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Ratiu IA, Mihaescu A, Olariu N, Ratiu CA, Cristian BG, Ratiu A, Indries M, Fratila S, Dejeu D, Teusdea A, Ganea M, Moisa C, Marc L. Hepatitis C Virus Infection in Hemodialysis Patients in the Era of Direct-Acting Antiviral Treatment: Observational Study and Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2093. [PMID: 39768975 PMCID: PMC11678887 DOI: 10.3390/medicina60122093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/16/2024] [Accepted: 12/18/2024] [Indexed: 01/05/2025]
Abstract
Background and Objectives: Hepatitis C virus (HCV) infection is a major global public health concern, particularly in hemodialysis (HD) patients. This study aims to evaluate the demographic, clinical, and laboratory characteristics of HCV-positive patients undergoing HD and assess the long-term impact of direct-acting antivirals (DAAs) on patient outcomes. Moreover, a narrative review aims to summarize the current knowledge regarding HCV treatment in HD patients. The search in the PubMed, Google Scholar, and Scopus databases identified 48 studies relevant to our topic, 18 regarding clinical history and 29 related to HCV treatment. Methods: A retrospective analysis was performed on 165 HD patients from Bihor County HD centers, Romania, between 2014 and 2024. The cohort was divided into two groups: 54 patients who tested positive for HCV and 111 controls who were HCV-negative. Data collected from GPs included demographic information, comorbidities, laboratory parameters, and psychological assessments. Outcomes were evaluated at over 5 years after DAA treatment. A literature review was conducted using PubMed and Google Scholar to identify relevant studies on HCV in HD patients from 1989 to 2024. Results: Laboratory results showed similar parameters across groups, except for lower serum cholesterol levels in the HCV-positive DAA-treated group vs. HCV-positive non-treated ones (155.607 mg% vs. 170.174 mg%, p = 0.040) and increased ALT levels when comparing the same groups (29.107 vs. 22.261, p = 0.027), whereas comorbidities did not differ significantly. The incidence of malignancies was significantly higher among HCV-positive compared to HCV-negative patients (20.3% vs. 8.1%, p = 0.023), mainly among those treated with DAAs, highlighted by the multivariate analysis. Cardiovascular disease remains the leading cause of mortality regardless of HCV status or the use of antiviral therapy. Psychological assessments revealed more severe depression in HCV-positive patients compared to their HCV-negative counterparts. Conclusions: HCV infection in the hemodialysis population typically follows a subclinical course. At over five years after DAA therapy, the results indicate a stabilization of the liver function and the absence of major complications. However, the incidence of malignancies remains high in HCV-positive patients.
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Affiliation(s)
- Ioana Adela Ratiu
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
- Nephrology Department, Emergency Clinical Hospital Bihor County, 12 Corneliu Coposu Street, 410469 Oradea, Romania
| | - Adelina Mihaescu
- Department of Internal Medicine II—Division of Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.M.); (N.O.); (L.M.)
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Nicu Olariu
- Department of Internal Medicine II—Division of Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.M.); (N.O.); (L.M.)
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Cristian Adrian Ratiu
- Dentistry Department, Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania;
| | - Bako Gabriel Cristian
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
- Nephrology Department, Emergency Clinical Hospital Bihor County, 12 Corneliu Coposu Street, 410469 Oradea, Romania
| | - Anamaria Ratiu
- Faculty of Dentistry, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Victor Babeș 8, 400347 Cluj-Napoca, Romania;
| | - Mirela Indries
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
- Infectious Diseases Department, Emergency Clinical Hospital, 410167 Bihor County, Romania
| | - Simona Fratila
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Danut Dejeu
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Alin Teusdea
- Faculty of Environmental Protection, University of Oradea, G-ral Magheru 27, 410087 Oradea, Romania;
| | - Mariana Ganea
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Corina Moisa
- Faculty of Medicine and Pharmacy, University of Oradea, 1st December Square 10, 410073 Oradea, Romania; (I.A.R.); (B.G.C.); (M.I.); (S.F.); (D.D.); (M.G.)
| | - Luciana Marc
- Department of Internal Medicine II—Division of Nephrology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (A.M.); (N.O.); (L.M.)
- Center for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
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Kalita D, Deka S, Chamuah K, Ahmed G. Laboratory Evaluation of Hepatitis C Virus Infection in Patients Undergoing Hemodialysis from North East India. J Clin Exp Hepatol 2022; 12:475-482. [PMID: 35535106 PMCID: PMC9077174 DOI: 10.1016/j.jceh.2021.05.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 05/30/2021] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Subjects undergoing hemodialysis have enhanced vulnerability to hepatitis C virus (HCV) infection due to invasive procedures and poor infection control practices. Early detection and treatment are essential to prevent cross-infection and mortality/morbidity. However, common use anti-HCV antibody tests lack the necessary accuracy, and alternative tests (e.g. core antigen detection kits) which are available need to be examined as a viable alternative. METHOD A total of 270 continuous serum samples were collected from patients undergoing dialysis within 15 months of study period. Sequentially, multiple tests were performed - immunochromatography-based rapid test, third-generation ELISA i.e. (anti-HCV antibody detection), fourth-generation ELISA (HCV antigen-antibody combined detection assay), and HCV RNA quantitative real time polymerase chain reaction (qPCR) assay. Diagnostic parameters of serological kits were compared in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and so on. Statistical Package for the Social Sciences was used. RESULTS HCV-combined core antigen-antibody assays performed better than other serological assays in reference to the gold standard HCV RNA. This fourth-generation assay yielded a Kappa value of 0.947 compared with the value of 0.747 and 0.619 for anti-HCV ELISA and rapid detection test. Other parameters such as sensitivity, specificity, PPV, NPV, and so on were also better for fourth-generation ELISA compared with third-generation ELISA and other serological assays. HCV RNA was negative in 7.3% of anti-HCV-positive patients and was detected in 11.4% of anti-HCV ELISA-negative patients. In about 1.6% of HCV RNA-positive cases, fourth-generation ELISA was negative and had low HCV viral load (650 IU/ml and below). Fourth generation ELISA detected additional 7.4% HCV positive cases (compared to third generation kits) and upon cost effective analyis, additional cost to be bear for the better detection (by fourth generation kit) was found to be only INR 27 per 1% increased case detection. CONCLUSION In resource scant setup, screening and follow-up of patients undergoing hemodialysis can be performed by fourth-generation HCV ELISA (antigen-antibody combined assay) instead of the current practice of anti-HCV antibody ELISA. Better yield in detection rate will compensate for slight addition to costs.
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Key Words
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- CI, confidence interval
- GGT, gamma-glutamyl transferase
- HBV, hepatitis B virus
- HBsAg, hepatitis B virus surface antigen
- HCV RNA
- HCV core antigen
- HCV, hepatitis C virus
- HIV, human immunodeficieny virus
- ICT, immunochromatography
- LQ, lower quartile
- NAT, nucleic acid amplification test
- NPV, negative predictive value
- OCI, occult hepatitis infection
- PCR, polymerase chain reaction
- PPV, positive predictive value
- PWID, persons who inject drug
- RDT, rapid detection test
- SD, standard deviation
- UQ, upper quartile
- anti-HCV antibodies
- dialysis patient
- viral load
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Affiliation(s)
- Deepjyoti Kalita
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Virbhadra Road, Rishikesh 249203, Uttarakhand, India
- Address for correspondence: Dr. Deepjyoti Kalita, Associate Professor, Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Virbhadra Road, Rishikesh 249203, Uttarakhand, India.
| | - Sangeeta Deka
- Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Virbhadra Road, Rishikesh 249203, Uttarakhand, India
| | - Kailash Chamuah
- State Level Viral Research and Diagnostic Laboratory (VRDL), Gauhati Medical College & Hospital, Guwahati, PO: Indrapur, 781005, Guwahati, India
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Marticorena Garcia SR, Althoff CE, Dürr M, Halleck F, Budde K, Grittner U, Burkhardt C, Jöhrens K, Braun J, Fischer T, Hamm B, Sack I, Guo J. Tomoelastography for Longitudinal Monitoring of Viscoelasticity Changes in the Liver and in Renal Allografts after Direct-Acting Antiviral Treatment in 15 Kidney Transplant Recipients with Chronic HCV Infection. J Clin Med 2021; 10:jcm10030510. [PMID: 33535495 PMCID: PMC7867050 DOI: 10.3390/jcm10030510] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 01/21/2021] [Accepted: 01/23/2021] [Indexed: 01/07/2023] Open
Abstract
Besides the liver, hepatitis C virus (HCV) infection also affects kidney allografts. The aim of this study was to longitudinally evaluate viscoelasticity changes in the liver and in kidney allografts in kidney transplant recipients (KTRs) with HCV infection after treatment with direct-acting antiviral agents (DAAs). Fifteen KTRs with HCV infection were treated with DAAs (daclatasvir and sofosbuvir) for 3 months and monitored at baseline, end of treatment (EOT), and 3 (FU1) and 12 (FU2) months after EOT. Shear-wave speed (SWS) and loss angle of the complex shear modulus (φ), reflecting stiffness and fluidity, respectively, were reconstructed from multifrequency magnetic resonance elastography data with tomoelastography post-processing. After virus elimination by DAAs, hepatic stiffness and fluidity decreased, while kidney allograft stiffness and fluidity increased compared with baseline (hepatic stiffness change at FU1: -0.14 m/s, p < 0.01, and at FU2: -0.11 m/s, p < 0.05; fluidity at FU1: -0.05 rad, p = 0.04 and unchanged at FU2: p = 0.20; kidney allograft stiffness change at FU1: +0.27 m/s, p = 0.01, and at FU2: +0.30 m/s, p < 0.01; fluidity at FU1 and FU2: +0.06 rad, p = 0.02). These results suggest the restoration of mechanically sensitive structures and functions in both organs. Tomoelastography can be used to monitor the therapeutic results of HCV treatment non-invasively on the basis of hepatic and renal viscoelastic parameters.
