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Behera MK, Majji P, Behera S, Pani M, Mohapatro A, Patra UC, Jena SK. The Fixed Dose Combination of Sofosbuvir and Velpatasvir is Safe and Effective in Patients of Chronic Hepatitis C With End-stage Renal Disease. J Clin Exp Hepatol 2024; 14:101367. [PMID: 38558861 PMCID: PMC10981127 DOI: 10.1016/j.jceh.2024.101367] [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] [Received: 10/16/2023] [Accepted: 02/14/2024] [Indexed: 04/04/2024] Open
Abstract
Background The burden of hepatitis C virus (HCV) in India is alarming, with a major share of this virus being witnessed in patients with end-stage renal disease (ESRD). A pan-genotypic combination of sofosbuvir and velpatasvir is found to be safe, effective, and economical in resource-constraint countries such as ours. However, there are scanty data on the efficacy and safety of sofosbuvir and velpatasvir combination in patients with ESRD. Hence, we performed this study to evaluate the safety and efficacy of the combination of sofosbuvir and velpatasvir in patients of chronic hepatitis C (CHC) with ESRD. Methods This is an observational study comprising of 40 CHC patients with ESRD on maintenance hemodialysis. All patients were treated with a fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in case of non-cirrhotic or compensated cirrhosis and 24 weeks in case of decompensated cirrhosis. The efficacy was assessed by sustained virological response defined by negative HCV RNA at 12 weeks (sustained virological response [SVR] 12) post treatment, and safety was assessed by recording any side-effects of all patients. Results Out of the 40 patients enrolled in our study, majority were non-cirrhotic (77%), and all were treatment-naive. The mean age was 49.87 ± 12.13 years, and 80% patients were male. The mean baseline HCV RNA was 2.61 ± 7.83 × 106 IU/ml. All the 40 patients (100%) achieved undetectable HCV RNA at the end of treatment; however, 39 patients (97.5%) achieved SVR 12. There was no significant deterioration of estimated glomerular filtration rate (eGFR) after completion of antiviral therapy as compared to the baseline eGFR (13.27 ± 10.32 vs13.54 ± 11.38, P = 0.54). None of the patients reported any serious adverse effects during treatment. Conclusion The fixed-dose combination of sofosbuvir and velpatasvir is effective and has showed excellent safety profile in patients of CHC with ESRD.
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Affiliation(s)
- Manas K. Behera
- Department of Hepatology, SCB Medical College and Hospital, Cuttack, India
| | - Prabir Majji
- Department of Hepatology, SCB Medical College and Hospital, Cuttack, India
| | - Sanatan Behera
- Department of Hepatology, SCB Medical College and Hospital, Cuttack, India
| | - Manoj Pani
- NVHCP, SCB Medical College and Hospital, Cuttack, India
| | - Arupam Mohapatro
- Department of Hepatology, SCB Medical College and Hospital, Cuttack, India
| | - Umesh C. Patra
- Department of Hepatology, SCB Medical College and Hospital, Cuttack, India
| | - Susanta K. Jena
- Department of Hepatology, SCB Medical College and Hospital, Cuttack, India
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Pacheco LS, Ventura PE, Kist R, Garcia VD, Meinerz G, Tovo CV, Cantisani GPC, Zanotelli ML, Mucenic M, Keitel E. Real-world effectiveness and safety of direct-acting antivirals for the treatment of hepatitis C virus in kidney and liver transplant recipients: experience of a large transplant center in Brazil. Rev Inst Med Trop Sao Paulo 2023; 65:e59. [PMID: 38055377 PMCID: PMC10703500 DOI: 10.1590/s1678-9946202365059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 10/26/2023] [Indexed: 12/08/2023] Open
Abstract
Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.
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Affiliation(s)
- Larissa Sgaria Pacheco
- Universidade Federal de Ciências da Saúde de Porto Alegre,
Programa de Pós-Graduação em Patologia, Porto Alegre, Rio Grande do Sul,
Brazil
- Irmandade da Santa Casa de Misericórdia de Porto Alegre,
Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, Rio
Grande do Sul, Brazil
| | - Pedro Enrico Ventura
- Irmandade da Santa Casa de Misericórdia de Porto Alegre,
Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, Rio
Grande do Sul, Brazil
| | - Roger Kist
- Irmandade da Santa Casa de Misericórdia de Porto Alegre,
Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, Rio
Grande do Sul, Brazil
| | - Valter Duro Garcia
- Irmandade da Santa Casa de Misericórdia de Porto Alegre,
Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, Rio
Grande do Sul, Brazil
| | - Gisele Meinerz
- Irmandade da Santa Casa de Misericórdia de Porto Alegre,
Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, Rio
Grande do Sul, Brazil
| | - Cristiane Valle Tovo
- Universidade Federal de Ciências da Saúde de Porto Alegre,
Departamento de Medicina Interna, Porto Alegre, Rio Grande do Sul, Brazil
| | - Guido Pio Cracco Cantisani
- Irmandade da Santa Casa de Misericórdia de Porto Alegre, Grupo
de Transplante Hepático, Porto Alegre, Rio Grande do Sul, Brazil
| | - Maria Lucia Zanotelli
- Irmandade da Santa Casa de Misericórdia de Porto Alegre, Grupo
de Transplante Hepático, Porto Alegre, Rio Grande do Sul, Brazil
| | - Marcos Mucenic
- Universidade Federal de Ciências da Saúde de Porto Alegre,
Programa de Pós-Graduação em Patologia, Porto Alegre, Rio Grande do Sul,
Brazil
- Irmandade da Santa Casa de Misericórdia de Porto Alegre, Grupo
de Transplante Hepático, Porto Alegre, Rio Grande do Sul, Brazil
| | - Elizete Keitel
- Universidade Federal de Ciências da Saúde de Porto Alegre,
Programa de Pós-Graduação em Patologia, Porto Alegre, Rio Grande do Sul,
Brazil
- Irmandade da Santa Casa de Misericórdia de Porto Alegre,
Departamento de Nefrologia e Transplante de Rim e Pâncreas, Porto Alegre, Rio
Grande do Sul, Brazil
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3
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Kosuta I, Ostojic A, Vujaklija Brajkovic A, Babel J, Simunov B, Sremac M, Mrzljak A. Shifting perspectives in liver diseases after kidney transplantation. World J Hepatol 2023; 15:883-896. [PMID: 37547033 PMCID: PMC10401415 DOI: 10.4254/wjh.v15.i7.883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/15/2023] [Accepted: 06/06/2023] [Indexed: 07/21/2023] Open
Abstract
Liver diseases after kidney transplantation range from mild biochemical abnormalities to severe hepatitis or cirrhosis. The causes are diverse and mainly associated with hepatotropic viruses, drug toxicity and metabolic disorders. Over the past decade, the aetiology of liver disease in kidney recipients has changed significantly. These relates to the use of direct-acting antiviral agents against hepatitis C virus, the increasing availability of vaccination against hepatitis B and a better understanding of drug-induced hepatotoxicity. In addition, the emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has brought new challenges to kidney recipients. This review aims to provide healthcare professionals with a comprehensive understanding of recent advances in the management of liver complications in kidney recipients and to enable them to make informed decisions regarding the risks and impact of liver disease in this population.
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Affiliation(s)
- Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia.
| | - Ana Ostojic
- Department of Gastroenterology and Hepatology, Liver Transplant Center, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Ana Vujaklija Brajkovic
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Jaksa Babel
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Bojana Simunov
- Department of Nephrology, University Hospital Merkur, Zagreb 10000, Croatia
| | - Maja Sremac
- Department of Gastroenterology and Hepatology, Liver Transplant Center, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, Liver Transplant Center, University Hospital Centre Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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4
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Schulz P, Wiginton A, Mahgoub A. Newly diagnosed hepatitis C infection after pancreas transplantation with multiple treatment failures. BMJ Case Rep 2023; 16:e254331. [PMID: 37137548 PMCID: PMC10163427 DOI: 10.1136/bcr-2022-254331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2023] [Indexed: 05/05/2023] Open
Abstract
This case represents the first report of a detected hepatitis C virus (HCV) infection following a pancreas transplantation that failed two different sofosbuvir (SOF)-based treatments. We present the case of a woman in her 30s with a history of kidney transplantation, who developed viremic symptoms 3 months after pancreas transplantation and with two subsequent negative HCV antibody tests. Further work-up revealed a positive HCV RNA test (genotype 1A, treatment naive). Two different direct-acting antiviral agents regimes with SOF failed in our case, and the patient achieved a sustained virological response with a 16-week course of glecaprevir/pibrentasvir.
