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Kizilbash SJ, Evans MD, Smith J, Engen RM. The landscape of hepatitis C virus infection in pediatric kidney transplantation. Am J Transplant 2025; 25:1235-1244. [PMID: 39862906 DOI: 10.1016/j.ajt.2025.01.030] [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: 05/27/2024] [Revised: 01/09/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025]
Abstract
Hepatitis C virus (HCV) infection is increasing in prevalence due to the growing opioid epidemic; however, its impact on pediatric kidney transplantation is unknown. This study compared kidney transplant outcomes between HCV-positive and propensity score-weighted HCV-negative pediatric recipients. It also examined HCV-positive kidney utilization for pediatric transplantation in the United States. We used the Scientific Registry of Transplant Recipients to identify pediatric kidney transplants (aged < 18 years) performed between April 1, 1994 and December 1, 2022. We used propensity score weighting to create a group of HCV-negative recipients with characteristics similar to HCV-positive recipients. Odds ratios for delayed graft function and hazard ratio (HR) for patient and graft survival were estimated using logistic and Cox regression models. We found similar delayed graft function rates (13.9% vs 10.3%, P = .14) and no difference in the graft (HR: 1.04, 95% CI: 0.83-1.31, P = .71; 10-year survival 54.9% vs 54.5%) or patient survival (HR: 1.06, 95% CI: 0.58-1.95, P = .84; 10-year survival 93.9% vs 92.0%) between the groups. Four HCV-positive (2.5%), 3 HCV-negative children (0.02%), and 1 (0.05%) child with unknown HCV status received HCV-positive kidneys. We observed no increased risk of graft loss or death in children with HCV infection. The use of HCV-positive donors for pediatric kidney transplantation is rare.
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Affiliation(s)
- Sarah J Kizilbash
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
| | - Michael D Evans
- Department of Biostatistics, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minnesota, USA
| | - Jodi Smith
- Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington, USA
| | - Rachel M Engen
- Department of Pediatrics, University of Wisconsin Madison, Madison, Wisconsin, USA
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2
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Yuan Q, Hong S, Leya G, Roth E, Tsoulfas G, Williams WW, Madsen JC, Elias N. Analysis of the effects of donor and recipient hepatitis C infection on kidney transplant outcomes in the United States. World J Transplant 2023; 13:44-57. [PMID: 36908306 PMCID: PMC9993188 DOI: 10.5500/wjt.v13.i2.44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 11/07/2022] [Accepted: 12/21/2022] [Indexed: 02/16/2023] Open
Abstract
BACKGROUND As Hepatitis C virus infection (HCV+) rates in kidney donors and transplant recipients rise, direct-acting antivirals (DAA) may affect outcomes. AIM To analyze the effects of HCV+ in donors, recipients, or both, on deceased-donor (DD) kidney transplantation (KT) outcomes, and the impact of DAAs on those effects. METHODS The Organ Procurement and Transplantation Network data of adult first solitary DD-KT recipients 1994-2019 were allocated into four groups by donor and recipient HCV+ status. We performed patient survival (PS) and death-censored graft survival (DCGS) pairwise comparisons after propensity score matching to assess the effects of HCV+ in donors and/or recipients, stratifying our study by DAA era to evaluate potential effect modification. RESULTS Pre-DAA, for HCV+ recipients, receiving an HCV+ kidney was associated with 1.28-fold higher mortality (HR 1.151.281.42) and 1.22-fold higher death-censored graft failure (HR 1.081.221.39) compared to receiving an HCV- kidney and the absolute risk difference was 3.3% (95%CI: 1.8%-4.7%) for PS and 3.1% (95%CI: 1.2%-5%) for DCGS at 3 years. The HCV dual-infection (donor plus recipient) group had worse PS (0.56-fold) and DCGS (0.71-fold) than the dual-uninfected. Donor HCV+ derived worse post-transplant outcomes than recipient HCV+ (PS 0.36-fold, DCGS 0.34-fold). In the DAA era, the risk associated with HCV+ in donors and/or recipients was no longer statistically significant, except for impaired PS in the dual-infected vs dual-uninfected (0.43-fold). CONCLUSION Prior to DAA introduction, donor HCV+ negatively influenced kidney transplant outcomes in all recipients, while recipient infection only relatively impaired outcomes for uninfected donors. These adverse effects disappeared with the introduction of DAA.
