstract
Standard therapeutic schemes for vasculitis are usually associated with numerous side effects and uneven clinical response. However, recent advances in understanding of the pathogenesis of these systemic diseases have resulted in the development of a group of biologic agents potentially useful in patients with vasculitis. Thus, anti-tumor necrosis factor-α drugs may be effective in patients with refractory Kawasaki disease but have failed to do so in giant cell arteritis, and their role in Takayasu arteritis is yet unclear. Preliminary reports on the use of the anti-IL6-receptor antibody, tocilizumab, in large-vessel vasculitis have been encouraging. Interferon alpha has showed positive results in hepatitis B virus-associated polyarteritis nodosa, and hepatitis C virus-induced cryoglobulinemia. Early experience with rituximab in several types of vasculitis has been quite promising, but must be confirmed in ongoing randomized clinical trials. The development of new biologic targeted therapies will probably open a hopeful future for patients with vasculitis.
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Affiliation(s)
- Javier Loricera
- Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, 39008 Santander, Spain
| | - Ricardo Blanco
- Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, 39008 Santander, Spain
| | - José L Hernández
- Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, 39008 Santander, Spain
| | - Trinitario Pina
- Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, 39008 Santander, Spain
| | - M Carmen González-Vela
- Department of Pathology, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, 39008 Santander, Spain
| | - Miguel A González-Gay
- Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, Avenida de Valdecilla s/n, 39008 Santander, Spain.
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Cacoub P, Gragnani L, Comarmond C, Zignego AL. Extrahepatic manifestations of chronic hepatitis C virus infection. Dig Liver Dis 2014; 46 Suppl 5:S165-73. [PMID: 25458776 DOI: 10.1016/j.dld.2014.10.005] [Citation(s) in RCA: 190] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 10/03/2014] [Indexed: 02/09/2023]
Abstract
Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.
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Affiliation(s)
- Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France.
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Sampaio MS, Martin P, Bunnapradist S. Renal dysfunction in end-stage liver disease and post-liver transplant. Clin Liver Dis 2014; 18:543-60. [PMID: 25017075 DOI: 10.1016/j.cld.2014.05.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Renal dysfunction is a frequent complication in patients with end-stage liver disease awaiting orthotopic liver transplantation and in the post-liver transplant period. Although the stereotypical form of renal dysfunction is the hepatorenal syndrome, other causes of acute kidney injury in this population include prerenal azotemia and acute tubular necrosis. Renal injury in a patient with cirrhosis is associated with a poor prognosis.
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Affiliation(s)
- Marcelo S Sampaio
- Division of Nephrology, Department of Medicine, Kidney and Pancreas Transplant Program, David Geffen School of Medicine at UCLA, 1015 Gayley Avenue, Suite 220, Los Angeles, CA 90024, USA
| | - Paul Martin
- Division of Hepatology, Miller School of Medicine, University of Miami, 1500 NW 12 Avenue, Jackson Medical Tower E-1101, Miami, FL 33136, USA
| | - Suphamai Bunnapradist
- Division of Nephrology, Department of Medicine, Kidney and Pancreas Transplant Program, David Geffen School of Medicine at UCLA, 1015 Gayley Avenue, Suite 220, Los Angeles, CA 90024, USA.
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Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol 2014; 20:7544-7554. [PMID: 24976695 PMCID: PMC4069286 DOI: 10.3748/wjg.v20.i24.7544] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 02/08/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.