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Affiliation(s)
- Philipp Schulz
- Internal Medicine, Texas Tech University Health Sciences Center School of Medicine Permian Basin, Odessa, Texas, USA
| | - Ashley Wiginton
- Transplant Hepatology and Gastroenterology, Baylor University Medical Center, Dallas, Texas, USA
| | - Amar Mahgoub
- Transplant Hepatology and Gastroenterology, Baylor University Medical Center, Dallas, Texas, USA
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5
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Jadoul M, Awan A, Berenguer M, Bruchfeld A, Fabrizi F, Goldberg D, Jia J, Kamar N, Mohamed R, Pessôa M, Pol S, Sise M, Martin P. KDIGO 2022 Clinical Practice Guideline FOR the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int 2022; 102:S129-S205. [PMID: 36410841 DOI: 10.1016/j.kint.2022.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/19/2022]
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Rendina M, Paoletti E, Labarile N, Marra A, Iannone A, Castellaneta A, Bussalino E, Ravera M, Schena A, Castellaneta NM, Barone M, Simone S, Gesualdo L, Di Leo A. HCV-positive kidney transplant patients treated with direct-acting antivirals maintain stable medium-term graft function despite persistent reduction in tacrolimus trough levels. Ther Adv Chronic Dis 2022; 13:20406223221117975. [PMID: 36147292 PMCID: PMC9486264 DOI: 10.1177/20406223221117975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 07/19/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND/AIM Direct-acting antivirals (DAAs) have improved the treatment of HCV-positive kidney transplant recipients (KTRs). However, their medium-term follow-up effects on graft function are conflicting. This study aimed to analyze how the interplay between DAAs, calcineurin inhibitors (CNI), and HCV eradication impacts 12-month kidney graft function. METHODS This double-center retrospective study with a prospective follow-up enrolled 35 KTRs with HCV treated with DAAs for 12 weeks. We compared three parameters: estimated glomerular filtration rate (eGFR), 24-h proteinuria, and CNI trough levels at three time points: baseline, end of treatment (EOT), and 12 months later. RESULTS Kidney allograft function remained stable when comparing baseline and 12-month post-treatment values of eGFR (60.7 versus 57.8 ml/min; p = 0.28) and 24-h proteinuria (0.3 versus 0.2 g/24 h; p = 0.15), while tacrolimus (Tac) trough levels underwent a statistically significant decline (6.9 versus 5.4 ng/ml; p = 0.004). Using an ongoing triple Tac-based maintenance therapy as a conservative measure, a dose escalation of Tac was applied only in seven patients. No variation in CyA and mTOR levels was detected. CONCLUSION DAA therapy is safe and effective in HCV-positive KTRs. It also produces a persistent significant reduction in Tac trough levels that does not influence graft function at 12 months.
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Affiliation(s)
- Maria Rendina
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | - Ernesto Paoletti
- Nephrology, Dialysis, and Transplantation,
University of Genova and Policlinico San Martino, Genova, Italy
| | - Nunzia Labarile
- Gastroenterology Unit, National Institute of
Gastroenterology IRCCS “Saverio de Bellis’, Research Hospital, Castellana
Grotte, 70013 Bari, Italy
| | - Antonella Marra
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | - Andrea Iannone
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | | | - Elisabetta Bussalino
- Nephrology, Dialysis, and Transplantation,
University of Genova and Policlinico San Martino, Genova, Italy
| | - Maura Ravera
- Nephrology, Dialysis, and Transplantation,
University of Genova and Policlinico San Martino, Genova, Italy
| | - Antonio Schena
- Nephrology, Dialysis and Transplantation,
University of Bari, Bari, Italy
| | | | - Michele Barone
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
| | - Simona Simone
- Nephrology, Dialysis and Transplantation,
University of Bari, Bari, Italy
| | - Loreto Gesualdo
- Nephrology, Dialysis and Transplantation,
University of Bari, Bari, Italy
| | - Alfredo Di Leo
- Gastroenterology and Digestive Endoscopy,
University Hospital, Bari, Italy
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7
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Utilization of HCV Viremic Kidneys with Genotyping/Subtyping-Free Sofosbuvir/Velpatasvir Treatment Strategy: Experience from China. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3758744. [PMID: 35941983 PMCID: PMC9356870 DOI: 10.1155/2022/3758744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Revised: 06/26/2022] [Accepted: 07/12/2022] [Indexed: 11/18/2022]
Abstract
Background. Owing to the advent of pangenotypic direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) treatment, utilization of HCV-infected deceased donor kidneys with simplified genotyping/subtyping-free sofosbuvir/velpatasvir (SOF/VEL) treatment strategy is now becoming a promising strategy for expanding the organ donor pool. Methods. This retrospective, comparative, single-center study included HCV viremic donor kidneys that were transplanted to 9 HCV-positive (HCV Ab-positive) recipients (D+/R+ group) and 14 HCV-negative recipients (D+/R- group) from May 2018 to January 2021. Both groups received prophylaxis with SOF/VEL treatment within 1-week posttransplant devoid of HCV genotyping/subtyping. The primary outcomes were sustained virologic response 12 weeks after completion of therapy (SVR12) and graft survival at 1-year posttransplant. Results. Baseline characteristics were similar between the HCV D+/R- and D+/R+ groups. The mean age of all recipients was
(SD) years, and 73.9% were male. A total of 92.9% (13 out of 14) recipients had pretreatment HCV viremia in the D+/R- group. The pretreatment HCV viral load in the D+/R+ group (5.98, log 10 IU/mL; IQR, 5.28-6.53) was significantly higher than that in the D+/R- group (3.61, log 10 IU/mL; IQR, 2.57-4.57). After SOF/VEL treatment, SVR12 was achieved in all recipients, with a 100% 1-year patient and graft survival rates. The D+/R+ group had a higher incidence of abnormal liver function (44.4% vs. 7.1%). No significant difference was observed between the two groups in terms of DGF, acute rejection, ALT, serum creatinine, and eGFR within 1-year posttransplant. No severe adverse events associated with either HCV viremia or SOF/VEL were observed. Conclusions. Using a simplified genotyping/subtyping-free SOF/VEL treatment strategy, kidneys from hepatitis C viremic donors for both infected and uninfected recipients presented with safe, excellent, and comparable 1-year outcomes, which can safely expand the donor pool. HCV-positive donor kidneys should be utilized regularly, regardless of the recipient’s HCV status.
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8
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Habas E, Farfar KL, Errayes N, Habas AM, Errayes M, Alfitori G, Rayani A, Elgara M, Al Adab AH, Elzouki A. Hepatitis Virus C-associated Nephropathy: A Review and Update. Cureus 2022; 14:e27322. [PMID: 36043014 PMCID: PMC9412079 DOI: 10.7759/cureus.27322] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2022] [Indexed: 11/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection causes hepatic and extrahepatic organ involvement. Chronic kidney disease (CKD) is a prevalent non-communicable disorder, accounting for significant morbidity and mortality worldwide. Acute kidney injury and CKD are not uncommon sequels of acute or chronic HCV infection. The pathogenesis of HCV-associated kidney injuries is not well explored. Excess cryoglobulin production occurs in HCV infection. The cryoglobulin may initiate immune complex-mediated vasculitis, inducing vascular thrombosis and inflammation due to cryoglobulin deposits. Furthermore, direct damage to nephron parts also occurs in HCV patients. Other contributory causes such as hypertension, diabetes, and genetic polymorphism enhance the risk of kidney damage in HCV-infected individuals. Implementing CKD prevention, regular evaluation, and therapy may improve the HCV burden of kidney damage and its related outcomes. Therefore, in this review, we discuss and update the possible mechanism(s) of kidney injury pathogenesis with HCV infection. We searched for related published articles in EMBASE, Google Scholar, Google, PubMed, and Scopus. We used various texts and phrases, including hepatitis virus and kidney, HCV and CKD, kidney pathology in viral hepatitis, kidney transplantation in HCV-infected patients, kidney allograft survival in viral hepatitis patients, mechanism of kidney pathology in viral hepatitis, dialysis and viral hepatitis, HCV infection and kidney injuries, and viral hepatitis and CKD progression, etc. to identify relevant articles.
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9
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Daloul R, Pesavento T, Goldberg DS, Reese PP. A review of kidney transplantation from HCV-viremic donors into HCV-negative recipients. Kidney Int 2021; 100:1190-1198. [PMID: 34237327 DOI: 10.1016/j.kint.2021.06.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/17/2021] [Accepted: 06/18/2021] [Indexed: 12/29/2022]
Abstract
The safety and efficacy of direct-acting antiviral therapies have allowed the transplantation of organs from hepatitis C virus (HCV)-viremic donors into uninfected recipients. This novel strategy contrasts with the previous standard-of-care practice of limiting the transplantation of HCV infected-donor organs to HCV-infected recipients, or all too often, discarding viable organs. In this review, we summarize the published literature about the safety and feasibility of transplanting organs from HCV-viremic donors, the challenges that hinder wider adoption of this strategy, and future research needs.
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Affiliation(s)
- Reem Daloul
- The Ohio State University Medical Center, Columbus, Ohio, USA.
| | - Todd Pesavento
- The Ohio State University Medical Center, Columbus, Ohio, USA
| | - David S Goldberg
- University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Peter P Reese
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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10
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL recommendations on treatment of hepatitis C: Final update of the series ☆. J Hepatol 2020; 73:1170-1218. [PMID: 32956768 DOI: 10.1016/j.jhep.2020.08.018] [Citation(s) in RCA: 748] [Impact Index Per Article: 149.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.
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Antithymocyte Globulin Versus Interleukin-2 Receptor Antagonist in Kidney Transplant Recipients With Hepatitis C Virus. Transplantation 2020; 104:1294-1303. [PMID: 32433232 DOI: 10.1097/tp.0000000000002959] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that antithymocyte globulin (ATG) might increase HCV-related complications. METHODS Using Scientific Registry of Transplant Recipients and Medicare claims data, we studied 6780 HCV+ and 139 681 HCV- KT recipients in 1999-2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (versus IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (versus IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression. RESULTS HCV+ recipients were less likely to receive ATG than HCV- recipients (living donor, adjusted odds ratio [aOR] = 0.640.770.91; deceased donor, aOR = 0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-y crude incidence = 11.6% versus 12.6%; aOR = 0.680.820.99). There was no significant difference in the risks of graft failure (adjusted hazard ratio [aHR] = 0.861.001.17), death (aHR = 0.850.951.07), liver transplant registration (aHR = 0.580.971.61), and cirrhosis (aHR = 0.730.921.16). CONCLUSIONS Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.