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Affiliation(s)
- Stephan R. Marticorena Garcia
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
- Correspondence: ; Tel.: +49-30-450-527082; Fax: +49-30-450-7527911
| | - Christian E. Althoff
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Michael Dürr
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (M.D.); (F.H.); (K.B.)
| | - Fabian Halleck
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (M.D.); (F.H.); (K.B.)
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (M.D.); (F.H.); (K.B.)
| | - Ulrike Grittner
- Institute of Biometry and Clinical Epidemiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch 2, 10178 Berlin, Germany
| | - Christian Burkhardt
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Korinna Jöhrens
- Department of Pathology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;
| | - Jürgen Braun
- Institute for Medical Informatics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany;
| | - Thomas Fischer
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Bernd Hamm
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Ingolf Sack
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
| | - Jing Guo
- Department of Radiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; (C.E.A.); (C.B.); (T.F.); (B.H.); (I.S.); (J.G.)
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Alkadi MM, Abuhelaiqa EA, Elshirbeny MF, Hamdi AF, Fituri OM, Asim M, Alkaabi SR, Derbala MF, Jarman ME, Ashour AM, Nauman A, Al Maslamani YK, Butt AA, Al-Malki HA. Eradication of hepatitis C virus infection in kidney transplant recipients using direct-acting antiviral therapy: Qatar experience. IMMUNITY INFLAMMATION AND DISEASE 2020; 9:246-254. [PMID: 33264509 PMCID: PMC7860605 DOI: 10.1002/iid3.386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 11/05/2020] [Accepted: 11/14/2020] [Indexed: 02/06/2023]
Abstract
Introduction Hepatitis C virus (HCV) infection has detrimental effects on patient and graft survival after kidney transplantation. In the pre‐direct‐acting antiviral (DAA) era, treatment of HCV infection was associated with low response rates, poor tolerance, and increased risk of allograft rejection. However, DAAs have revolutionized HCV treatment. The aims of this study were to determine the impact of DAA on the sustained virologic response (SVR), renal function, and calcineurin inhibitor (CNI) levels and assess the tolerability to treatment in kidney transplant recipients with HCV infection in Qatar. Methods This retrospective study included the medical records of all kidney transplant recipients with confirmed HCV infection before January 1, 2020. All data were obtained from the patients’ electronic medical records; these included patient demographics; virologic responses to treatment; serum creatinine levels during treatment; urine protein to creatinine ratios and CNI levels before, during, and after treatment; and side effects related to DAA therapy. Results A total of 27 kidney transplant recipients with HCV were identified, 23 of whom received DAA therapy. The length of treatment ranged from 12 to 24 weeks, and 52% of patients had HCV genotype 1 infection. The median log10 HCV RNA was 6.6 copies per milliliter. None of the patients had liver cirrhosis, and all of them achieved SVR. There was no statistically significant difference in the glomerular filtration rate before, during, and after treatment. Most patients had stable CNI trough levels during treatment and did not require dose adjustment. Conclusions HCV infection was successfully eradicated by DAA therapy in kidney transplant recipients, with a 100% SVR rate. Moreover, DAA therapy was well‐tolerated, and kidney function remained stable without an increased risk of rejection. These results are expected to drive the eradication of hepatitis C from the entire country.
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Affiliation(s)
- Mohamad M Alkadi
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Essa A Abuhelaiqa
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Mostafa F Elshirbeny
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Ahmed F Hamdi
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Omar M Fituri
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Muhammad Asim
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Saad R Alkaabi
- Division of Gastroenterology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Moutaz F Derbala
- Weill Cornell Medical College in Qatar, Doha, Qatar.,Division of Gastroenterology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Mona E Jarman
- Division of Transplantation Surgery, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Adel M Ashour
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
| | - Awais Nauman
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Yousuf K Al Maslamani
- Weill Cornell Medical College in Qatar, Doha, Qatar.,Division of Transplantation Surgery, Department of Surgery, Hamad Medical Corporation, Doha, Qatar
| | - Adeel A Butt
- Weill Cornell Medical College in Qatar, Doha, Qatar.,Department of Medicine, Hamad Medical Corporation, Doha, Qatar
| | - Hassan A Al-Malki
- Division of Nephrology, Department of Medicine, Hamad Medical Corporation, Doha, Qatar.,Weill Cornell Medical College in Qatar, Doha, Qatar
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Mahmoudvand S, Shokri S, Azaran A, Seyedian SS, Makvandi M, Mirzaei H, Sheikhrobat SB. Seronegative occult hepatitis C infection among hemodialysis patients: A prevalence study. Ther Apher Dial 2020; 25:218-224. [PMID: 32510846 DOI: 10.1111/1744-9987.13535] [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: 04/07/2020] [Revised: 05/24/2020] [Accepted: 06/04/2020] [Indexed: 11/29/2022]
Abstract
The aim of this study was to investigate the prevalence of occult hepatitis C virus (HCV) infection (OCI) among HD patients. Blood samples were taken from 79 HD patients and their sera were evaluated for the presence of anti-HCV. Both the sera and peripheral blood mononuclear cells (PBMCs) were then checked for HCV RNA by nested reverse transcriptase-polymerase chain reaction. Anti-HCV was positive among 4/79 (5.1%) of the patients. From 75 patients who were negative for anti-HCV, 71 (94.7%) patients were also negative for HCV RNA in sera samples but five of them were positive for HCV RNA in PBMCs. Totally, out of 79 patients, HCV RNA was detected in PBMCs of five (6.3%) patients, indicating that these patients had OCI. No significant difference was observed between the frequency of OCI and gender (P-value = .6). HCV genotype in all five cases of OCI was genotype 3a. Our study showed prevalence rate of 6.3% OCI infection in HD patients. Regarding the serious complications and the clinical importance of OCI in HD patients, sensitive diagnostic methods for identifying HCV RNA in the PBMCs should be implemented for all HD patients.
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Affiliation(s)
- Shahab Mahmoudvand
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Somayeh Shokri
- Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Azarakhsh Azaran
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed S Seyedian
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Manoochehr Makvandi
- Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Habibollah Mirzaei
- Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sheida B Sheikhrobat
- Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Pagan J, Ladino M, Roth D. Should My Patient Accept a Kidney from a Hepatitis C Virus-Infected Donor? KIDNEY360 2020; 1:127-129. [PMID: 35372902 PMCID: PMC8809094 DOI: 10.34067/kid.0001012019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Affiliation(s)
- Javier Pagan
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida; and
| | - Marco Ladino
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida; and
- Nephrology Section, Miami Veterans Administration Healthcare System, Miami, Florida
| | - David Roth
- Katz Family Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida; and
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Zhang J, Sun W, Lin J, Tian Y, Ma L, Zhang L, Zhu Y, Qiu W. Long-term follow-up of HCV infected kidney transplant recipients receiving direct-acting antiviral agents: a single-center experience in China. BMC Infect Dis 2019; 19:645. [PMID: 31324230 PMCID: PMC6642594 DOI: 10.1186/s12879-019-4217-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 06/26/2019] [Indexed: 12/18/2022] Open
Abstract
Background Long-term outcome of DAAs therapy in kidney transplant recipients was unknown. Thus, we aimed to evaluate it in a Chinese cohort of HCV-infected kidney transplant recipients. Methods Single-center and retrospective study of HCV-infected kidney transplant recipients initiating an DAAs regimen between January 2015 and December 2017 was conducted. Totally 26 KTX recipients were divided into three groups, including KTX-HD Group, DAA-KTX Group and KTX-DAA Group. On-treatment response was defined as target not detected within 12 weeks. SVR 48, 96 were defined as HCV-RNA negativity 48, 96 weeks after treatment cessation, respectively. Results HCV genotype was predominantly 1b (80.8%), followed by 2a. All (100%) patients achieved on-treatment response. Time to first TnD was 1.9 ± 0.6 weeks, with no significant difference among the three groups. All patients achieved SVR, with an SVR rate of 100.0% (26/26) among the patients who were followed up over 48 weeks after treatment cessation, and the same SVR rate (24/24) among the patients who were followed up over 96 weeks. Trough levels of Tac remained stable under DAAs therapy, without any dose adjustment. Two patients with abnormal GFR before treatment experienced serum creatinine elevation. Other adverse events included nausea, diarrhea, acid regurgitation, bilirubin elevation and edema of lower limbs. All patients recovered after treatment cessation without reductions in dose, or withdrawal of DAAs or immunosuppressive agents. Conclusions HCV genotype 1b and 2a are the only genotypes and 1b is predominant in our center. Antiviral treatment with DAAs in HCV-infected kidney transplant recipients is persistently effective and well tolerated during long-term follow-up. A regular monitoring of renal function in patients who receive DAAs regimens with preexisting impaired renal function is strongly recommended. Furthermore, the trough CNIs levels were recommended to be frequently monitored.