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Affiliation(s)
- Qing Yuan
- Department of Urology, Chinese PLA General Hospital, Beijing 100853, China
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Shanjuan Hong
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Gregory Leya
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Eve Roth
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Georgios Tsoulfas
- Department of Surgery, Aristototle University of Thessaloniki, Thessaloniki 541 24, Greece
| | - WW Williams
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
- Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Joren C Madsen
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
- Division of Cardiac Surgery, Massachusetts General Hospital, Boston, MA 02114, United States
| | - Nahel Elias
- Transplant Center and Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA 02114, United States
- Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA 02114, United States
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3
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Sawinski D, Rosenblatt RE, Morales JM. Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years' experience. Nefrologia 2022:S2013-2514(22)00178-X. [PMID: 36564226 DOI: 10.1016/j.nefroe.2022.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 04/18/2022] [Indexed: 06/17/2023] Open
Abstract
Kidney transplantation is the optimal therapy for end-stage kidney disease but limited by the available number of organs. Using HCV+ donors, both in HCV+ and HCV- recipients, is a rational response to the organ shortage. We review the historic experience using HCV+ donors in HCV+ recipients and assess long-term results. We also discuss contemporary practices, including the transplantation of HCV-viremic kidneys into HCV- recipients with different approaches to posttransplant HCV therapy.
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Affiliation(s)
- Deirdre Sawinski
- Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
| | - Russel E Rosenblatt
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA
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Shadekejiang H, Zhu J, Wu X. Transplant of Kidneys From Hepatitis C Virus-Positive Donors To Hepatitis C Virus-Negative Recipients: A Retrospective Study and Systematic Review. EXP CLIN TRANSPLANT 2022; 20:1076-1084. [PMID: 36718006 DOI: 10.6002/ect.2022.0315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
OBJECTIVES Kidneys from hepatitis C virus-positive donors were often discarded due to the lack of an effective treatment for hepatitis C virus. However, the advent of direct-acting antivirals has facilitated great progress for treatment of hepatitis C virus, providing additional opportunities for patients waiting for kidney transplant. We explored the feasibility and safety of kidney transplant from hepatitis C virus- positive donors to hepatitis C virus-negative recipients in combination with direct-acting antiviral therapy. MATERIALS AND METHODS This was a single-center retrospective study of 7 recipients of hepatitis C virus- positive kidneys from June 2018 to June 2021. All recipients were treated with sofosbuvir/velpatasvir for 12 weeks after kidney transplant. The primary recipients' outcome was achievement of sustained viral eradication at 12 weeks after treatment, and follow-up secondary outcomes were kidney function recovery, liver function, and adverse drug reactions. We reviewed previous studies, from 2017 to 2022, to analyze achievement of sustained viral eradication at 12 weeks after treatment, recipient and graft survival, and adverse event of kidney transplant from a hepatitis C virus-positive donor to a hepatitis C virus-negative recipient. RESULTS Median follow-up time was 71 weeks (range, 56-183 weeks). All recipients achieved sustained viral eradication at 12 weeks after treatment, and their kidney function recovered without severe liver damage or adverse drug reactions. Previous studies suggested that transplant of hepatitis C virus-positive donor kidneys is safe and feasible when combined with direct-acting antiviral therapy. However, details regarding optimal duration of treatment and directacting antiviral regimen remain undetermined, so prospective randomized studies are warranted. CONCLUSIONS Our study further confirms that kidney transplant from hepatitis C virus-positive donors to hepatitis C virus-negative recipients is safe and feasible with direct-acting antiviral treatment. Grafts from hepatitis C virus-infected donors may be effective to resolve the problem of kidney shortage.