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12
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Association Between Serum Albumin Level and All-Cause Mortality in Patients With Chronic Kidney Disease: A Retrospective Cohort Study. Am J Med Sci 2020; 361:451-460. [PMID: 32958160 DOI: 10.1016/j.amjms.2020.07.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/17/2020] [Accepted: 07/15/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The association between serum albumin and all-cause mortality (ACM) in patients with chronic kidney disease (CKD) is presently unclear. METHODS The study subjects included 201 patients diagnosed with CKD, eliminating those with end-stage renal disease, who were admitted to our hospital from January 2014 to January 2015. The patients were divided into 4 groups according to serum albumin level (Q1: 1.60-3.88 g/dL; Q2: 3.89-4.13 g/dL; Q3: 4.14-4.43 g/dL, and Q4: 4.44-5.51 g/dL). The clinical outcome was ACM, and the difference was compared using odds ratio (OR) and 95% confidence interval (CI). RESULTS After a median follow-up of 1480 days, 32 patients died (15.92%). The ACM was found to be 28.00%, 20.00%, 8.00%, and 7.84% in the 4 groups (P = 0.012). Pearson correlation analysis revealed a positive association between the serum albumin level and glomerular filtration rate (GFR) (r = 0.22, P = 0.001). Once the potential confounding factors were adjusted, the results indicated that decreased serum albumin was a risk factor for ACM (Q2 vs Q1: OR = 0.50, 95% CI: 0.17-1.47; Q3 vs Q1: OR = 0.12, 95% CI: 0.03-0.48; Q4 vs Q1: OR = 0.26, 95% CI: 0.07-0.98). The receiver operating characteristic curve indicated that the optimum threshold of serum albumin to predict ACM was 4 g/dL, and the area under the curve was 0.69 (95% CI: 0.60-0.79). CONCLUSIONS Decreased serum albumin is a risk factor for ACM in patients with CKD, with the optimal threshold being 4 g/dL.
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13
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Hepatitis C in Chronic Kidney Disease: An Overview of the KDIGO Guideline. Clin Gastroenterol Hepatol 2020; 18:2158-2167. [PMID: 31376491 DOI: 10.1016/j.cgh.2019.07.050] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 07/11/2019] [Accepted: 07/29/2019] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection is a global health problem with significant health and economic burden, which can lead to chronic kidney disease (CKD) and affect multiple organ systems. In addition, prevalence of hepatitis C remains higher in patients with CKD, including those on chronic hemodialysis and in individuals with a kidney transplant than in the general population. There has been a dramatic shift in the management of hepatitis C since Kidney Disease: Improving Global Outcome (KDIGO) published its 2008 guideline for the prevention, diagnosis and management of hepatitis C in CKD. As a result, KDIGO published in 2018 an update to this guideline. In this narrative review, we present a synopsis of the guideline, including recommendations for screening and detection of HCV in CKD, treatment of HCV in patients with CKD, treatment of HCV before and after kidney transplantation, prevention of HCV transmission in hemodialysis units, and treatment of kidney disease related to HCV infection. We focus on the clinical aspects of using direct acting antivirals (DAAs) in patients with advanced CKD (G4 and G5), those on dialysis and kidney transplant recipients. We emphasize the importance of carefully managing drug-drug interactions between DAAs and immunosuppressive agents. We discuss timing of HCV treatment before vs. after kidney transplantation. Finally, we highlight areas of uncertainty where further research is needed before any definitive recommendations can be made.
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Kerollos KMN, El-Ameen HA, El Wahed LA, Azoz NMA. Prevalence and seroconversion of hepatitis C among hemodialysis patients in Assiut governorate, Egypt. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2020. [DOI: 10.1186/s43162-020-00005-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Abstract
Background
The prevalence of hepatitis C (HCV) infection among the patients on hemodialysis (HD) varies from country to country and from one center to another in the same country. Despite the existence of guidelines for the infection control program, Egypt is one of the countries with high HCV prevalence. In Egypt, the prevalence of HCV among hemodialysis patients in 2015 survey was 50.7%. This study aimed to evaluate the prevalence and seroconversion rate of hepatitis C infection and the risk factors for seroconversion in our community hemodialysis units.
Results
The prevalence of HCV was 34.8% among hemodialysis patients. The seroconversion rate was 13.2%. The positive history of blood transfusion and the frequency of blood transfusion, in addition to the handling by medical staff to equipment and blood products and the number of inserted temporary dialysis catheters, were found to be significant risk factors for seroconversion.
Conclusion
We concluded that there is a high prevalence of HCV infection in the dialysis units of our community and a relatively high seroconversion rate among hemodialysis patients.
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Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is associated with an increased incidence and progression of chronic kidney disease (CKD), as well as higher mortality in CKD and renal transplant patients. Direct acting antiviral agents (DAAs) have revolutionized the treatment of HCV, with viral eradication attained in 90-100% of treated patients. DAAs have an excellent safety and tolerability profile in CKD and renal transplant patients. AREAS COVERED In this review, we discuss the association of HCV with incidence and progression of CKD as well as its effect on outcomes and mortality. We also discuss the available treatment options in patients with CKD and renal transplant and in HCV-associated glomerular disease. EXPERT OPINION The availability of newly available direct acting anti-viral agents has revolutionized the treatment of HCV in persons with advanced CKD and undergoing dialysis. With these regimens, viral eradication can be attained in 90-100% of the treated patients. The safety, tolerability, and efficacy of these drugs in renal transplant patients have also made it possible to use HCV-infected grafts and successful virus eradication at a later stage.
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Affiliation(s)
- Muhammad Umair Khan
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Mohamed Ibrahim Mahmoud
- Department of Medicine, Division of Gastroenterology, Hamad Medical Corporation , Doha, Qatar
| | - Adeel A Butt
- Weill Cornell Medical College , New York, Qatar.,Department of Medicine, Hamad Medical Corporation , Doha, Qatar
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Kapila N, Menon KVN, Al-Khalloufi K, Vanatta JM, Murgas C, Reino D, Ebaid S, Shaw JJ, Agrawal N, Rhazouani S, Navas V, Sheffield C, Rahman AU, Castillo M, Lindenmeyer CC, Miller C, Quintini C, Zervos XB. Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience. Hepatology 2020; 72:32-41. [PMID: 31659775 DOI: 10.1002/hep.31011] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 10/22/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.
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Affiliation(s)
- Nikhil Kapila
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL.,Department of Gastroenterology and Hepatology, Duke University, Durham, NC
| | | | | | - Jason M Vanatta
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Carla Murgas
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Diego Reino
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Samer Ebaid
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Joshua J Shaw
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Neerja Agrawal
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Salwa Rhazouani
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Viviana Navas
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | | | - Asad Ur Rahman
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL
| | | | | | - Charles Miller
- Department of Transplant, Cleveland Clinic, Cleveland, OH
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Morales MK, Lambing T, Husson J. Review: Evaluation and Management of the HIV/HCV Co-Infected Kidney or Liver Transplant Candidate. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020. [DOI: 10.1007/s40506-020-00220-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Gaur N, Malhotra V, Agrawal D, Singh SK, Beniwal P, Sharma S, Jhorawat R, Rathore V, Joshi H. Sofosbuvir-Velpatasvir Fixed Drug Combination for the Treatment of Chronic Hepatitis C Infection in Patients With End-Stage Renal Disease and Kidney Transplantation. J Clin Exp Hepatol 2020; 10:189-193. [PMID: 32405174 PMCID: PMC7212294 DOI: 10.1016/j.jceh.2019.10.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION India is witnessing high hepatitis C virus (HCV) infection burden in patients of chronic kidney disease. Due to unavailability of costly Kidney Disease Improving Global Outcomes-recommended directly acting antiviral drugs, a widely available pan-genotypic combination of Sofosbuvir and Velpatasvir can become an economical option. Data regarding treatment experience of sofosbuvir-velpatasvir combination in chronic kidney disease is scarce. No data from India have been published in patients on renal replacement therapies till now. METHODS This retrospective analysis included all patients of end-stage renal disease on maintenance hemodialysis with treatment-naïve chronic HCV infection treated with sofosbuvir (400 mg) and velpatasvir (100 mg) fixed-dose combination. Pretreatment routine investigations were performed, which included HCV viral load, genotype, fibro scan, endoscopy for esophageal varices, and portal vein Doppler. The patients were followed up with HCV viral load to declare sustained virologic response. RESULT patients were included with a mean age of 39.8 ± 10.8 years, and 77.4% were male. Genotype 1 was found to be most prevalent (67.7%), with a median viral load of 106copies/ml. Six (19.3%) patients had hepatitis B virus co-infection. Three (9.7%) patients had cirrhosis. Sustained virologic response (SVR12) was achieved in 30 (96.8%) patients, and one (3.2%) patient had relapse. Furthermore, 14 (45.2%) patients underwent renal transplantation, and none of them had relapsed. Dyspepsia (9.7%) was the most common side effect observed with no major adverse effect. CONCLUSION Our study showed excellent efficacy with the safety profile of this drug combination in end-stage renal disease patients. However, larger prospective studies and multicenter randomized controlled trials are needed for further confirmation.