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Affiliation(s)
- Jian Zhang
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Wen Sun
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Jun Lin
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China. .,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China.
| | - Ye Tian
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Linlin Ma
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Lei Zhang
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Yichen Zhu
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
| | - Wei Qiu
- Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, China.,Beijing key laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, China
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8
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Karkout KA, Al Sherif S, Hussein Q, Albawardi A, Boobes Y. Possible acute rejection associated with the use of the new anti-hepatitis C virus medications. Avicenna J Med 2019; 9:32-34. [PMID: 30697524 PMCID: PMC6335885 DOI: 10.4103/ajm.ajm_171_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Hepatitis C virus infection is associated with increased morbidity and mortality. It remains a major challenge for management and treatment, especially in patients with renal transplant. The new direct-acting antiviral agents gave big hopes to both clinicians and patients that they can overcome this challenge without major side effects. Studies recently have supported this claim; however, they are still few, limited, and may give false hopes. In the following case report, we present a case, supported by histological evidence about a possible acute rejection of kidney transplant after treatment with these new medications. This case is limited by the absence of donor-specific antibodies. This report is aimed to increase awareness about the urgent need for further studies.
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Affiliation(s)
- Khaled A. Karkout
- Department of Internal Medicine, Tawam Hospital, Al-Ain, United Arab Emirates
| | - Saleema Al Sherif
- Department of Internal Medicine, Tawam Hospital, Al-Ain, United Arab Emirates
| | - Qutaiba Hussein
- Division of Nephrology, Tawam Hospital, Al-Ain, United Arab Emirates
| | - Alia Albawardi
- Department of Pathology, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates
| | - Yousef Boobes
- Division of Nephrology, Tawam Hospital, Al-Ain, United Arab Emirates
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Iliescu L, Mercan-Stanciu A, Toma L, Ioanitescu E. A SEVERE CASE OF HYPERGLYCEMIA IN A KIDNEY TRANSPLANT RECIPIENT UNDERGOING INTERFERON-FREE THERAPY FOR CHRONIC HEPATITIS C. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2018; 14:533-538. [PMID: 31149309 PMCID: PMC6516407 DOI: 10.4183/aeb.2018.533] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
CONTEXT Hepatitis C and diabetes represent important health problems globally. The new-onset diabetes after transplantation is a particular entity that appears due to the use of immunosuppression among transplanted patients. OBJECTIVE We aim to describe the clinical and biological aspects of severe hyperglycemia in a kidney transplant recipient undergoing Interferon-free therapy for chronic hepatitis C, discussing the interference of different factors with the glucose metabolism. DESIGN The occurrence of diabetes in a patient with history of renal transplantation and Interferon-free treated hepatitis C was studied from both clinical and paraclinical points of view. SUBJECTS AND METHODS When presenting to the hospital, extensive blood tests were performed on the patient, revealing significant hyperglycemia and an elevated level of blood tacrolimus. Creatinine clearance was calculated. ECG presented T-wave alterations. Intensive insulin protocol was applied, the case being managed in a multidisciplinary approach. RESULTS Blood glucose and tacrolimus were slowly normalized, under therapy. The antiviral treatment was continued, with the achievement of sustained virologic response. CONCLUSIONS Diabetes mellitus can have many causes, hepatitis C and transplantation both having an impact on glucose metabolism. The association of the three entities should be carefully managed, due to its enhancing effect on morbidity and mortality.
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Affiliation(s)
- L. Iliescu
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
| | - A. Mercan-Stanciu
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
| | - L. Toma
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
| | - E.S. Ioanitescu
- Fundeni Clinical Institute, Dept. of Internal Medicine, Bucharest, Romania
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10
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Morikawa K, Nakamura A, Shimazaki T, Sakamoto N. Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic hepatitis C: current evidence. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:2749-2756. [PMID: 30233138 PMCID: PMC6132225 DOI: 10.2147/dddt.s133697] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Treatments for hepatitis C virus (HCV) have advanced greatly, becoming more efficacious with fewer adverse events, due to the availability of direct-acting antiviral agents, which target specific steps in the HCV life cycle. Recently, a combination regimen consisting of the HCV nonstructural protein 5A inhibitor elbasvir (EBR) and the HCV NS3/4A protease inhibitor grazoprevir (GZR) was approved for the treatment of patients with chronic HCV and genotypes (Gts) 1 and 4 in various countries. In Phase III trials, the combination of EBR/GZR (fixed-dose combination table or single agent) for 12 or 16 weeks of treatment with or without ribavirin resulted in a high sustained virological response at 12 weeks in treatment-naïve and treatment-experienced patients with HCV Gt 1a, 1b, 4, or 6, including special populations, such as individuals with advanced chronic kidney disease, HCV-HIV coinfection, and compensated cirrhosis. In this review, we focus on the mode of action, pharmacokinetics, clinical applications, efficacy, and safety profile of EBR/GZR, including special populations who have been considered refractory from the extensive evidence of clinical trials.
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Affiliation(s)
- Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan,
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan,
| | - Tomoe Shimazaki
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan,
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido University Faculty of Medicine and Graduate School of Medicine, Sapporo, Japan,
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11
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Naghdi R, Ranjbar M, Bokharaei-Salim F, Keyvani H, Savaj S, Ossareh S, Shirali A, Mohammad-Alizadeh A. Occult Hepatitis C Infection Among Hemodialysis Patients: A Prevalence Study. Ann Hepatol 2018; 16:510-513. [PMID: 28611267 DOI: 10.5604/01.3001.0010.0277] [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] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Occult hepatitis C infection (OHCI) is the presence of HCV-RNA in the liver or peripheral blood mononuclear cells (PBMC) accompanying with negative serologic results. The aim of this study was to evaluate the prevalence of OHCI among Iranian chronic hemodialysis (HD) patients. MATERIAL AND METHODS In this cross sectional study 200 chronic HD patients with negative HCV antibody enrolled the study. Blood sample of patients were obtained, followed by Polymerase Chain reaction (PCR) testing for detection of HCV RNA. Patients with positive serum HCV RNA were considered as manifest hepatitis C infection (MHCI). However, patients with negative serum HCV RNA underwent further tests on PBMCs for detection of OHCI. RESULTS Serum HCV RNA was positive in 2 (1%) patients whom considered as MHCI, and 6 (3.03%) patients had positive PBMC HCV RNA. CONCLUSION In conclusion, chronic HD patients have been considered as a high risk group for hepatitis C infection. The results of this study suggest that these patients are also at risk for OHCI. Furthermore, evaluating PBMCs to detect HCV RNA would be a sensitive diagnostic method to find OHCI patients.
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Affiliation(s)
- Reza Naghdi
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Mitra Ranjbar
- Department of Infectious Diseases, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | | | - Hossein Keyvani
- Department of Virology, Iran University of Medical Sciences, Tehran, Iran
| | - Shokoufeh Savaj
- Department of Nephrology, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Shahrzad Ossareh
- Department of Nephrology, Hasheminejad Kidney Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Shirali
- Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Mohammad-Alizadeh
- Department of Gastroenterology and Liver Diseases, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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12
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Mak SK, Sin HK, Lo KY, Lo MW, Chan SF, Lo KC, Wong YY, Ho LY, Wong PN, Wong AKM. Treatment of HCV in renal transplant patients with peginterferon and ribavirin: long-term follow-up. Clin Exp Nephrol 2017; 21:764-770. [PMID: 28083764 DOI: 10.1007/s10157-016-1364-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 11/23/2016] [Indexed: 11/24/2022]
Abstract
BACKGROUND In addition to the observation of an increased viremia among patients with chronic hepatitis C virus (HCV) infection who undergo renal transplantation, fibrosis and necroinflammatory activity have been noted to worsen comparing pre- and post-renal transplantation liver biopsies in some of these patients. Apart from the reported reduced patient and allograft survival rates, post-transplant diabetes mellitus, de novo glomerulonephritis, and an increased overall risk of infection have been observed. However, antiviral therapy for HCV is generally considered contraindicated among patients with solid organ transplants, with the main worry being the risk of acute rejection in relation to the use of interferon. We reported the long-term outcome of four renal transplant patients with chronic HCV infection who received peginterferon-based therapy. METHODS We collected the long-term follow-up data of four patients who completed the therapy with peginterferon in combination with ribavirin. Two of them had renal impairment at baseline. RESULTS With treatment, they had a significant improvement in terms of serum liver transaminase level, and two patients achieved the early virological response and the other two rapid virological response. All four patients achieved sustained virological response, with neither HCV flare up nor renal dysfunction during follow-up for a mean duration of 74.3 months after therapy. CONCLUSIONS These results suggest that sustained HCV virological response may be achieved without allograft dysfunction, in selected renal transplant patients using a peginterferon-based therapy.