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Affiliation(s)
- Halinuer Shadekejiang
- From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
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5
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Sawinski D, Rosenblatt RE, Morales JM. Renal transplantation using kidneys from hepatitis C-infected donors: A review of 30-years’ experience. Nefrologia 2022. [DOI: 10.1016/j.nefro.2022.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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6
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El Helou G, Jay C, Nunez M. Hepatitis C virus and kidney transplantation: Recent trends and paradigm shifts. Transplant Rev (Orlando) 2022; 36:100677. [DOI: 10.1016/j.trre.2021.100677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 12/28/2021] [Accepted: 12/31/2021] [Indexed: 12/09/2022]
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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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8
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Impact of Donor Hepatitis C Virus on Kidney Transplant Outcomes for Hepatitis C-positive Recipients in the Direct-acting Antiviral Era: Time to Revise the Kidney Donor Risk Index? Transplantation 2020; 104:1215-1228. [PMID: 31517783 DOI: 10.1097/tp.0000000000002949] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Kidneys from donors with hepatitis C virus (HCV) infection are traditionally considered to be at risk for poorer survival outcomes, as reflected in the kidney donor profile index (KDPI). Modern direct-acting antivirals may modify this risk. METHODS Using United Network for Organ Sharing data, HCV-infected adult first-time kidney transplant recipients from 2014 to 2017 were examined. Graft and patient survival were compared in a propensity-matched cohort of recipients of HCV antibody (Ab)(+) kidneys versus Ab(-) kidneys. Subsequent analysis was performed in a propensity-matched cohort of recipients of HCV-viremic (RNA positive) versus HCV-naïve kidneys. RESULTS There were 379 recipients each in the matched cohort of recipients of HCV Ab(+) versus HCV Ab(-) kidneys. Despite a higher KDPI (58.2% for HCV Ab[+] versus 38.8% for HCV Ab[-]), 1-year patient and graft survival were similar in the HCV(+) and HCV(-) groups (95.4% and 94.9% versus 97.9% and 96.0%, P = 0.543 and P = 0.834, respectively). There were 200 recipients each in the cohort of recipients of HCV-viremic versus HCV-naïve kidneys, with the KDPI again higher in the HCV-viremic group (56.8% versus 35.2%). Baseline hazard ratios (HRs) for graft failure (HR, 4.69; P = 0.009) and death (HR, 7.60; P = 0.003) were significantly elevated in the viremic group, but crossed 1 at 21 and 24 months, respectively. CONCLUSIONS In the modern direct-acting antiviral era, calculated likely KDPI overestimates risk kidneys from HCV (+) donors. Donor viremia conveys an early risk which appears to subside over time. These results suggest that it may be time to revise the kidney donor risk index.
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Said A, Weiss M, Varhelyi A, Farago R, Ballweg C, Rice J, Agarwal P, Fernandez L, Foley D. Utilization of hepatitis C viremic donors for liver transplant recipients without hepatitis C. A veterans transplant center report. Transpl Infect Dis 2020; 23:e13466. [PMID: 32931616 DOI: 10.1111/tid.13466] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 08/24/2020] [Accepted: 09/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND We report our experience utilizing liver donors with HCV Viremia (RNA+) for HCV-negative recipients (HCV D+R-) at a Veterans Affairs (VA) transplant center. METHODS In 2018, we introduced an informed consent process for HCV D+R- liver transplants. RESULTS Eight HCV D+R- liver transplants (LT) were performed. Median time from listing to LT was 189 days (range 41-511). Median MELD at LT was 23.5 (median MELD at LT of 31 for center). All recipients developed HCV viremia after transplant. Median time to DAA initiation was 10 days after viremia (range 3-25). After transplant, the DAAs used were Mavyret in five recipients and Epclusa in three, all for 12 weeks. All eight patients completed DAA therapy and achieved negative HCV RNA by end of therapy (ETR) and seven reached sustained virologic response (SVR) by 12 weeks after end of therapy. One patient died from chronic ischemic encephalopathy after ETR, before SVR. CONCLUSIONS HCV D+R- is a practical strategy to expand the pool of donor organs. It shortened waiting time, allowing patients to receive transplants at lower MELD scores. VA liver transplant programs have provided universal and timely access to post-transplant HCV DAA therapy after donor-derived infection.
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Affiliation(s)
- Adnan Said
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - Matthew Weiss
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - Anna Varhelyi
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - Rebecca Farago
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - Cristy Ballweg
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - John Rice
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - Parul Agarwal
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - Luis Fernandez
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
| | - David Foley
- University of Wisconsin School of Medicine and Public Health and William S Middleton, VA Medical Center, Madison, WI, USA
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10
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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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11
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van Riet RC, van Dijk KM, van den Hoogen MWF. New possibilities on transplanting kidneys from hepatitis C virus positive donors: a Systematic Review. Transplant Rev (Orlando) 2020; 34:100532. [PMID: 31948862 DOI: 10.1016/j.trre.2020.100532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 11/17/2019] [Accepted: 12/18/2019] [Indexed: 01/16/2023]
Affiliation(s)
- Renske C van Riet
- Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam.
| | - Kiki M van Dijk
- Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam.