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Affiliation(s)
- Nisha Gaur
- SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Vinay Malhotra
- SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | | | | | - Pankaj Beniwal
- SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sanjeev Sharma
- SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | | | - Vinay Rathore
- SMS Medical College and Hospital, Jaipur, Rajasthan, India
| | - Harshal Joshi
- SMS Medical College and Hospital, Jaipur, Rajasthan, India
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Devresse A, Delire B, Lazarus JV, Kabamba B, De Meyer M, Mourad M, Buemi A, Darius T, Cambier JF, Goffin E, Jadoul M, Kanaan N. Eliminating Hepatitis C Virus From a Prevalent Kidney Transplant Recipient Population: A Single-Center Study in Belgium in the Direct-Acting Antivirals Era. Transplant Proc 2020; 52:815-822. [PMID: 32143864 DOI: 10.1016/j.transproceed.2020.01.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/10/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection. Although previous studies have reported positive results with DAAs after kidney transplantation (KT), their impact on the prevalence of HCV viremia (HCVv) in prevalent kidney transplant recipients (KTRs) remains ill defined. METHODS We retrospectively reviewed the HCV status of all patients followed at Cliniques Universitaires Saint-Luc, Brussels, Belgium, outpatient KT clinic between January 2014 and December 2018. We collected the clinical features of KTRs treated with DAAs during this period and calculated the annual prevalence of HCVv over this period. RESULTS Out of 1451 KTRs, 22 (1.52%) had HCVv in 2014 to 2018. From 2014 to 2018, the annual prevalence of HCVv dropped from 1.97% to 0.43%, (P < .001). Fourteen KTRs were treated with DAAs a median of 197 months (range: 5-374) after KT, mostly (79%) in 2017 after reimbursement restrictions of DAAs for KTRs in Belgium were removed. DAA treatment was safe with a sustained virological response rate at 12 weeks after treatment (SVR12) of 93%. Two patients died 14 months (lymphoma, despite SVR12) and 7 months (hepatocarcinoma, no SVR12) after DAAs initiation, respectively. Among HCVv KTRs not treated with DAAs (n = 8), 2 lost their graft, 5 died, and 1 is initiating therapy. The current prevalence of HCVv in the cohort is 0.08%, with a single patient currently on treatment. CONCLUSION Treatment with DAAs led to a dramatic decrease of HCVv prevalence in this KTR cohort. DAA use was safe and effective. Elimination of HCV is possible at KT clinics.
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Affiliation(s)
- Arnaud Devresse
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Bénédicte Delire
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Jeffrey V Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Barcelona, Spain
| | - Benoit Kabamba
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Department of Microbiology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Martine De Meyer
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Michel Mourad
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Antoine Buemi
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Tom Darius
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium; Department of Abdominal Surgery and Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Jean-François Cambier
- Department of Nephrology, Grand Hôpital de Charleroi (GHdC, site St-Joseph), Gilly, Belgium
| | - Eric Goffin
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Michel Jadoul
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Nada Kanaan
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
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Danış N, Toz H, Ünal N, Yılmaz M, Turan İ, Günşar F, Karasu Z, Ersöz G, Özkahya M, Akarca US. Paritaprevir, ritonavir, ombitasvir, and dasabuvir treatment in renal transplant patients with hepatitis C virus infection. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 30:695-701. [PMID: 31418413 DOI: 10.5152/tjg.2019.18833] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS The Social Security System of our country reimburses only paritaprevir, ritonavir, ombitasvir, and dasabuvir (PrOD) regime in treatment-naive patients with hepatitis C regardless of kidney disease. Most of our renal transplant (RT) recipients were treated with PrOD. The aim of the present study was to investigate the efficacy and safety of PrOD in RT patients with hepatitis C virus (HCV) infection in a single center real-life experience. MATERIALS AND METHODS RT recipients with a post-transplant follow-up of at least 1 year were included in the study. The patients were treated and monitored according to the guidelines. Blood levels of immunosuppressive patients were closely followed up and adjusted. RESULTS A total of 21 (12 male and nine female) patients were assessed. The age of the patients was 50.8±8.5 years. Ten patients were infected with G1a, 10 patients with G1b, and one patient with G4 HCV. Two patients had compensated cirrhosis. Eighteen patients were treatment-naive, and three were peginterferon+ribavirin-experienced. Sustained virologic response (SVR12) was achieved in all patients. None of the patients discontinued the treatment. Cyclosporine (Csa) and tacrolimus (Tac) doses were reduced to once a day to once a week to maintain the blood level within normal range. The most common adverse effect was anemia in patients receiving ribavirin. Renal functions did not change during the treatment period. CONCLUSION In this real-life experience, all of the 21 PrOD-treated RT recipients reached SVR12. Tac or Csa serum levels were maintained within the normal range with close monitoring. PrOD regime can be successfully and safely used in RT recipients with HCV infection with close follow-up.
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Affiliation(s)
- Nilay Danış
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Hüseyin Toz
- Department of Nephrology, Ege University School of Medicine, İzmir, Turkey
| | - Nalan Ünal
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Mümtaz Yılmaz
- Department of Nephrology, Ege University School of Medicine, İzmir, Turkey
| | - İlker Turan
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Fulya Günşar
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Zeki Karasu
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Galip Ersöz
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
| | - Mehmet Özkahya
- Department of Nephrology, Ege University School of Medicine, İzmir, Turkey
| | - Ulus Salih Akarca
- Department of Gastroenterology, Ege University School of Medicine, İzmir, Turkey
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Yuan Q, Hong S, Perez-Ortiz A, Roth E, Chang DC, Madsen JC, Elias N. Effect of Recipient Hepatitis C Status on Outcomes of Deceased Donor Kidney Transplantation. J Am Coll Surg 2020; 230:853-861.e3. [PMID: 32035979 DOI: 10.1016/j.jamcollsurg.2019.12.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 12/30/2019] [Indexed: 11/18/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection has been deemed detrimental to kidney transplantation (KT) outcomes. Breakthrough HCV treatment with direct-acting antiviral (DAA) medications improved the probability of HCV+ kidney use for KT even in noninfected (HCV-) recipients. We hypothesized that recipient HCV infection influences deceased donor KT outcomes, and this effect could be modified by donor HCV status and use of DAAs. STUDY DESIGN We conducted a retrospective cohort study based on data from the Organ Procurement and Transplantation Network as of September 2018. A mate kidneys analysis was performed with HCV+ and HCV- recipients of solitary adult KT from ABO-compatible deceased donor between January 1994 and June 2018. We selected donors where 1 KT recipient was HCV+ and the mate kidney recipient was HCV-. Both HCV- and HCV+ donors were identified and analyzed separately. Outcomes, including survival of patients, grafts, and death-censored grafts, were compared between the groups. RESULTS Four-hundred and twenty-five HCV+ and 5,575 HCV- donor mate kidneys were transplanted in HCV-discrepant recipients. HCV+ recipients of HCV- donor had worse patient and graft survival (adjusted hazard ratio 1.28; 95% CI, 1.19 to 1.37 and adjusted hazard ratio 1.26; 95% CI 1.18 to 1.34, respectively) and death-censored grafts (adjusted hazard ratio 1.24; 95% CI, 1.15 to 1.34) compared with HCV- recipients. Comparable patient and graft survival and death-censored grafts were found in recipients of HCV+ donors, regardless of recipient HCV status. The risk associated with HCV positivity in donors or recipients in the pre-DAA era (before December 2013) was no longer statistically significant in the post-DAA era. CONCLUSIONS Given comparable outcomes between HCV+ and HCV- recipients in post-DAA era or when receiving HCV+ donor kidneys, broader use of HCV+ kidneys regardless of the recipient's HCV status should be advocated, and allocation algorithm for HCV+ kidneys should be revised.
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Affiliation(s)
- Qing Yuan
- Transplant Center, Massachusetts General Hospital, Boston, MA; Organ Transplant Institute, 8th Medical Center, Chinese PLA General Hospital, Beijing, China; Harvard Medical School, Boston, MA
| | - Shanjuan Hong
- Transplant Center, Massachusetts General Hospital, Boston, MA
| | | | - Eve Roth
- Transplant Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA
| | - David C Chang
- Harvard Medical School, Boston, MA; Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Joren C Madsen
- Transplant Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA; Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Nahel Elias
- Transplant Center, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA; Department of Surgery, Massachusetts General Hospital, Boston, MA; Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA.
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Wu SH, Loong CC, Chu CJ, Su CW, Lin CC, Hsia CY, Liu C, Lee SD, Wang YJ, Lee FY, Linb NC, Chen CY, Huang YH, Hou MC. Highly effective treatment response and well tolerability by all oral direct acting antivirals for chronic hepatitis C patients post organ transplantation. J Chin Med Assoc 2020; 83:18-24. [PMID: 31714442 DOI: 10.1097/jcma.0000000000000222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immunosuppressant-related acceleration of fibrosis has been documented in chronic hepatitis C (CHC) patients who receive organ transplantation (Tx), and sustained virological response (SVR) rates for these patients by pegylated interferon (IFN)-based therapy are generally poor and associated with unfavorable safety profiles. In addition, IFN treatment varies by patient and poses a high risk of post-renal Tx graft rejection. This study was aimed to investigate the efficacy and safety of all oral direct acting antivirals (DAAs) for CHC patients following organ Tx. METHODS A total of 32 organ Tx (liver: 17, kidney: 13, kidney then liver: 1, and heart: 1) patients with CHC on an oral DAA (paritaprevir/ritonavir, ombitasvir, and dasabuvir: 11, daclatasvir and asunaprevir: 4, sofosbuvir-based: 17) were enrolled in the study. DAAs regimen was based by genotype/subtype, patient characteristics, drug interaction profiles, and health insurance coverage. RESULTS Mean patient age was 61.4 ± 9.5 years, 50.0% male, and 15.6% with cirrhosis. Fourteen (43.7%) patients experienced unsuccessful IFN treatment. Genotype distribution was as follows: 1a: 6, 1b: 17, 2: 7, 3: 1, and 6: 1. Mean time between Tx and DAAs therapy was 77.3 ± 11.0 months. Baseline HCV RNA before DAAs was 6.20 ± 0.19 log10 IU/mL. After DAAs, the distribution of week 2 HCV RNA was as follows: <15 IU/mL (53.1%), 15 to 50 IU/mL (15.6%), 50 to 100 IU/mL (6.3%), and >100 IU/mL (25.0%), respectively. The rates of undetectable HCV RNA (<15 IU/mL) at week 4 and end-of-treatment were 93.8% and 100%, respectively. Subjective adverse events during therapy were generally mild, with no treatment terminations. After posttreatment follow-up, all 32 patients (100%) achieved SVR12. CONCLUSION Highly responsive treatment and favorable tolerability were achieved by all oral DAAs in this difficult-to-treat patient population.