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Affiliation(s)
- Siu-Ka Mak
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China.
| | - Ho-Kwan Sin
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Kin-Yee Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Man-Wai Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Shuk-Fan Chan
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Kwok-Chi Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Yuk-Yi Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Lo-Yi Ho
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Ping-Nam Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Andrew K M Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
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13
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Swedan SF. Increased incidence of BK virus viraemia among patients undergoing chronic haemodialysis: a case–control study. J Clin Pathol 2017; 71:360-363. [DOI: 10.1136/jclinpath-2017-204707] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2017] [Revised: 08/24/2017] [Accepted: 09/08/2017] [Indexed: 11/04/2022]
Abstract
AimsIncidence of BK virus (BKV) viraemia, a major risk factor for nephropathy, among patients undergoing chronic haemodialysis remains poorly investigated. This case–control study evaluated the risk of infection by BKV, in addition to hepatitis C virus (HCV) among haemodialysis subjects (n=100), compared with age-matched controls (n=100).MethodsSubjects’ blood plasma samples were subjected to nucleic acid extraction, followed by real-time PCR to evaluate viraemia by BKV and HCV, while sera samples were subjected to ELISA, to identify IgG seropositivity for HCV.ResultsMean age±SD was 47.8±20.4 and 48.9±17.6 years for the haemodialysis and control groups, respectively. BKV and HCV viraemia was observed among 19% versus 8% (OR 2.38, 95% CI 1.09 to 5.18; p=0.023) and 3% versus 0% (p=0.081) of the haemodialysis and control groups, respectively. Mean BK viral load±SD did not vary significantly among the two groups; 914.8±2868 versus 44.30±74.04 copies/mL for the haemodialysis and control groups, respectively (p=0.4041). HCV seropositivity rates were 6% versus 2% (p=0.149), among the haemodialysis and control groups, respectively.ConclusionsSubjects on haemodialysis may be at increased risk of nephropathy due to increased incidence of BK virus reactivations and may require optimisation of immunosuppressive therapy.
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Safety and Efficacy of Treatment of Hepatitis C in Kidney Transplant Recipients With Directly Acting Antiviral Agents. Transplantation 2017; 101:1704-1710. [PMID: 28009781 DOI: 10.1097/tp.0000000000001618] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND With the development of all oral, interferon-free directly acting antiviral (DAA) medications, treatment of hepatitis C virus (HCV) infection in renal transplant recipients is possible, but limited data exists on its safety and efficacy. METHODS We performed a retrospective cohort analysis of patients transplanted at our center with HCV who have been started on DAAs. Primary endpoints included sustained virologic response as defined as negative viral load at 12 weeks postcompletion of therapy and allograft function. RESULTS A total of 31 patients met inclusion criteria. The most commonly used regimen was sofosbuvir and ledipasvir (n = 21). Of the treated patients, 100% had undetectable viral load at the completion of therapy. Of the 31 patients treated, 30 (97%) achieved sustained virologic response. Both graft and patient survivals at most recent follow-up was 100%. There was no significant change in glomerular filtration rate (GFR) before or after therapy (64.2 ± 16.5 mL/min per body surface area before vs. 58.9 ± 17.5 mL/min per body surface area after therapy; P = 0.22); however, 3 patients now have GFR less than 20. A total of 6 (19.3%) of 31 patients had worsening proteinuria during or shortly after therapy. Patients with more than 500 mg/g of proteinuria at the start of treatment were significantly more likely to develop worsening proteinuria than those with less than 500 mg/g of proteinuria at the start of therapy (P < 0.001). Retrospective review of 20 untreated HCV patients did not demonstrate worsening allograft function and proteinuria during a median follow-up time of 1386 days (range, 332-6254). CONCLUSIONS Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.
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15
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Ladino M, Pedraza F, Roth D. Opportunities for treatment of the hepatitis C virus-infected patient with chronic kidney disease. World J Hepatol 2017; 9:833-839. [PMID: 28740594 PMCID: PMC5504358 DOI: 10.4254/wjh.v9.i19.833] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 04/06/2017] [Accepted: 05/05/2017] [Indexed: 02/06/2023] Open
Abstract
The prevalence of hepatitis C virus (HCV) infection amongst patients with chronic kidney disease (CKD) and end-stage renal disease exceeds that of the general population. In addition to predisposing to the development of cirrhosis and hepatocellular carcinoma, infection with HCV has been associated with extra-hepatic complications including CKD, proteinuria, glomerulonephritis, cryoglobulinemia, increased cardiovascular risk, insulin resistance, and lymphoma. With these associated morbidities, infection with HCV is not unexpectedly accompanied by an increase in mortality in the general population as well as in patients with kidney disease. Advances in the understanding of the HCV genome have resulted in the development of direct-acting antiviral agents that can achieve much higher sustained virologic response rates than previous interferon-based protocols. The direct acting antivirals have either primarily hepatic or renal metabolism and excretion pathways. This information is particularly relevant when considering treatment in patients with reduced kidney function. In this context, some of these agents are not recommended for use in patients with a glomerular filtration rate < 30 mL/min per 1.73 m2. There are now Food and Drug Administration approved direct acting antiviral agents for the treatment of patients with kidney disease and reduced function. These agents have been demonstrated to be effective with sustained viral response rates comparable to the general population with good safety profiles. A disease that was only recently considered to be very challenging to treat in patients with kidney dysfunction is now curable with these medications.
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16
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Barsoum RS, William EA, Khalil SS. Hepatitis C and kidney disease: A narrative review. J Adv Res 2017; 8:113-130. [PMID: 28149647 PMCID: PMC5272932 DOI: 10.1016/j.jare.2016.07.004] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2016] [Revised: 07/07/2016] [Accepted: 07/17/2016] [Indexed: 02/07/2023] Open
Abstract
Hepatitis-C (HCV) infection can induce kidney injury, mostly due to formation of immune-complexes and cryoglobulins, and possibly to a direct cytopathic effect. It may cause acute kidney injury (AKI) as a part of systemic vasculitis, and augments the risk of AKI due to other etiologies. It is responsible for mesangiocapillary or membranous glomerulonephritis, and accelerates the progression of chronic kidney disease due to other causes. HCV infection increases cardiovascular and liver-related mortality in patients on regular dialysis. HCV-infected patients are at increased risk of acute post-transplant complications. Long-term graft survival is compromised by recurrent or de novo glomerulonephritis, or chronic transplant glomerulopathy. Patient survival is challenged by increased incidence of diabetes, sepsis, post-transplant lymphoproliferative disease, and liver failure. Effective and safe directly acting antiviral agents (DAAs) are currently available for treatment at different stages of kidney disease. However, the relative shortage of DAAs in countries where HCV is highly endemic imposes a need for treatment-prioritization, for which a scoring system is proposed in this review. It is concluded that the thoughtful use of DAAs, will result in a significant change in the epidemiology and clinical profiles of kidney disease, as well as improvement of dialysis and transplant outcomes, in endemic areas.
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Affiliation(s)
- Rashad S. Barsoum
- Kasr-El-Aini Medical School, Cairo University, Cairo, Egypt
- The Cairo Kidney Center, Cairo, Egypt
| | - Emad A. William
- The Cairo Kidney Center, Cairo, Egypt
- National Research Centre, Cairo, Egypt
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Cholongitas E, Pipili C, Papatheodoridis GV. Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation. World J Hepatol 2017; 9:180-190. [PMID: 28217256 PMCID: PMC5295158 DOI: 10.4254/wjh.v9.i4.180] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Revised: 11/21/2016] [Accepted: 12/07/2016] [Indexed: 02/06/2023] Open
Abstract
Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvir-based regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response (SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current management of CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice.