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12
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Morales JM, Sawinski D. New insights into the rational use of HCV+ organs worldwide. Clin Transplant 2019; 33:e13739. [PMID: 31648391 DOI: 10.1111/ctr.13739] [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: 08/19/2019] [Revised: 10/08/2019] [Accepted: 10/15/2019] [Indexed: 01/06/2023]
Abstract
Hepatitis C (HCV) is a worldwide health problem. Effective therapies for HCV infection, coupled with an increase in deceased donors due to the opioid epidemic, have led to the broader availability and the use of HCV-infected donor organs, including HCV nucleic acid test-positive (NAT+) donors in HCV-negative recipients. In this review, we discuss the prevalence of HCV infection, trends in the use of HCV-infected donors, and outcomes for those who receive HCV-seropositive or HCV NAT+ donor organs. We discuss management considerations such as hepatitis B reactivation, selection of the optimal direct-acting antiviral regimen, and potential complications. We also present a framework for the rational use of HCV-infected donor organs in the future.
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Affiliation(s)
- Jose M Morales
- Research Institute, Hospital 12 de Octubre, Complutense University, Madrid, Spain
| | - Deirdre Sawinski
- Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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13
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Sawinski D, Forde KA, Lo Re V, Goldberg DS, Cohen JB, Locke JE, Bloom RD, Brensinger C, Weldon J, Shults J, Reese PP. Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study. Am J Kidney Dis 2019; 73:815-826. [PMID: 30704882 DOI: 10.1053/j.ajkd.2018.11.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 11/20/2018] [Indexed: 12/25/2022]
Abstract
RATIONALE & OBJECTIVE Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. EXPOSURE HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. OUTCOMES Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. ANALYTICAL APPROACH After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. RESULTS Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. LIMITATIONS No data for HCV viral load or liver biopsy. CONCLUSIONS HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.
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Affiliation(s)
- Deirdre Sawinski
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Kimberly A Forde
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Vincent Lo Re
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - David S Goldberg
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Jordana B Cohen
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Jayme E Locke
- Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, AL
| | - Roy D Bloom
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Colleen Brensinger
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Joe Weldon
- DaVita Clinical Research, Minneapolis, MN; Children's Hospital of Philadelphia, Philadelphia, PA
| | - Justine Shults
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; DaVita Clinical Research, Minneapolis, MN; Children's Hospital of Philadelphia, Philadelphia, PA
| | - Peter P Reese
- Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
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14
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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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15
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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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Reese PP, Abt PL, Blumberg EA, Van Deerlin VM, Bloom RD, Potluri VS, Levine M, Porrett P, Sawinski D, Nazarian SM, Naji A, Hasz R, Suplee L, Trofe-Clark J, Sicilia A, McCauley M, Gentile C, Smith J, Niknam BA, Bleicher M, Reddy KR, Goldberg DS. Twelve-Month Outcomes After Transplant of Hepatitis C-Infected Kidneys Into Uninfected Recipients: A Single-Group Trial. Ann Intern Med 2018; 169:273-281. [PMID: 30083748 DOI: 10.7326/m18-0749] [Citation(s) in RCA: 175] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Organs from hepatitis C virus (HCV)-infected deceased donors are often discarded. Preliminary data from 2 small trials, including THINKER-1 (Transplanting Hepatitis C kidneys Into Negative KidnEy Recipients), suggested that HCV-infected kidneys could be safely transplanted into HCV-negative patients. However, intermediate-term data on quality of life and renal function are needed to counsel patients about risk. OBJECTIVE To describe 12-month HCV treatment outcomes, estimated glomerular filtration rate (eGFR), and quality of life for the 10 kidney recipients in THINKER-1 and 6-month data on 10 additional recipients. DESIGN Open-label, nonrandomized