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Abstract
Hepatitis C virus (HCV) is now well recognised as the main etiologic agent of mixed cryoglobulinaemia vasculitis (cryovas). New opportunities and problems in developing therapy have therefore emerged. Antiviral therapy with pegylated interferon-α and ribavirin (plus protease inhibitor in the case of HCV genotype 1 infection) should be considered as induction therapy for HCV-cryovas with mild to moderate disease severity and activity. An early virologic response to antiviral therapy is correlated with a complete clinical response of HCV-cryovas. In patients presenting with more severe disease (ie, worsening of renal function, mononeuritis multiplex, extensive skin disease including ulcers and distal necrosis), an immunosuppression induction phase is often necessary while awaiting the generally slow response to antiviral treatments. Combination therapy with rituximab plus an optimal antiviral agent is recommended, as it may target the downstream B cell arm of autoimmunity and the viral trigger. Careful monitoring for adverse effects is mandatory, since some manifestations of HCV-cryovas, such as peripheral neuropathy or skin ulcers, may worsen with interferon-based therapy. Clinicians should be aware of the possibility of malignant lymphoma when patients develop a relapse of cryovas without virological relapse. Room for other treatment strategies is very limited. Low-dose corticosteroids may help to control minor intermittent inflammatory signs such arthralgia but do not succeed in case of major organ involvement. Other immunosuppressants should be given only in case of refractory forms of HCV-cryovas, which are frequently associated with an underlying B cell lymphoma.
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Rostaing L, Izopet J, Kamar N. Hepatitis C virus infection in nephrology patients. J Nephropathol 2013; 2:217-33. [PMID: 24475454 PMCID: PMC3891131 DOI: 10.12860/jnp.2013.36] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Accepted: 12/29/2012] [Indexed: 12/19/2022] Open
Abstract
CONTEXT Hepatitis C virus (HCV) infection leads to chronic liver disease, but also to extra-hepatic manifestations. EVIDENCE ACQUISITIONS Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. RESULTS Herein, we provide an overview of renal diseases related to HCV and their therapies, as well as the treatment options available for HCV (+)/RNA (+) dialysis patients. We will not mention, however, HCV infection-related complications in the post-kidney transplantation setting. CONCLUSIONS Extra-hepatic manifestations of HCV infection include mixed cryoglobulinemia, lymphoproliferative disorders, and renal disease. HCV infection has been reported in association with distinct histological patterns of glomerulonephritis in native kidneys.
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Affiliation(s)
- Lionel Rostaing
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
- Department of Virology, CHU Purpan, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France
- INSERM U1043, IFR–BMT, CHU Purpan, Toulouse, France
- Université Paul Sabatier, Toulouse, France
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Affiliation(s)
- Franco Dammacco
- Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
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Renal involvement in HCV-related vasculitis. Clin Res Hepatol Gastroenterol 2013; 37:334-9. [PMID: 23562337 DOI: 10.1016/j.clinre.2013.02.002] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Accepted: 02/07/2013] [Indexed: 02/07/2023]
Abstract
Renal involvement has been frequently reported in the setting of hepatitis C virus (HCV) infection. The most common renal pathology associated with chronic HCV infection is type I membranoproliferative glomerulonephritis associated with type II mixed cryoglobulinemia, while membranoproliferative glomerulonephritis without cryoglobulinemia and membranous nephropathy were less frequently reported. Rarely, focal segmental glomerulosclerosis, fibrillary and immunotactoid glomerulopathies, and thrombotic microangiopathies were described during the course of HCV infection. In the present review, we have focused on renal involvement in HCV-related vasculitis.