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Affiliation(s)
- Sih-Hsien Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chi-Jen Chu
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chung-Chi Lin
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yuan Hsia
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chinsu Liu
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shou-Dong Lee
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC
| | - Yuan-Jen Wang
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Niang-Cheng Linb
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Cheng-Yen Chen
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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Gandhi TS, Natarajan G, Jayachandran D, Thanigachalam D, Ramanathan S, Alavudeen S. Direct-acting antivirals in the treatment of hepatitis C virus infection in renal transplant recipients: A single-center experience from South India. INDIAN JOURNAL OF TRANSPLANTATION 2020. [DOI: 10.4103/ijot.ijot_46_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Radhakrishnan RC, Gopal B, Zachariah UG, Abraham P, Mohapatra A, Valson AT, Alexander S, Jacob S, Tulsidas KS, David VG, Varughese S. The long-term impact of hepatitis C infection in kidney transplantation in the pre-direct acting antiviral era. SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2019; 29:1092-1099. [PMID: 30381505 DOI: 10.4103/1319-2442.243964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs.
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Affiliation(s)
| | - Basu Gopal
- Central Northern Adelaide Renal and Transplant Service, Royal Adelaide Hospital, Adelaide, Australia
| | - Uday G Zachariah
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Priya Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Anjali Mohapatra
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Anna T Valson
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Shibu Jacob
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Vinoi G David
- Department of Nephrology, Christian Medical College, Vellore, India
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25
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Maghrabi HME, Elmowafy AY, Refaie AF, Elbasiony MA, Shiha GE, Rostaing L, Bakr MA. Efficacy and safety of the new antiviral agents for the treatment of hepatitis C virus infection in Egyptian renal transplant recipients. Int Urol Nephrol 2019; 51:2295-2304. [PMID: 31531807 DOI: 10.1007/s11255-019-02272-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 08/28/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) is common and can impact on patient and graft survival rates. The efficacy and safety of direct-acting antivirals (DAAs) to treat genotype-4 HCV-infected KTRs have not been fully established. METHODS A prospective, single-arm, single-center study was conducted at Mansoura Urology/Nephrology Center (Mansoura University, Egypt). 114 HCV RNA(+) genotype 4 KTRs were enrolled in this study after a hepatology consultation and consented to start treatment with interferon-free DAAs. A sofosbuvir-based regimen was given to 109 recipients that had creatinine clearance (Crcl) of > 30 mL/min/1.73 m2. Ritonavir-boosted paritaprevir/ombitasvir was prescribed to five recipients with Crcl < 30 mL/min/1.73 m2. RESULTS The mean age of the cohort was 45.2 ± 11.2 years; most were male. The mean duration with a transplant was 14.2 ± 3.5 years, with different immunosuppressive regimens, mostly based on calcineurin inhibitors. A rapid virological response (RVR), i.e., clearance of viral load, was achieved in 100% at 4 weeks after starting treatment. All patients had a sustained virological response (SVR) at 12 and 24 weeks posttreatment, with one exception. During DAA therapy serum creatinine increased in 12 patients. In three, this was concomitant with elevated calcineurin inhibitor and sirolimus trough levels. Graft biopsies were performed in 8 of these 12 patients: these revealed an acute rejection in 4 cases (acute cellular rejection grade-1A: n = 2, and grade-1B: n = 2). The rejection episodes occurred at 4-6 weeks after starting treatment. CONCLUSION DAAs were highly efficacious and safely treated genotype-4 HCV-infected KTRs and had no significant adverse effects on graft function/survival.
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Affiliation(s)
- Hanzada Mohamed El Maghrabi
- Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.,Nephrology Department, Port-Said University, Port Said, Egypt
| | | | | | - Mohammed Adel Elbasiony
- Egyptian Liver research Institute and Hospital, Mansoura, Egypt.,Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | | | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, CHU Grenoble-Alpes, CS 10217, 38043, Grenoble Cedex 09, France.
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26
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Liyanage L, Muzaale AD, Henderson ML, Durand CM. Living kidney donation in individuals with hepatitis C and HIV infection: rationale and emerging evidence. CURRENT TRANSPLANTATION REPORTS 2019; 6:167-176. [PMID: 32855901 PMCID: PMC7449146 DOI: 10.1007/s40472-019-00242-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
PURPOSE OF REVIEW HIV-infected (HIV+) and hepatitis C virus-infected (HCV+) individuals with end-stage renal disease (ESRD) have decreased access to kidney transplantation. With new opportunities provided by the HIV Organ Policy Equity (HOPE) Act and direct-acting antivirals (DAAs) for HCV, we explore the potential risks and benefits of living donor kidney transplantation from HIV+ or HCV+ donors, from the perspective of both donor health and recipient outcomes. RECENT FINDINGS The HOPE Act permits organ donation from both deceased and living HIV+ persons to HIV+ recipients; however, there is only clinical experience with HIV+ deceased donors to date. Empirical evidence demonstrates a low but acceptable risk of ESRD in potential HIV+ living donors without comorbidities who have well-controlled infection in the absence of donation. With the availability of potent DAAs for eradication of HCV infection, growing evidence shows good outcomes with HCV seropositive and/or viremic deceased kidney donors, providing rationale to consider HCV+ living donors. SUMMARY HIV+ and HCV+ living donor kidney transplantation may improve access to transplant for vulnerable ESRD populations. Careful evaluation and monitoring are warranted to mitigate potential risks to donors and recipients.
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Affiliation(s)
- Luckmini Liyanage
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Abimereki D. Muzaale
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Macey L. Henderson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Christine M. Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
- Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
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27
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Sise ME, Strohbehn IA, Bethea E, Gustafson JL, Chung RT. Balancing the risk and rewards of utilizing organs from hepatitis C viremic donors. Curr Opin Organ Transplant 2019; 24:351-357. [PMID: 31090648 PMCID: PMC7093034 DOI: 10.1097/mot.0000000000000651] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW Owing to long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of hepatitis C viremic-deceased donor organs are under investigation in kidney, liver, heart, and lung transplantation. RECENT FINDINGS Direct-acting antiviral medications for hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early posttransplant direct-acting antiviral therapy, 100% of uninfected recipients of hepatitis C viremic organs have been cured of infection after transplantation. SUMMARY In this manuscript, we review the risks and rewards of utilizing hepatitis C viremic organs for transplantation.
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Affiliation(s)
- Meghan E. Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital
| | - Ian A. Strohbehn
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Emily Bethea
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Jenna L. Gustafson
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Raymond T. Chung
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
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28
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Fabrizi F, Dixit V, Messa P. Hepatitis C virus and mortality among patients on dialysis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2019; 43:244-254. [PMID: 30910601 DOI: 10.1016/j.clinre.2018.10.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 10/08/2018] [Accepted: 10/15/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND RATIONALE The role of hepatitis C virus (HCV) as an independent risk factor for death in dialysis population is unclear. DESIGN A systematic review of the published medical literature was performed to evaluate the impact of positive anti-HCV serologic status on all-cause and disease-specific mortality in patients on regular dialysis. The risk of all-cause, cardiovascular and liver disease-related mortality was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for mortality with HCV across the published studies. RESULTS Twenty-three observational studies (n = 574,081 patients on long-term dialysis) were identified. Pooling of study results demonstrated that HCV positive status was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted death risk (all-cause mortality) with HCV was 1.26 (95% CI: 1.18; 1.34) (P < 0.0001). Between-study heterogeneity was found (Q value 52.8, P = 0.001). The overall estimate for adjusted death risk (liver disease-related mortality) was 5.05 (95% CI: 2.53; 10.0) (P < 0.0001); heterogeneity statistics, Q value 8.2, P = 0.04. The overall estimate for adjusted death risk (cardiovascular mortality) was 1.18 (95% CI: 1.085; 1.29) (P < 0.0001) (no heterogeneity). Meta-regression showed that the effect of HCV on all-cause mortality was more evident in those studies provided with a greater size (P = 0.0001), a higher prevalence of diabetics (P = 0.0005) and HCV-infected individuals (P = 0.001). CONCLUSIONS An association between HCV positive serologic status and increased risk of either liver or cardiovascular disease-related mortality exists among dialysis patients.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy.
| | - Vivek Dixit
- Division of Gastroenterology, UCLA School of Medicine, Los Angeles, CA, USA
| | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy; University School of Medicine, Milano, Italy
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29
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Reddy YNV, Nunes D, Chitalia V, Gordon CE, Francis JM. Hepatitis C virus infection in kidney transplantation-changing paradigms with novel agents. Hemodial Int 2019; 22 Suppl 1:S53-S60. [PMID: 29694721 DOI: 10.1111/hdi.12659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha-based therapies that were difficult to tolerate and were associated with adverse side-effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side-effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon-based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct-acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation.