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Affiliation(s)
- Evangelos Cholongitas
- Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
| | - Chrysoula Pipili
- Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
| | - George V Papatheodoridis
- Evangelos Cholongitas, 4 Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, 54642 Thessaloniki, Greece
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Manuel O, Toso C, Pascual MA. Kidney and Pancreas Transplant Recipients. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00084-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Miyazaki R, Miyagi K. Successful treatment of chronic hepatitis C virus genotype 1b infection of a patient with compensated cirrhosis after renal transplantation using daclatasvir-asunaprevir combination therapy: a case report and literature review. RENAL REPLACEMENT THERAPY 2016. [DOI: 10.1186/s41100-016-0075-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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20
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Vionnet J, Saouli AC, Pascual M, Stucker F, Decosterd LA, Moradpour D, Chtioui H. Therapeutic drug monitoring for sofosbuvir and daclatasvir in transplant recipients with chronic hepatitis C and advanced renal disease. J Hepatol 2016; 65:1063-1065. [PMID: 27469899 DOI: 10.1016/j.jhep.2016.06.032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 06/27/2016] [Indexed: 12/04/2022]
Affiliation(s)
- Julien Vionnet
- Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland; Service of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
| | - Anne-Catherine Saouli
- Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Manuel Pascual
- Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Fabien Stucker
- Service of Nephrology, Hôpital de la Providence, Neuchâtel, Switzerland
| | - Laurent Arthur Decosterd
- Laboratory of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Darius Moradpour
- Service of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Haithem Chtioui
- Division of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
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Abstract
Soon after the hepatitis C virus (HCV) was identified in 1989, it was recognized that the prevalence of infection in patients with ESRD far exceeded that in the general population. Infection with HCV predisposes to the hepatic complications of cirrhosis and hepatocellular carcinoma. However, important extrahepatic manifestations include immune complex glomerular disease, accelerated progression of CKD, increases in cardiovascular event risk, and lymphoproliferative disorders. Advances in understanding the molecular biology of HCV have ushered in a new era in the treatment of this infection. Second generation direct-acting antiviral agents have revolutionized therapy, with sustained virologic response rates (undetectable viral load 12 weeks after completing therapy) of >90% in most patients. Studies using direct-acting antivirals in patients with CKD and those on dialysis are showing excellent safety and efficacy as well. In this context, it is imperative that nephrologists become familiar with this literature, reviewed here, so that the important decisions, including which patients should be treated and the optimal timing to initiate therapy, are vetted in association with the compounding issues of CKD, ESRD, and kidney transplantation.
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Affiliation(s)
- Marco Ladino
- Division of Nephrology and Hypertension, University of Miami Miller School of Medicine and the Miami Veterans Administration Hospital, Miami, Florida
| | - Fernando Pedraza
- Division of Nephrology and Hypertension, University of Miami Miller School of Medicine and the Miami Veterans Administration Hospital, Miami, Florida
| | - David Roth
- Division of Nephrology and Hypertension, University of Miami Miller School of Medicine and the Miami Veterans Administration Hospital, Miami, Florida
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Treatment efficacy and tolerability of Sofosbuvir and Ribavirin for chronic hepatitis C infection in post renal transplant patients – A retrospective single centre study. INDIAN JOURNAL OF TRANSPLANTATION 2016. [DOI: 10.1016/j.ijt.2016.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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Finally, safe and effective treatment options for hepatitis C in hemodialysis patients. J Hepatol 2016; 65:7-10. [PMID: 27072190 DOI: 10.1016/j.jhep.2016.04.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 04/04/2016] [Indexed: 01/15/2023]
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Desnoyer A, Pospai D, Lê MP, Gervais A, Heurgué-Berlot A, Laradi A, Harent S, Pinto A, Salmon D, Hillaire S, Fontaine H, Zucman D, Simonpoli AM, Muret P, Larrouy L, Bernard Chabert B, Descamps D, Yazdanpanah Y, Peytavin G. Pharmacokinetics, safety and efficacy of a full dose sofosbuvir-based regimen given daily in hemodialysis patients with chronic hepatitis C. J Hepatol 2016; 65:40-47. [PMID: 26952005 DOI: 10.1016/j.jhep.2016.02.044] [Citation(s) in RCA: 141] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 02/24/2016] [Accepted: 02/26/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) infection is an independent risk factor for chronic kidney disease and leads to faster liver disease progression in patients requiring hemodialysis than in those with normal renal function. Little is known about the use of a sofosbuvir-containing regimen for infected patients on hemodialysis. We aimed to describe the pharmacokinetics, safety and efficacy of sofosbuvir in 2 dosing regimens and associated antiviral agents in HCV-infected patients requiring hemodialysis. METHODS Multicenter, prospective and observational study of patients receiving sofosbuvir, 400mg once daily (n=7) or 3 times a week (n=5), after hemodialysis with simeprevir, daclatasvir, ledipasvir or ribavirin was conducted. Drug plasma concentrations were determined by liquid chromatography-tandem mass spectrometry before and after a 4h hemodialysis and 1.5h after last drug intake at the end of hemodialysis. RESULTS Plasma concentrations of sofosbuvir or its inactive metabolite sofosbuvir-007 did not accumulate with either regimen between hemodialysis sessions or throughout the treatment course. Sofosbuvir-007 extraction ratio (52%) was consistent with historical data. In one patient receiving the once daily regimen, sofosbuvir-007 half-life was slightly higher (38h) than for patients with normal renal function receiving a full dose. Hemodialysis did not remove any other associated anti-HCV agents. Clinical and biological tolerance was good for all patients. Two relapses occurred with the 3 times a week regimen and none with the once daily. CONCLUSIONS A regimen including sofosbuvir, 400mg once daily, could be proposed for HCV-infected patients requiring hemodialysis and should be associated with close clinical, biological, cardiovascular, and therapeutic drug monitoring. LAY SUMMARY Hepatitis C Virus (HCV) infection in hemodialysis patients is prevalent and aggressive. Effective anti-HCV treatment in these patients may stabilize their renal disease. However, sofosbuvir, the cornerstone of most anti-HCV-containing regimens, should not be administered to these patients until more data is available. In this pharmacokinetic study, sofosbuvir full dose (400mg once daily) administered every day with another direct antiviral agent did not accumulate in hemodialysis patients and was safe and effective.
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Affiliation(s)
- Aude Desnoyer
- Pharmaco-Toxicology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France.
| | - Dan Pospai
- Gastroenterology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | - Minh Patrick Lê
- Pharmaco-Toxicology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | - Anne Gervais
- Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | | | | | - Stanislas Harent
- Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | - Adriana Pinto
- Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | - Dominique Salmon
- Internal Medicine Department, Cochin Hospital, APHP, Paris Descartes University, Sorbonne Paris Cité, Paris, France
| | - Sophie Hillaire
- Gastroenterology Department, Foch Hospital, Suresnes, France
| | - Hélène Fontaine
- Gastroenterology Department, Cochin Hospital, APHP, Paris Descartes University, Sorbonne Paris Cité, Inserm U1016, Paris, France
| | - David Zucman
- Infectious Diseases Department, Foch Hospital, Suresnes, France
| | | | - Patrice Muret
- Clinical Pharmaco-Toxicology Department, University Hospital of Besançon, INSERM U1098, Besançon, France
| | - Lucile Larrouy
- Virology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France
| | | | - Diane Descamps
- Virology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France
| | - Yazdan Yazdanpanah
- Infectious Diseases & Tropical Department, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | - Gilles Peytavin
- Pharmaco-Toxicology Department, Bichat-Claude Bernard Hospital, APHP, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, IAME, INSERM UMR 1137, Paris, France
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25
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Sasaki R, Kanda T, Yasui S, Haga Y, Nakamura M, Yamato M, Wu S, Nakamoto S, Arai M, Mikami S, Miyauchi H, Matsubara H, Yokosuka O. Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation. Case Rep Gastroenterol 2016; 10:248-56. [PMID: 27462193 PMCID: PMC4939684 DOI: 10.1159/000445374] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection leads to acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following kidney transplantation, HCV increases the risk of graft loss and patient mortality compared with uninfected patients. The achievement of a sustained virological response with antiviral therapy improves survival and diminishes the risk of hepatic decompensation in HCV patients after a kidney transplant. It has been reported that direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of HCV in patients who are liver transplant recipients. In the present study, we investigated HCV eradication via interferon-free therapies with DAAs in two HCV patients with advanced liver fibrosis following renal transplantation. In both cases, the interferon-free regimens with DAAs were effective in eradicating HCV in the patients after kidney transplantation. No adverse events caused by interferon were identified with the exception of anemia. Interferon-free regimens with DAAs for recurrent HCV in patients following kidney transplantation are relatively safe and effective. However, attention should be focused on anemia during these treatments.
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Affiliation(s)
- Reina Sasaki
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Yuki Haga
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Mutsumi Yamato
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan; Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan
| | - Hideaki Miyauchi
- Department of Frontier Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
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Pedraza F, Ladino M, Roth D. Impact of grazoprevir and elbasvir in the treatment of hepatitis C virus-infected patients with chronic kidney disease and end-stage renal disease. Clin Liver Dis (Hoboken) 2016; 7:112-115. [PMID: 31041043 PMCID: PMC6490272 DOI: 10.1002/cld.549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 03/01/2016] [Accepted: 03/14/2016] [Indexed: 02/04/2023] Open
Affiliation(s)
- Fernando Pedraza
- Miami Veterans Administration Medical Center, and University of Miami Miller School of MedicineMiamiFL
| | - Marco Ladino
- Miami Veterans Administration Medical Center, and University of Miami Miller School of MedicineMiamiFL
| | - David Roth
- Division of Nephrology and HypertensionUniversity of Miami Miller School of MedicineMiamiFL
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Hepatitis C virus infection in nonliver solid organ transplant candidates and recipients. Curr Opin Organ Transplant 2015; 20:259-66. [PMID: 25944237 DOI: 10.1097/mot.0000000000000195] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE OF REVIEW Transplantation is the best treatment for many patients with end-stage organ failure. Hepatitis C infection is prevalent among solid organ candidates and recipients and continues to represent a major source of morbidity and mortality. Prior interferon (IFN)-based therapies have been associated with limited efficacy and high rates of adverse events. Furthermore, prior IFN-based regimens are associated with high rates of allograft rejection limiting their use post-transplant. This review will outline the limited experience with current treatment regimens and how to incorporate the new hepatitis C virus (HCV) treatment regimens. RECENT FINDINGS The introduction of new direct-acting antiviral (DAA) agents against HCV has dramatically altered the landscape of treatment for HCV. Different all-oral regimens are currently available and are rapidly becoming the standard for treating patients with chronic hepatitis C. Excluding patients with liver disease or those who received liver transplant, those regimens have not been studied in patients awaiting solid organ transplant, or those transplanted. SUMMARY The safety and efficacy of DAAs in patients awaiting liver transplant and liver transplant recipients provide us with some insight and guidance on how to use those all-oral IFN-free regimens to allow effective treatment for patients who received or are awaiting nonliver solid organ transplants.