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Retamozo S, Díaz-Lagares C, Bosch X, Bové A, Brito-Zerón P, Gómez ME, Yagüe J, Forns X, Cid MC, Ramos-Casals M. Life-Threatening Cryoglobulinemic Patients With Hepatitis C: Clinical Description and Outcome of 279 Patients. Medicine (Baltimore) 2013; 92:273-284. [PMID: 23974248 PMCID: PMC4553974 DOI: 10.1097/md.0b013e3182a5cf71] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Cryoglobulinemia is characterized by a wide range of causes, symptoms, and outcomes. Hepatitis C virus (HCV) infection is detected in 30%-100% of patients with cryoglobulins. Although more than half the patients with cryoglobulinemic vasculitis present a relatively benign clinical course, some may present with potentially life-threatening situations. We conducted the current study to analyze the clinical characteristics and outcomes of HCV patients presenting with life-threatening cryoglobulinemic vasculitis. We evaluated 181 admissions from 89 HCV patients diagnosed with cryoglobulinemic vasculitis consecutively admitted to our department between 1995 and 2010. In addition, we performed a systematic analysis of cases reported to date through a MEDLINE search.The following organ involvements were considered to be potentially life-threatening in HCV patients with cryoglobulinemic vasculitis: cryoglobulinemic, biopsy-proven glomerulonephritis presenting with renal failure; gastrointestinal vasculitis; pulmonary hemorrhage; central nervous system (CNS) involvement; and myocardial involvement. A total of 279 patients (30 from our department and 249 from the literature search) fulfilled the inclusion criteria: 205 presented with renal failure, 45 with gastrointestinal vasculitis, 38 with CNS involvement, 18 with pulmonary hemorrhage, and 3 with myocardial involvement; 30 patients presented with more than 1 life-threatening cryoglobulinemic manifestation. There were 146 (52%) women and 133 (48%) men, with a mean age at diagnosis of cryoglobulinemia of 54 years (range, 25-87 yr) and a mean age at life-threatening involvement of 55 years (range, 25-87 yr). In 232 (83%) patients, life-threatening involvement was the first clinical manifestation of cryoglobulinemia. Severe involvement appeared a mean of 1.2 years (range, 1-11 yr) after the diagnosis of cryoglobulinemic vasculitis. Patients were followed for a mean of 14 months (range, 3-120 mo) after the diagnosis of life-threatening cryoglobulinemia. Sixty-three patients (22%) died. The main cause of death was sepsis (42%) in patients with glomerulonephritis, and cryoglobulinemic vasculitis itself in patients with gastrointestinal, pulmonary, and CNS involvement (60%, 57%, and 62%, respectively). In conclusion, HCV-related cryoglobulinemia may result in progressive (renal involvement) or acute (pulmonary hemorrhage, gastrointestinal ischemia, CNS involvement) life-threatening organ damage. The mortality rate of these manifestations ranges between 20% and 80%. Unfortunately, this may be the first cryoglobulinemic involvement in almost two-thirds of cases, highlighting the complex management and very elevated mortality of these cases.
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Affiliation(s)
- Soledad Retamozo
- From Josep Font Laboratory of Autoimmune Diseases (SR, CDL, AB, PBZ, MEG, MRC) and Vasculitis Research Unit (MCC), Department of Autoimmune Diseases; Department of Internal Medicine (XB); Department of Immunology (JY); and Viral Hepatitis Unit (XF), Department of Hepatology; CIBERehd, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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Gatault P, Philippe G, Jollet I, Isabelle J, Paintaud G, Gilles P, Magdelaine C, Charlotte M, Bridoux F, Franck B, Lebranchu Y, Yvon L, Büchler M, Matthias B, Touchard G, Guy T, Thierry A, Antoine T. Very low residual concentrations of rituximab long after infusion still induce positive B-cell complement-dependent cytotoxicity-crossmatch. Hum Immunol 2013; 74:1616-8. [PMID: 23994588 DOI: 10.1016/j.humimm.2013.08.278] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 08/14/2013] [Accepted: 08/20/2013] [Indexed: 10/26/2022]
Abstract
Rituximab may induce positive B-cell complement-dependent cytotoxicity crossmatch (CDC-XM) in the absence of donor-specific antibodies, as we report in these two cases. We retrospectively assessed the in vitro concentration-effect relationship of rituximab in sera. B-cell CDC-XM results were positive only in the presence of rituximab, even with low concentrations (inferior to 1 μg/mL). Moreover, rituximab neutralization with increasing concentration of an anti-rituximab-idiotype monoclonal antibody progressively reduced B-cell lysis. In conclusion, measurement of rituximab content may be useful to identify sera at risk of misinterpretation in immunized patients.
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Affiliation(s)
| | - Gatault Philippe
- CHRU de Tours, Department of Nephrology and Transplantation, Tours, France; Université François-Rabelais, EA 4245 Tours, France
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50
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Rituximab-based novel strategies for the treatment of immune-mediated glomerular diseases. Autoimmun Rev 2013; 12:854-9. [DOI: 10.1016/j.autrev.2012.09.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2012] [Indexed: 11/23/2022]
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