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Affiliation(s)
- Yuvaram N V Reddy
- Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA
| | - David Nunes
- Division of Gastroenterology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Vipul Chitalia
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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30
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Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int 2019; 22 Suppl 1:S61-S70. [PMID: 29694723 DOI: 10.1111/hdi.12643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus (HCV) infection is prevalent in patients with kidney disease including transplant candidates and recipients. It is associated with increased morbidity and mortality in end-stage renal disease patients and also increases the risk of allograft rejection and decreases allograft and patient survival post-transplant. Newly developed direct acting antivirals have revolutionized the way HCV is treated. Whether patients are treated before or after kidney transplantation, the cure rates with direct acting antivirals are >90%. Great debate has formed revolving the optimal timing to treat kidney transplant candidates. On the one hand, treatment before transplantation decreases early post-transplant complications related to HCV. On the other, postponing treatment until after transplantation opens the possibility of transplanting a kidney from a HCV positive donor, which is associated with shorter waiting time and improved organ utilization by expanding the organ donor pool. Most patients living in an area where waiting time is reduced by accepting an HCV positive kidney would benefit by the strategy of treatment post-transplantation, but this decision needs to be individualized in a patient-by-patient basis given that there are special circumstances (i.e., severe HCV-related extrahepatic manifestations, availability of live donors, etc.) in which treatment before transplant might be preferred.
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Affiliation(s)
- Abraham Cohen-Bucay
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA.,Division of Nephrology and Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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31
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Sise ME, Chute DF, Gustafson JL, Wojciechowski D, Elias N, Chung RT, Williams WW. Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients. Hemodial Int 2019; 22 Suppl 1:S71-S80. [PMID: 29694722 DOI: 10.1111/hdi.12650] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Long wait times for kidney transplant and the high risk of mortality on dialysis have prompted investigation into strategies to increase organ allocation and decrease discard rates of potentially viable kidneys. Organs from hepatitis C virus (HCV) antibody positive donors are often rejected; nearly 500 HCV-infected kidneys are discarded annually in the United States. Due the opioid epidemic, the number of HCV-infected donors has increased because of a rise in both new HCV infections and drug-related deaths. In the past 5 years, HCV has been transformed into a curable illness with direct-acting antiviral therapies (DAAs) that are effective in >95% of patients treated and are extremely well tolerated. Recent data has shown several direct-acting antiviral combinations are safe and effective after kidney transplant, and can achieve the same high cure rate seen in the general population and without increasing the rate of acute rejection. Because of this, strategies to decrease discard of HCV-infected organs have been devised. Two recent studies have transplanted HCV-uninfected dialysis patients with kidneys from donors actively infected with HCV; recipients were treated with DAA in the peri-transplant period. More research is needed to determine the safety and efficacy of this approach, but it has the potential to dramatically increase the donor pool of available kidneys, shorten waitlist times and ultimately decreases mortality in patients waiting for kidney transplant.
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Affiliation(s)
- Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Donald F Chute
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jenna L Gustafson
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - David Wojciechowski
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nahel Elias
- Department of Transplant Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Winfred W Williams
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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32
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Del Bello A, Abravanel F, Alric L, Lavayssiere L, Lhomme S, Bellière J, Izopet J, Kamar N. No evidence of occult hepatitis C or E virus infections in liver-transplant patients with sustained virological response after therapy with direct acting agents. Transpl Infect Dis 2019; 21:e13093. [PMID: 30972874 DOI: 10.1111/tid.13093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 02/21/2019] [Accepted: 04/07/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS It has been recently suggested that occult hepatitis C virus (HCV) infection and hepatitis E virus (HEV) reactivation might occur after direct acting antiviral agent-induced (DAA-induced) sustained virological response (SVR). The aim of our study was to identify occult HCV and HEV infection in a cohort of organ transplant patients who had achieved SVR and had persistent elevation in liver-enzyme levels. PATIENTS AND METHOD Sixty-six liver and/or kidney transplant patients were treated with DAAs. All but one achieved SVR12. Twenty-nine (8-39) months post-SVR12, 8 of the 65 patients (12.3%) who achieved SVR12 had persistently elevated liver enzyme levels. In 1 patient, this was related to hepatitis B virus reactivation. In the 7 remaining patients, blood samples (n = 7), liver biopsies (n = 4), and peripheral blood mononuclear cells (PBMCs) (n = 7) were collected simultaneously in order to identify occult HCV or HEV infection. RESULTS Hepatitis C virus RNA and HEV RNA were not detected in serum, liver tissues, or PBMCs. No HEV reactivation was observed after HCV clearance in patients who had anti-HEV IgG. CONCLUSION Our study suggests that there is no occult HCV or HEV infection in transplant patients after successful treatment of HCV infection with DAAs, even in patients with a persistent elevation of liver enzyme levels. However, due to the small number of patients included in our study, this finding should be confirmed in a larger cohort.
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Affiliation(s)
- Arnaud Del Bello
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Florence Abravanel
- Department of Virology, Institut Fédératif de Biologie de Purpan, CHU Toulouse, France.,Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
| | - Laurent Alric
- Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152 Pharma Dev, IRD Toulouse 3 University, Toulouse, France
| | - Laurence Lavayssiere
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
| | - Sébastien Lhomme
- Department of Virology, Institut Fédératif de Biologie de Purpan, CHU Toulouse, France.,Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
| | - Julie Bellière
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,Université Paul Sabatier, Toulouse, France
| | - Jacques Izopet
- Department of Virology, Institut Fédératif de Biologie de Purpan, CHU Toulouse, France.,Centre de Physiopathologie de Toulouse Purpan, CHU Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
| | - Nassim Kamar
- Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.,Université Paul Sabatier, Toulouse, France.,INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
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33
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Armando C, Evangelista S, Massimiliano C, Silvia A, Gaia P, Paola I, Maria C, Gianluca M, Nicola C, Concetta Anna D, Massimo C, Caterina S. Eradication of HCV Infection with the Direct-Acting Antiviral Therapy in Renal Allograft Recipients. BIOMED RESEARCH INTERNATIONAL 2019; 2019:4674560. [PMID: 31179323 PMCID: PMC6507153 DOI: 10.1155/2019/4674560] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 01/14/2019] [Accepted: 03/26/2019] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) infection unfavorably affects the survival of both renal patients undergoing hemodialysis and renal transplant recipients. In this subset of patients, the effectiveness and safety of different combinations of interferon-free direct-acting antiviral agents (DAAs) have been analyzed in several small studies. Despite fragmentary, the available data demonstrate that DAA treatment is safe and effective in eradicating HCV infection, with a sustained virologic response (SVR) rates nearly 95% and without an increased risk of allograft rejection. This review article analyzes the results of most published studies on this topic to favor more in-depth knowledge of the readers on the subject. We suggest, however, perseverating in this update as the optimal DAA regimen may not be proposed yet, because of the expected arrival of newer DAAs and of the lack of data from large multicenter randomized controlled trials.
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Affiliation(s)
- Calogero Armando
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Sagnelli Evangelista
- Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Creta Massimiliano
- Department of Neurosciences, Human Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy
| | - Angeletti Silvia
- Unit of Clinical Laboratory Science, University Campus Bio-Medico of Rome, Rome, Italy
| | - Peluso Gaia
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Incollingo Paola
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Candida Maria
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Minieri Gianluca
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Carlomagno Nicola
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Dodaro Concetta Anna
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Ciccozzi Massimo
- Unit of Medical Statistic and Molecular Epidemiology, University Campus Bio-Medico, Rome, Italy
| | - Sagnelli Caterina
- Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
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34
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Camargo JF, Anjan S, Chin-Beckford N, Morris MI, Abbo LM, Simkins J, Ciancio G, Chen LJ, Burke GW, Figueiro J, Guerra G, Kupin WL, Mattiazzi A, Ortigosa-Goggins M, Ram Bhamidimarri K, Roth D. Clinical outcomes in HIV+/HCV+ coinfected kidney transplant recipients in the pre- and post-direct-acting antiviral therapy eras: 10-Year single center experience. Clin Transplant 2019; 33:e13532. [PMID: 30866102 DOI: 10.1111/ctr.13532] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 03/02/2019] [Accepted: 03/08/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Previous studies have demonstrated inferior patient and graft survival following kidney transplant (KT) in HIV+/HCV+ coinfected patients compared to HIV+/HCV- recipients. However, these studies were conducted prior to the availability of direct-acting antiviral (DAA) agents and data in the modern era are lacking. METHODS Single center retrospective study of HIV+/HCV+ coinfected KT recipients (2007-2017). Outcomes were assessed for the pre-DAA and post-DAA (ie, after December 2013) eras including 1-year patient survival, death-censored graft survival, and acute rejection; and serious infections (defined as infections requiring admission to the intensive care unit during initial transplant hospitalization or re-admission to the hospital after discharge) within the first 6 months post-transplant. RESULTS A total of 13 consecutive HIV+/HCV+ recipients were identified. Median time of post-transplant follow-up was 722 days. Seven patients were transplanted in the DAA era; five of them had anti-HCV Ab+ donors, with two donors being HCV NAT positive; all received DAA therapy, six of them post-transplant (median time from KT to DAA: 83 days; IQR, 54-300). All the patients in the pre-DAA era were on a protease inhibitor-containing ART regimen. One-year patient and death-censored graft survivals were 83% and 67%, respectively, for the patients transplanted in the pre-DAA era, and 100% for both outcomes in the subgroup of patients transplanted in the post-DAA era (P > 0.05). Compared to patients in the post-DAA era, those in the pre-DAA era had higher incidence of serious infections (0 vs 67%; P = 0.02). Acute rejection exclusively occurred in the pre-DAA group (n = 1; 17%). CONCLUSIONS Outcomes of HIV+/HCV+ KT recipients, including HIV-/HCV+ to HIV+/HCV+ transplants, in the DAA era were excellent in this small cohort. Larger studies are needed.