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Hüsing A, Kabar I, Schmidt HH, Heinzow HS. Hepatitis C in Special Patient Cohorts: New Opportunities in Decompensated Liver Cirrhosis, End-Stage Renal Disease and Transplant Medicine. Int J Mol Sci 2015; 16:18033-53. [PMID: 26251895 PMCID: PMC4581234 DOI: 10.3390/ijms160818033] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 07/16/2015] [Accepted: 07/27/2015] [Indexed: 12/16/2022] Open
Abstract
Worldwide, hepatitis C virus (HCV) is a common infection. Due to new antiviral approaches and the approval of direct-acting antiviral agents (DAA), HCV therapy has become more comfortable. Nevertheless, there are special patient groups, in whom treatment of HCV is still challenging. Due to only few data available, tolerability and efficacy of DAAs in special patient cohorts still remain unclear. Such special patient cohorts comprise HCV in patients with decompensated liver disease (Child-Pugh Class B or C), patients with chronic kidney disease, and patients on waiting lists to renal/liver transplantation or those with HCV recurrence after liver transplantation. HCV infection in these patient cohorts has been shown to be associated with increased morbidity and mortality and may lead to reduced graft survival after transplantation. Successful eradication of HCV results in a better outcome concerning liver-related complications and in a better clinical outcome of these patients. In this review, we analyze available data and results from recently published literature and provide an overview of current recommendations of HCV-therapy regimen in these special patient cohorts.
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Affiliation(s)
- Anna Hüsing
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
| | - Iyad Kabar
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
| | - Hartmut H Schmidt
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
| | - Hauke S Heinzow
- Department of Transplant Medicine, University Hospital Muenster, 48149 Münster, Germany.
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29
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Vidales-Braz BM, da Silva NMO, Lobato R, Germano FN, da Mota LD, Barros EJG, de Martinez AMB. Detection of hepatitis C virus in patients with terminal renal disease undergoing dialysis in southern Brazil: prevalence, risk factors, genotypes, and viral load dynamics in hemodialysis patients. Virol J 2015; 12:8. [PMID: 25644891 PMCID: PMC4329191 DOI: 10.1186/s12985-015-0238-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Accepted: 01/02/2015] [Indexed: 01/04/2023] Open
Abstract
UNLABELLED Hepatitis C (HCV) is a serious public health issue, and it is estimated that 3% of the world's population is infected. Patients in hemodialysis units have an increased risk for contracting HCV, and high prevalence rates have been found in hemodialysis units around the world. This study is aimed at determining the prevalence of HCV in patients with terminal chronic renal disease (tCRD) who have been submitted to hemodialysis and peritoneal dialysis in southern Brazil to characterize the most prevalent genotypes, the viral load, and possible risk factors and to assess the validity between the ELISA and RT-PCR detection methods. Of 320 patients from three dialysis units, 318 participated in this study. According to the medical records, 55 patients were reactive to HCV, as determined via ELISA. All 318 samples were submitted to RT-PCR and genotyped using an Abbott Realtime m2000 system. Data obtained through a questionnaire and chemical variables were associated with the HCV. RESULTS The prevalence of HCV was 18.24% (58), and the concordance between the HCV serology and the RT-PCR was 94%. Three patients were diagnosed to be negative for HCV using the ELISA assay but positive when using RT-PCR. Genotype 1 was the most prevalent (46.7%) genotype, within which subtype 1a was the most frequent (74.1%). One of the risk factors associated with HCV infection was the length of time that the patient had been undergoing hemodialysis treatments (p < 0.001). Additionally, the viral load was found to vary when tested before and after hemodialysis (p < 0.001). CONCLUSION The prevalence of HCV in dialysis units continues to remain high, indicating nosocomial contamination. RT-PCR detected the presence of the hepatitis C virus in patients with a non-reactive serology, which highlights the importance of performing molecular tests on dialysis patients. The variation in the viral load in patients submitted to hemodialysis indicates a possible destruction or gripping of viral particles to the dialyzer membrane.
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Affiliation(s)
| | | | - Rubens Lobato
- Federal University of Rio Grande (FURG), Rio Grande, Brazil.
| | | | | | - Elvino J G Barros
- Federal University of Rio Grande do Sul (UFRGS), Porto alegre, Brazil.
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Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C virus infection and kidney transplantation in 2014: what's new? Am J Transplant 2014; 14:2206-20. [PMID: 25091274 DOI: 10.1111/ajt.12835] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 05/15/2014] [Accepted: 05/16/2014] [Indexed: 01/25/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.
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Affiliation(s)
- S Baid-Agrawal
- Department of Nephrology and Medical Intensive Care, Campus Virchow-Klinikum, Charité Universitaetsmedizin Berlin, Berlin, Germany
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31
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Xia Y, Friedmann P, Yaffe H, Phair J, Gupta A, Kayler LK. Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses. Am J Transplant 2014; 14:2037-47. [PMID: 25098499 DOI: 10.1111/ajt.12847] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2013] [Revised: 03/21/2014] [Accepted: 03/27/2014] [Indexed: 01/25/2023]
Abstract
Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV- n = 1700; HIV- n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04-1.47) and patient survival (aHR 1.24, 95% CI 1.06-1.45) compared with HCV-. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48-1.51) and patient survival (aHR 0.80, 95% CI 0.39-1.64) compared with HIV-. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival.
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Affiliation(s)
- Y Xia
- Department of Surgery, Montefiore Medical Center, Bronx, NY; Department of Surgery, Albert Einstein College of Medicine, Bronx, NY
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32
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Baid-Agrawal S, Schindler R, Reinke P, Staedtler A, Rimpler S, Malik B, Frei U, Berg T. Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients. J Hepatol 2014; 60:928-33. [PMID: 24447875 DOI: 10.1016/j.jhep.2014.01.012] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Revised: 01/13/2014] [Accepted: 01/13/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Detection of hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in absence of HCV RNA in serum, designated as 'occult HCV infection', has been a matter of controversy in recent years. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) and kidney transplant (KTx) patients. METHODS We enrolled 417 CHD patients, 417 KTx recipients and 2 control groups - 25 anti-HCV (antibody against HCV)-positive and HCV RNA-positive patients with chronic hepatitis C, and 40 anti-HCV-, HCV RNA-, and HBsAg-negative healthy subjects. HCV RNA was tested in serum and PBMC using a sensitive commercial assay. RESULTS In CHD patients, the prevalence of anti-HCV was 3.6% (15/417) and of positive serum HCV RNA 2.4% (10/417). HCV RNA was detected in PBMC in 1/407 (0.25%) HCV serum RNA-negative patients ("occult HCV infection"). In KTx recipients, prevalence of anti-HCV was 4.8% (20/417) and of positive serum HCV RNA 4.6% (19/417). Occult HCV infection was found in 2/398 (0.5%) serum HCV RNA-negative patients. On a mean longitudinal follow-up of 30months of the 3 patients with occult HCV infection, there was no clinical or virological evidence of HCV infection. CONCLUSIONS The prevalence of occult HCV infection was very low in our CHD and KTx patients, and it did not appear to be clinically relevant. Further studies in geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups.
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Affiliation(s)
- Seema Baid-Agrawal
- Dept of Nephrology and Medical Intensive Care, Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Germany.
| | - Ralf Schindler
- Dept of Nephrology and Medical Intensive Care, Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Germany
| | - Petra Reinke
- Dept of Nephrology and Medical Intensive Care, Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Germany
| | | | - Sunda Rimpler
- Dept of Internal Medicine, Vivantes Wenckebach Klinikum, Berlin, Germany
| | - Barbara Malik
- Dept of Gastroenterology and Hepatology, Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Germany
| | - Ulrich Frei
- Dept of Nephrology and Medical Intensive Care, Campus Virchow Klinikum, Charite Universitaetsmedizin Berlin, Germany
| | - Thomas Berg
- Dept of Hepatology, Universitaetsklinikum Leipzig, Leipzig, Germany
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Méndez-Sánchez N, Ridruejo E, Alves de Mattos A, Chávez-Tapia NC, Zapata R, Paraná R, Mastai R, Strauss E, Guevara-Casallas LG, Daruich J, Gadano A, Parise ER, Uribe M, Aguilar-Olivos NE, Dagher L, Ferraz-Neto BH, Valdés-Sánchez M, Sánchez-Avila JF. Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma. Ann Hepatol 2014; 13 Suppl 1:S4-S40. [PMID: 24998696 DOI: 10.1016/s1665-2681(19)30920-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.
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Affiliation(s)
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC". Ciudad Autónoma de Buenos Aires, Argentina; Hepatology and Liver Transplant Unit. Hospital Universitario Austral, Pilar, Argentina
| | | | | | - Rodrigo Zapata
- Hepatology and Liver Transplantation Unit. University of Chile School of Medicine, German Clinic. Santiago, Chile
| | - Raymundo Paraná
- Associate Professor of School of Medicine - Federal University of Bahia Head of the Gastro-Hepatologist Unit of the University Bahia University Hospital
| | - Ricardo Mastai
- Transplantation Unit. German Hospital.Buenos Aires, Argentina
| | - Edna Strauss
- Clinical hepatologist of Hospital do Coraçao - São Paulo - Brazil. Professor of the Post Graduate Course in the Department of Pathology at the School of Medicine, University of São Paulo
| | | | - Jorge Daruich
- Hepatology Department, Clinical Hospital San Martín. University of Buenos Aires Buenos Aires, Argentina
| | - Adrian Gadano
- Section of Hepatology, Italian Hospital of Buenos Aires. Buenos Aires, Argentina
| | - Edison Roberto Parise
- Professor Associado da Disciplina de Gastroenterologia da Universidade Federal de São Paulo, Presidente Eleito da Sociedade Brasileira de Hepatologia
| | - Misael Uribe
- Digestive Diseases and Obesity Clinic, Medica Sur Clinic Foundation. México City, Mexico
| | - Nancy E Aguilar-Olivos
- Digestive Diseases and Obesity Clinic, Medica Sur Clinic Foundation. México City, Mexico
| | - Lucy Dagher
- Consultant Hepatologist. Metropolitan Policlinic- Caracas- Venezuela
| | - Ben-Hur Ferraz-Neto
- Director of Liver Institute - Beneficencia Portuguesa de São Paulo. Chief of Liver Transplantation Team
| | - Martha Valdés-Sánchez
- Department of Pediatric Oncology National Medical Center "Siglo XXI". Mexico City, Mexico
| | - Juan F Sánchez-Avila
- Hepatology and Liver Transplantation Department National Institute of Nutrition and Medical Sciences "Salvador Zubirán" Mexico City, Mexico
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Vivanco M, Friedmann P, Xia Y, Klair T, Marfo K, de Boccardo G, Greenstein S, Chapochnick-Friedmann J, Kinkhabwala M, Ajaimy M, Lubetzky ML, Akalin E, Kayler LK. Campath induction in HCV and HCV/HIV-seropositive kidney transplant recipients. Transpl Int 2013; 26:1016-26. [DOI: 10.1111/tri.12167] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Revised: 04/29/2013] [Accepted: 07/21/2013] [Indexed: 01/15/2023]
Affiliation(s)
- Marcelo Vivanco
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
| | - Patricia Friedmann
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
| | - Yu Xia
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
| | - Tarunjeet Klair
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
| | - Kwaku Marfo
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
| | | | - Stuart Greenstein
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
| | - Javier Chapochnick-Friedmann
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
| | - Milan Kinkhabwala
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
| | - Maria Ajaimy
- Department of Medicine; Montefiore Medical Center; Bronx NY USA
| | | | - Enver Akalin
- Department of Medicine; Montefiore Medical Center; Bronx NY USA
| | - Liise K. Kayler
- Department of Surgery; Montefiore Medical Center; Bronx NY USA
- Department of Surgery; Albert Einstein College of Medicine; Bronx NY USA
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da Silva NMO, Germano FN, Mendoza-Sassi RA, Seuánez HN, Soares MA, de Martinez AMB. Evidence of association between hepatitis C virus genotype 2b and nosocomial transmissions in hemodialysis centers from southern Brazil. Virol J 2013; 10:167. [PMID: 23714239 PMCID: PMC3680315 DOI: 10.1186/1743-422x-10-167] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 05/17/2013] [Indexed: 12/29/2022] Open
Abstract
Background Hepatitis C virus infection is a serious public health problem. Hemodialysis is considered one of the main risk factors of HCV infection, due to several invasive medical procedures and potential nosocomial transmission that patients with chronic renal failure (CRF) are continuously submitted. The aims of this study were to determine the prevalence of HCV and its genotypes in patients with CRF in hemodialysis units in southern Brazil. Methods Demographic data and risk factors for HCV transmission were collected and analyzed. These data were obtained from patients undergoing hemodialysis treatment from January 2009 to August 2010, on two dialysis units of Rio Grande, southern Brazil. Genotyping was carried out by sequencing analysis of HCV NS5b, core-E1 junction and 5′UTR genomic regions. Results One hundred fifty-nine patients under regular hemodialysis treatment were studied. HCV prevalence was 23.3%. HCV-infected patients had been on dialysis treatment for 91.9 months, a more prolonged period compared to HCV-negative patients (p = 0.001). While HCV genotypes 1b and 3a were identified as the most frequent strains, a surprisingly high proportion of genotype 2b was observed among patients in one of the dialysis centers compared to the general HCV-infected population of the same area. Hemodialysis treatment exposure time and healthcare working were associated with HCV infection. Conclusions Besides the efforts to minimize nosocomial transmission of HCV, some events of transmission are still evidenced in dialysis units.
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Hepatitis C infection and chronic renal diseases. Hepatol Int 2013. [PMID: 26201619 DOI: 10.1007/s12072-012-9356-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
Hepatitis C virus (HCV) infection and chronic renal diseases can be linked in two different ways. Some forms of renal disease are precipitated by HCV infection, while patients with end-stage renal disease are at increased risk for acquiring HCV infection. Patients with chronic HCV infection and renal disease have a poor prognosis. Most studies on treatment of HCV and renal diseases have been uncontrolled trials with small number of subjects. So, there is a lack of evidence-based recommendations and guidelines on the management of this condition. In this review, we will attempt to provide the most recent insights on HCV infection both as a extrahepatic manifestations and as a complication of end-stage renal patients.
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Song ZL, Cui YJ, Zheng WP, Teng DH, Zheng H. Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues. World J Gastroenterol 2012; 18:7149-7157. [PMID: 23326119 PMCID: PMC3544016 DOI: 10.3748/wjg.v18.i48.7149] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 11/02/2012] [Accepted: 11/06/2012] [Indexed: 02/06/2023] Open
Abstract
Nucleos(t)ide analogues (NA) are a breakthrough in the treatment and management of chronic hepatitis B. NA could suppress the replication of hepatitis B virus (HBV) and control the progression of the disease. However, drug resistance caused by their long-term use becomes a practical problem, which influences the long-term outcomes in patients. Liver transplantation is the only choice for patients with HBV-related end-stage liver disease. But, the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients. Recently, the multi-drug resistance (MDR) has become a common issue raised due to the development and clinical application of a variety of NA. This may complicate the antiviral therapy and bring poorly prognostic outcomes. Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR, the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy. The future of HBV researches relies on how to prevent the MDR occurrence and develop reasonable and effective treatment strategies. This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.
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Analysis of the association of an MMP1 promoter polymorphism and transcript levels with chronic periodontitis and end-stage renal disease in a Brazilian population. Arch Oral Biol 2012; 57:954-63. [DOI: 10.1016/j.archoralbio.2012.01.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2011] [Revised: 01/17/2012] [Accepted: 01/28/2012] [Indexed: 11/17/2022]
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Abstract
The management of hepatitis B in liver transplantation has evolved significantly over the past 2 decades. Introduction of hepatitis B immune globulin and subsequently nucleos(t)ide analogues has revolutionized transplantation for hepatitis B virus (HBV), increasing survival for patients transplanted for this indication. With the availability of new and potent antivirals for HBV, the need for liver transplant should continue to decrease in the coming years. Moreover, the newer antivirals with high resistance barriers will allow effective long-term viral prophylaxis and therefore, prevention of recurrence.
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Affiliation(s)
- Corinne Buchanan
- Center for Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Pipili C, Ilonidis G, Cholongitas E. Hepatitis C virus and kidney: a strong association with different clinical aspects. Liver Int 2011; 31:1071-80. [PMID: 21745269 DOI: 10.1111/j.1478-3231.2011.02458.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
The most frequent kidney disease associated with chronic hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis in patients with type II mixed cryoglobulinaemia. The principal clinical manifestations of glomerular disease in HCV-infected patients are the presence of proteinuria and haematuria with or without impaired kidney function. Pharmaceutical regimens vary because the main pathogenesis of renal dysfunction often mediated by cryoglobulins has not been fully elucidated. HCV infection remains common in patients on renal replacement therapy and has an adverse impact on their survival. Safe and effective pharmaceutical regimens have not been yet established and nosocomial spread within dialysis units continues to occur. Monotherapy with interferon for HCV infection is probably more effective in dialysis than in non-uraemic patients, while experience with ribavirin is limited because of its adverse haemolytic effect. Based on shortage of cadaver kidneys and the fact that HCV renal transplant recipients have better survival than stay on maintenance haemodialysis or at list for transplantation, health organization proposed the use of cadaver kidneys from anti-HCV-positive donors, bringing up concerns and conflicting views. This present review describes the main renal manifestations of HCV infection, the epidemiological and clinical characteristics of chronic kidney disease population and comments on the limitations and shortcomings of current therapeutical regiments.