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Affiliation(s)
- Jose F Camargo
- Division of Infectious Disease, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Shweta Anjan
- Division of Infectious Disease, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | | | - Michele I Morris
- Division of Infectious Disease, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Lilian M Abbo
- Division of Infectious Disease, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Jacques Simkins
- Division of Infectious Disease, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Gaetano Ciancio
- Department of Surgery, University of Miami Miller School of Medicine, and Miami Transplant Institute, Miami, Florida
| | - Linda J Chen
- Department of Surgery, University of Miami Miller School of Medicine, and Miami Transplant Institute, Miami, Florida
| | - George W Burke
- Department of Surgery, University of Miami Miller School of Medicine, and Miami Transplant Institute, Miami, Florida
| | - Jose Figueiro
- Department of Surgery, University of Miami Miller School of Medicine, and Miami Transplant Institute, Miami, Florida
| | - Giselle Guerra
- Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Warren L Kupin
- Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Adela Mattiazzi
- Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Mariella Ortigosa-Goggins
- Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - Kalyan Ram Bhamidimarri
- Division of Hepatology, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
| | - David Roth
- Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine Miami, Florida
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Esforzado N, Morales JM. Hepatitis C and kidney transplant: The eradication time of the virus has arrived. Nefrologia 2019; 39:458-472. [PMID: 30905391 DOI: 10.1016/j.nefro.2019.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 01/07/2019] [Accepted: 01/13/2019] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a factor that reduces the survival of the patient and the graft in renal transplant (RT). The availability of directly acting antivirals agents (DAAs), very effective and with an excellent safety profile, it allows eradicate HCV from patients with kidney disease, and this is a revolutionary radical change in the natural evolution of this infection, until now without effective and safe treatment for the contraindication use of interferon in kidney transplant patients. The efficiency of some DAAs for all genotypes, even in patients with renal insufficiency constitutes a huge contribution to eradicate HCV in the RT population independently the genotype, severity of kidney failure, progression of liver disease and previous anti HCV therapy. All this is raising, although with controversies, the possibility of use kidneys from infected HCV+ donors for transplant in uninfected receptors and can be treated successfully in the early post-TR, thus increasing the total "pool" of kidneys for RT.
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Abstract
Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.
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Affiliation(s)
- Abraham Cohen-Bucay
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.,Nephrology Department, American British Cowdray Medical Center, Mexico City, 05300, Mexico
| | - Craig E Gordon
- Division of Nephrology, Tufts Medical Center, Boston, MA, 02111, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, MA, 02118, USA
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Gendia M, Lampertico P, Alfieri CM, D'Ambrosio R, Gandolfo MT, Campise MR, Fabrizi F, Messa P. Impact of hepatitis C virus and direct acting antivirals on kidney recipients: a retrospective study. Transpl Int 2019; 32:493-501. [PMID: 30580473 DOI: 10.1111/tri.13393] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 05/22/2018] [Accepted: 12/17/2018] [Indexed: 01/07/2023]
Abstract
Hepatitis C virus (HCV) in kidney transplanted patients (KTx-p) carries a high risk for a worse outcome. This retrospective study evaluates the impact of HCV and of the new direct acting antivirals (DAAs) on patient and graft outcomes in KTx patients. Forty (6.5%) of the 616 KTx-p, who received a kidney transplantation (KTx) in our Centre had antibodies against HCV: 13 were positive for HCV RNA and received DAAs (Group A); 11 were HCV RNA positive and did not receive any treatment (Group B; n = 11); 16 were negative for HCV RNA (Group C). All Group A patients had HCV RNA negativity after 12 weeks of treatment, and 12 (92.30%) achieved a sustained virological response (SVR). Only two patients, who had proteinuria greater than 500 mg/day showed a worsening of proteinuria after antiviral therapy in Group A. Liver enzyme elevation and death were significantly more frequent in Group B than other groups. Our results support the notion that active HCV infection negatively affects kidney recipients and that DAA have a high safety and efficacy profile after KTx with no significant negative effect on allograft function, particularly in well-functioning renal grafts.
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Affiliation(s)
- Mohamed Gendia
- Unit of Nephrology, Dialysis and Renal Transplant, Department of Medicine, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy.,Nephrology Unit, Internal Medicine Department, Zagazig University, Zagazig, Egypt
| | - Pietro Lampertico
- CRC "A. M.e A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.,Università degli studi di Milano, Milan, Italy
| | - Carlo Maria Alfieri
- Unit of Nephrology, Dialysis and Renal Transplant, Department of Medicine, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Roberta D'Ambrosio
- CRC "A. M.e A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
| | - Maria Teresa Gandolfo
- Unit of Nephrology, Dialysis and Renal Transplant, Department of Medicine, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Maria Rosaria Campise
- Unit of Nephrology, Dialysis and Renal Transplant, Department of Medicine, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Fabrizio Fabrizi
- Unit of Nephrology, Dialysis and Renal Transplant, Department of Medicine, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy
| | - Piergiorgio Messa
- Unit of Nephrology, Dialysis and Renal Transplant, Department of Medicine, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milan, Italy.,Università degli studi di Milano, Milan, Italy
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Wong T, Bloom RD. Management and treatment of the HCV-infected kidney transplant patient. Semin Dial 2018; 32:169-178. [PMID: 30536995 DOI: 10.1111/sdi.12766] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The prevalence of hepatitis C virus infection is increased in patients with end stage kidney disease compared to the general population and is an adverse outcome determinant. Direct-acting antiviral therapy for hepatitis C virus is changing the management paradigm of infected kidney transplant candidates and recipients, with potential to reduce patient morbidity and mortality. This review describes the hepatic and nonhepatic manifestations of hepatitis C virus in kidney transplant patients as well as management and treatment strategies to optimize transplant outcomes, highlighting the importance of direct-acting antivirals in this population.
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Affiliation(s)
- Tiffany Wong
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Roy D Bloom
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Fabrizi F, Messa P. The epidemiology of HCV infection in patients with advanced CKD/ESRD: A global perspective. Semin Dial 2018; 32:93-98. [PMID: 30536715 DOI: 10.1111/sdi.12757] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver disease in patients with chronic kidney disease (CKD) is most commonly due to hepatitis C virus (HCV) and contributes to increased rates of mortality. Among the pre-dialysis population, the estimated prevalence of anti-HCV positivity is based on few, limited-size studies. In hemodialysis patients however, HCV remains very prevalent despite large declines in seropositivity rates in dialysis facilities in developed countries after preventive measures were adopted in the 1990s. Recent surveys indicate that the HCV seropositivity prevalence ranges from 1.4%-28.3%, and 4.7%-41.9%, among maintenance dialysis patients in developed and developing countries respectively. Although the full extent of dialysis unit-associated HCV transmission is unknown, outbreaks continue to occur, regardless of health system infrastucture. According to US Centers for Disease Control data, over 50% of health care-associated HCVoutbreaks reported from 2008 to 2015 occurred within dialysis facilities. Strict adherence to infection control procedures and routine serologic screening plays a pivotal role in preventing transmission of HCV within hemodialysis units, even in the setting of low HCV prevalence. With the advent of directly acting antivirals, cure of HCV-infected patients on maintenance hemodialysis will help reduce transmission within units and further lower the frequency of HCV infection.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milan, Italy
| | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milan, Italy.,University School of Medicine, Milan, Italy
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40
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Henson JB, Sise ME. The association of hepatitis C infection with the onset of CKD and progression into ESRD. Semin Dial 2018; 32:108-118. [PMID: 30496620 DOI: 10.1111/sdi.12759] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infection is not only an important cause of chronic liver disease, but extrahepatic manifestations are common and include chronic kidney disease (CKD). HCV is classically associated with cryoglobulinemic glomerulonephritis in the context of mixed cryoglobulinemia syndrome, but other glomerular diseases also occur and may be significantly under-recognized. HCV may cause glomerular disease by immune complex deposition; however, other potential mechanisms by which HCV promotes CKD include a direct cytopathic effect of the virus on renal tissue, and by its association with accelerated atherosclerosis, insulin resistance, and chronic inflammation. Epidemiologic studies show HCV infection confers an increased risk of incident CKD and accelerates progression of CKD to end-stage renal disease (ESRD) in the general population, as well as subpopulations including diabetic patients, those coinfected with human immunodeficiency virus (HIV), and kidney transplant recipients. Patients with CKD and HCV infection experience inferior clinical outcomes, including poorer quality of life and an increased risk of mortality. Treatment with interferon-based regimens is associated with decreased risk of incident CKD and ESRD, though prior studies are limited by the small number of patients with HCV and CKD who underwent treatment. With the advent of new, well-tolerated direct-acting antiviral combinations that are not cleared by the kidneys, it is possible to treat all genotypes of HCV infection in patients with CKD and ESRD. More data on the effect of direct-acting antivirals on CKD incidence and progression are necessary. However, there is every expectation that with improved access to HCV treatment, the burden of CKD in patients with HCV could significantly decline.
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Affiliation(s)
- Jacqueline B Henson
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
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41
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Goldberg D, Reese PP. Risks, benefits, and ethical questions associated with transplanting kidneys from hepatitis C virus-infected donors into hepatitis C virus-negative patients. Semin Dial 2018; 32:179-186. [DOI: 10.1111/sdi.12767] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- David Goldberg
- Division of Gastroenterology, Department of Medicine; University of Pennsylvania; Philadelphia Pennsylvania
- Department of Biostatistics, Epidemiology, and Informatics; University of Pennsylvania; Philadelphia Pennsylvania
| | - Peter P. Reese
- Department of Biostatistics, Epidemiology, and Informatics; University of Pennsylvania; Philadelphia Pennsylvania
- Division of Renal, Electrolyte, and Hypertension; University of Pennsylvania; Philadelphia Pennsylvania
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43
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KDIGO 2018 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. Kidney Int Suppl (2011) 2018; 8:91-165. [PMID: 30675443 PMCID: PMC6336217 DOI: 10.1016/j.kisu.2018.06.001] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Eradication of HCV in Renal Transplant Recipients and Its Effects on Quality of Life. BIOMED RESEARCH INTERNATIONAL 2018; 2018:8953581. [PMID: 30246027 PMCID: PMC6136566 DOI: 10.1155/2018/8953581] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 08/14/2018] [Indexed: 02/08/2023]
Abstract
Background The use of direct antiviral agents (DAA) has radically modified the course of HCV hepatitis in renal patients. Aim of this study was to assess the effects of HCV eradication on quality of life (QOL) in renal transplant recipients (RTR), measured by CLDQ and SF-36. Methods Sixteen RTR with well preserved GFR (mean: 60.3±19.3 ml/min) and chronic HCV infection with moderate liver stiffness (9.3±1.7 kPa) were given a sofosbuvir-based regimen for 12 weeks and had a 1 year follow-up. Results At end of treatment (EOT) a complete viral clearance was observed in all the patients, with normalization of most laboratory data and a consistent reduction in liver stiffness. All these parameters remained stable after 1 year, as well as renal function and proteinuria. Questionnaire data showed consistent amelioration in different “emotional” domains at EOT, which persisted after 1 year and were associated with a globally improved QOL, although there was no change in most of the “physical” domains in both questionnaires. One patient under ribavirin developed an acute anemia and withdrew from the study, but no further adverse episode was observed throughout the study. Conclusions Our data, while confirming the efficacy of oral DAA, show that HCV infection represents a heavy psychological burden in renal transplant recipients, greatly alleviated by viral eradication, which determines a significant improvement in QOL that represents an important outcome in management of all transplant recipients. This trial is registered with ISRCTN97560076.
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45
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Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol 2018; 69:461-511. [PMID: 29650333 DOI: 10.1016/j.jhep.2018.03.026] [Citation(s) in RCA: 1205] [Impact Index Per Article: 172.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Zaky Z, Augustine JJ. Hepatitis C treatment in kidney transplant recipients: the need for sustained vigilance after sustained viral response. Transpl Int 2018; 31:867-869. [PMID: 29480973 DOI: 10.1111/tri.13143] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 02/21/2018] [Indexed: 12/28/2022]
Affiliation(s)
- Ziad Zaky
- Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH, USA
| | - Joshua J Augustine
- Department of Nephrology and Hypertension, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
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47
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The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2018. [DOI: 10.1016/j.rgmxen.2017.11.002] [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: 12/09/2022] Open
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48
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Kim SM, Song IH. Hepatitis C virus infection in chronic kidney disease: paradigm shift in management. Korean J Intern Med 2018; 33:670-678. [PMID: 29961309 PMCID: PMC6030406 DOI: 10.3904/kjim.2018.202] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Accepted: 06/17/2018] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events. CKD patients with HCV infection require antiviral therapy. Pegylated interferon (peg-IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV agents. Peg-IFN-based treatment has a low virologic response rate and poor compliance, resulting in a high dropout rate. Recently, several clinical trials of all-DAA combination regimens have reported excellent antiviral efficacy and few adverse drug reactions in HCV-infected patients with CKD. These positive results have revolutionized the treatment of chronic HCV infection in this population. In this review, we address the impact of chronic HCV infection in CKD patients, and discuss their management using next-generation DAAs.
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Affiliation(s)
- So Mi Kim
- Division of Nephrology, Department of Internal Medicine, Dankook University Hospital, Cheonan, Korea
| | - Il Han Song
- Division of Hepatology, Department of Internal Medicine, Dankook University Hospital, Cheonan, Korea
- Correspondence to Il Han Song, M.D. Division of Hepatology, Department of Internal Medicine, Dankook University Hospital, 201 Manghyang-ro, Dongnam-gu, Cheonan 31116, Korea Tel: +82-41-5503924 Fax: +82-41-5563256 E-mail:
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Aiza-Haddad I, Ballesteros-Amozurrutia A, Borjas-Almaguer OD, Castillo-Barradas M, Castro-Narro G, Chávez-Tapia N, Chirino-Sprung RA, Cisneros-Garza L, Dehesa-Violante M, Flores-Calderón J, Flores-Gaxiola A, García-Juárez I, González-Huezo MS, González-Moreno EI, Higuera-de la Tijera F, Kershenobich-Stalnikowitz D, López-Méndez E, Malé-Velázquez R, Marín-López E, Mata-Marín JA, Méndez-Sánchez N, Monreal-Robles R, Moreno-Alcántar R, Muñoz-Espinosa L, Navarro-Alvarez S, Pavia-Ruz N, Pérez-Ríos AM, Poo-Ramírez JL, Rizo-Robles MT, Sánchez-Ávila JF, Sandoval-Salas R, Torre A, Torres-Ibarra R, Trejo-Estrada R, Velarde-Ruiz Velasco JA, Wolpert-Barraza E, Bosques-Padilla F. The Mexican consensus on the treatment of hepatitis C. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2018; 83:275-324. [PMID: 29803325 DOI: 10.1016/j.rgmx.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 10/17/2017] [Accepted: 11/02/2017] [Indexed: 12/12/2022]
Abstract
The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.
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Affiliation(s)
| | | | - O D Borjas-Almaguer
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - G Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - L Cisneros-Garza
- Centro de Enfermedades Hepáticas del Hospital San José, Monterrey, Nuevo León, México
| | | | - J Flores-Calderón
- Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Ciudad de México, México
| | | | - I García-Juárez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - E I González-Moreno
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | | | - E López-Méndez
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática, Guadalajara, Jalisco, México
| | | | - J A Mata-Marín
- Hospital de Infectología del Centro Médico Nacional «La Raza», Ciudad de México, México
| | | | - R Monreal-Robles
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - L Muñoz-Espinosa
- Hospital Universitario «Dr. José Eleuterio González», Monterrey, Nuevo León, México
| | | | - N Pavia-Ruz
- Hospital Infantil de México «Federico Gómez», Ciudad de México, México
| | - A M Pérez-Ríos
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | - J L Poo-Ramírez
- Clínica San Jerónimo de Salud Hepática y Digestiva, Ciudad de México, México
| | | | - J F Sánchez-Ávila
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - A Torre
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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Denewar AA, Abbas MH, Sheashaa HA, Abdelaal I, El-Dahshan K, Matter YE, Refaie AF. Detection of Hepatis C Virus-Related Immunologic Markers and Their Impact on Outcomes of Living-Donor Kidney Transplant Recipients. EXP CLIN TRANSPLANT 2018; 17:79-83. [PMID: 29957163 DOI: 10.6002/ect.2017.0161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Liver disease is an important cause of morbidity and mortality among recipients of transplanted organs. In addition to the liver, hepatitis C virus infection has a significant prevalence among recipients of kidney transplant and is related to worse graft and recipient survival as the kidney is an important component of the hepatitis C virus clinical syndrome. MATERIALS AND METHODS This retrospective single center study included 336 patients with end-stage renal disease who received a kidney transplant at the Mansoura Urology and Nephrology Center from January 1992 to December 1995. Of 336 patients, 63 were excluded, and the remaining 273 patients were divided into 3 groups: viremic active (72 patients), viremic inactive (108 patients), and nonviremic (93 patients). Division of patients was based on hepatitis C virus RNA complement level (C3 and/or C4 consumption), circulating cryoglobulins, and rheumatoid factor detection. RESULTS Our study showed insignificant differences regarding patient characteristics and demographic data among the study groups but significantly higher incidence of transaminitis in viremic (active and inactive) patients. Nonsignificant differences were found regarding proteinuria among the 3 groups, including among those who had levels in either nephrotic or nonnephrotic ranges. Biopsy-proven acute rejection episodes among the 3 groups of recipients were statistically comparable, with significantly higher frequency of chronic rejection episodes among viremic active patients. Nonviremic recipients had significantly lower serum creatinine levels than viremic (active and inactive) recipients. Patient and graft survival results were comparable among the groups. CONCLUSIONS Presence of hepatitis C virus immunologic markers does not have a significant effect on patient and graft survival; however, it may be a clue for long-term incidence of chronic rejection.
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Affiliation(s)
- Ahmed Abdelfattah Denewar
- From the Department of Dialysis and Transplantation, The Urology-Nephrology Center, Mansoura University, Mansoura, Egypt
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