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Affiliation(s)
- Chrisoula Pipili
- Department of Nephrology, Aretaieion University Hospital, Athens, Greece
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Overlapping pathways to transplant glomerulopathy: chronic humoral rejection, hepatitis C infection, and thrombotic microangiopathy. Kidney Int 2011; 80:879-85. [PMID: 21697808 DOI: 10.1038/ki.2011.194] [Citation(s) in RCA: 109] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Transplant glomerulopathy (TG) has received much attention in recent years as a symptom of chronic humoral rejection; however, many cases lack C4d deposition and/or circulating donor-specific antibodies (DSAs). To determine the contribution of other causes, we studied 209 consecutive renal allograft indication biopsies for chronic allograft dysfunction, of which 25 met the pathological criteria of TG. Three partially overlapping etiologies accounted for 21 (84%) cases: C4d-positive (48%), hepatitis C-positive (36%), and thrombotic microangiopathy (TMA)-positive (32%) TG. The majority of patients with confirmed TMA were also hepatitis C positive, and the majority of hepatitis C-positive patients had TMA. DSAs were significantly associated with C4d-positive but not with hepatitis C-positive TG. The prevalence of hepatitis C was significantly higher in the TG group than in 29 control patients. Within the TG cohort, those who were hepatitis C-positive developed allograft failure significantly earlier than hepatitis C-negative patients. Thus, TG is not a specific diagnosis but a pattern of pathological injury involving three major overlapping pathways. It is important to distinguish these mechanisms, as they may have different prognostic and therapeutic implications.
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Zeniya M, Yokoyama K, Imamura N, Murai S, Ishikawa T, Hokari A, Koike K, Takahashi H, Sadaoka S. Significance of interferon-β for the treatment of hepatitis C virus infection in hemodialyzed patients. Hepatol Res 2010; 40:862-9. [PMID: 20887590 DOI: 10.1111/j.1872-034x.2010.00693.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM We evaluated the adverse effects and efficacy associated with interferon-β (IFN-β) for the treatment of hepatitis C virus (HCV) infection in 20 hemodialyzed (HD) patients. METHODS IFN-β was administrated at a dose of 3 MIU three times a week for 24 weeks simultaneously at the time of HD for the patients of genotype 2a whose viral loads were less than 150 KIU/mL and considered to respond well to IFN therapy. RESULTS There was a sustained virological response (SVR) rate of this treatment in 90% of the patients, and sex, age and HD duration had no affect. Slight adverse effects such as fever, malaise and itching were observed during the treatment periods but none serious in any of the patients. Also, no significant difference in adverse effect was observed between 3 MIU and higher dose (6 MIU) groups. CONCLUSION Because IFN-β can be administrated easily into the circuit of HD, adverse effects can be monitored earlier and taken measures against quickly. Taken together, IFN-β-based therapy has a potential for HCV treatment in HD patients but further studies for the patients who have higher viral loads will be required to confirm this.
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Affiliation(s)
- Mikio Zeniya
- Gastroenterology, Jikei University Graduate School of Medicine, Tokyo, Japan
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Amorim RM, Raiol T, Trevizoli JE, Neves FAR, Martins CR, Martins RM. Hepatitis C virus genotypes in hemodialysis patients in the Federal District, Brazil. Rev Inst Med Trop Sao Paulo 2010; 52:57-60. [DOI: 10.1590/s0036-46652010000100010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) genotypes and subtypes were determined in hemodialysis patients in the Federal District, Brazil, by sequencing of the 5' noncoding (NC) and nonstructural 5B (NS5B) regions. From 761 patients, 66 anti-HCV-positive samples were tested for HCV RNA. All 51 HCV RNA-positive samples by PCR of the 5' NC region were genotyped as genotypes 1 (90.2%) and 3 (9.8%). Subtype 1a (82.3%) was the most prevalent, followed by subtypes 3a (9.8%), 1b (5.9%) and 1a/1b (2.0%). Forty-two samples could be amplified and genotyped in the NS5B region: 38 (90.5%) as genotype 1, subtypes 1a, and 8 (9.5%) as genotype 3, subtype 3a. For the 42 samples sequenced in both regions, the genotypes and subtypes determined were concordant in 100% and 95.2% of cases, respectively. Two samples presented discrepant results, with the 5' NC region not distinguishing correctly the subtypes 1a and 1b. These findings indicate that the HCV genotype 1, subtype 1a, is the most prevalent among hemodialysis patients in the Federal District, Brazil.
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Manuel O, Baid-Agrawal S, Pascual M. Kidney transplant patients. Infect Dis (Lond) 2010. [DOI: 10.1016/b978-0-323-04579-7.00080-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Pageaux GP, Hilleret MN, Garrigues V, Bismuth M, Audin-Mamlouk H, Zarski JP, Mourad G. Pegylated interferon-alpha-based treatment for chronic hepatitis C in renal transplant recipients: an open pilot study. Transpl Int 2009; 22:562-7. [PMID: 19175562 DOI: 10.1111/j.1432-2277.2008.00831.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Treatment of hepatitis C in renal transplant recipients remains a controversial issue, as interferon therapy has been associated with a high risk of rejection and poor efficacy. We report here the use of pegylated interferon-alpha, alone or in combination with ribavirin, in renal transplant recipients with chronic hepatitis C. Eight renal transplant recipients with chronic hepatitis C were recruited. The mean delay between renal transplantation and antiviral therapy was 198.8 months. Sustained virological response was observed in four of out eight patients. Three patients with sustained virological response were genotype 2, one was genotype 1; fibrosis stages were F1 for one patient, F2 for 2, F3 for one. At baseline, renal dysfunction was moderate in seven patients and severe in one patient. No patient experienced rejection episodes during or after pegylated interferon-alpha therapy. One patient developed haemolytic uraemic syndrome, which eventually resulted in graft loss and return to dialysis. In conclusion, for renal transplant recipients treated with pegylated interferon-alpha-based therapy, we observed a low risk of renal dysfunction, acceptable tolerance and significant virological efficacy. This is therefore the first study to suggest that pegylated interferon-alpha could be proposed late after transplantation to renal transplant recipients.
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Araoka T, Takeoka H, Nishioka K, Kishi S, Araki M, Kishi F, Shigeta R, Murakami T, Kondo N, Matsuura M, Yoshikawa K, Mima A, Nagai K, Takahashi T, Abe H, Ikeda M, Kondo M, Sugiyama A, Sugano M, Doi T. Safety and efficacy of interferon-beta therapy for hemodialysis patient with HCV. ACTA ACUST UNITED AC 2009. [DOI: 10.4009/jsdt.42.393] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Moghaddam SMH, Alavian SM, Kermani NA. Hepatitis C and renal transplantation: a review on historical aspects and current issues. Rev Med Virol 2008; 18:375-86. [PMID: 18702126 DOI: 10.1002/rmv.590] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Chronic liver disease has a significant impact on the survival of renal transplant recipients with an incidence rate of 4-38%. Approximately, 8-28% of renal transplant recipients die due to chronic liver disease. Hepatitis C seems to be the leading cause of chronic liver disease in kidney recipients. Hepatitis C virus (HCV) infection has a wide range of prevalence (2.6-66%) among renal transplant recipients living in different countries with great genotype diversity in different parts of the world. Nowadays, antiviral drugs are used for the management of hepatitis C. Because of graft-threatening effects of some antiviral drugs used in HCV-infected renal transplant recipients, we specifically focused on HCV treatment after renal transplantation. Treatment of post-renal transplantation chronic liver disease with INF and ribavirin remains controversial. Anecdotal reports on post-renal transplantation hepatitis C demonstrate encouraging findings. This review summarises the most current information on diagnosis, treatment, prognosis, complications as well as the new aspects of treatment in HCV-infected renal transplant recipients. HCV belongs to the family of Flaviviridae, genus Hepacivirus.
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Entecavir Therapy for Adefovir-Resistant Hepatitis B Virus Infection in Kidney and Liver Allograft Recipients. Transplantation 2008; 86:611-4. [DOI: 10.1097/tp.0b013e3181806c8c] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Preventive health care in chronic kidney disease and end-stage renal disease. ACTA ACUST UNITED AC 2008; 4:194-206. [PMID: 18285747 DOI: 10.1038/ncpneph0762] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2007] [Accepted: 01/11/2008] [Indexed: 12/19/2022]
Abstract
The complex care that must be provided for patients with renal disease might interfere with provision of basic preventive measures in this population. Preventive health care, including infection screening and prophylaxis, vaccinations, management of blood glucose and lipid levels, and cancer screening, is important, as it might decrease acute morbidity and mortality. This Review highlights useful preventive and health maintenance strategies for patients with chronic kidney disease and those with end-stage renal disease.
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