trial. (ClinicalTrials.gov: NCT02743897). SETTING Single center. PARTICIPANTS 20 HCV-negative transplant candidates. INTERVENTION Participants underwent transplant with kidneys infected with genotype 1 HCV and received elbasvir-grazoprevir on posttransplant day 3. MEASUREMENTS The primary outcome was HCV cure. Exploratory outcomes included 1) RAND-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) quality-of-life scores at enrollment and after transplant, and 2) posttransplant renal function, which was compared in a 1:5 matched sample with recipients of HCV-negative kidneys. RESULTS The mean age of THINKER participants was 56.3 years (SD, 6.7), 70% were male, and 40% were black. All 20 participants achieved HCV cure. Hepatic and renal complications were transient or were successfully managed. Mean PCS and MCS quality-of-life scores decreased at 4 weeks; PCS scores then increased above pretransplant values, whereas MCS scores returned to baseline values. Estimated GFRs were similar between THINKER participants and matched recipients of HCV-negative kidneys at 6 months (median, 67.5 vs. 66.2 mL/min/1.73 m2; 95% CI for between-group difference, -4.2 to 7.5 mL/min/1.73 m2) and 12 months (median, 72.8 vs. 67.2 mL/min/1.73 m2; CI for between-group difference, -7.2 to 9.8 mL/min/1.73 m2). LIMITATION Small trial. CONCLUSION Twenty HCV-negative recipients of HCV-infected kidneys experienced HCV cure, good quality of life, and excellent renal function. Kidneys from HCV-infected donors may be a valuable transplant resource. PRIMARY FUNDING SOURCE Merck.
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Affiliation(s)
- Peter P Reese
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Peter L Abt
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Emily A Blumberg
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Vivianna M Van Deerlin
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Roy D Bloom
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Vishnu S Potluri
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Matthew Levine
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Paige Porrett
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Deirdre Sawinski
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Susanna M Nazarian
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Ali Naji
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Richard Hasz
- Gift of Life Donor Program, Philadelphia, Pennsylvania (R.H., L.S.)
| | - Lawrence Suplee
- Gift of Life Donor Program, Philadelphia, Pennsylvania (R.H., L.S.)
| | - Jennifer Trofe-Clark
- Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.T.)
| | - Anna Sicilia
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Maureen McCauley
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - Caren Gentile
- University of Pennsylvania Health System, Philadelphia, Pennsylvania (C.G., J.S.)
| | - Jennifer Smith
- University of Pennsylvania Health System, Philadelphia, Pennsylvania (C.G., J.S.)
| | - Bijan A Niknam
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (B.A.N.)
| | - Melissa Bleicher
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - K Rajender Reddy
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
| | - David S Goldberg
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (P.P.R., P.L.A., E.A.B., V.M.V., R.D.B., V.S.P., M.L., P.P., D.S., S.M.N., A.N., A.S., M.M., M.B., K.R.R., D.S.G.)
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17
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Sageshima J, Troppmann C, McVicar JP, Santhanakrishnan C, de Mattos AM, Perez RV. Impact of Willingness to Accept Hepatitis C Seropositive Kidneys Among Hepatitis C RNA-Positive Waitlisted Patients. Transplantation 2018; 102:1179-1187. [PMID: 29953423 PMCID: PMC7228641 DOI: 10.1097/tp.0000000000002096] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/14/2017] [Accepted: 11/28/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Kidney transplantation from hepatitis C seropositive (HCV+) donors may benefit hepatitis C RNA-positive (RNA+) candidates, but it is unclear how the willingness to be listed for and accept such kidneys affects waitlist and transplant outcomes. METHODS In a single-center retrospective analysis, HCV+ transplant candidates (N = 169) listed from March 2004 to February 2015 were evaluated. All RNA+ candidates were offered the option to be listed for HCV+ donors. RNA- candidates were listed only for HCV- donors. RESULTS Fifty-seven patients (51% of all RNA+ transplant candidates) willing to accept HCV+ donors were listed for both HCV+ and HCV- donor kidneys. During 6-year follow up, 43 (75%) of 57 patients accepting HCV+ versus 19 (35%) of 55 patients not accepting HCV+ received a deceased donor kidney transplant (P < 0.0001). Multivariable analysis demonstrated that willingness to be listed for and accept HCV+ kidneys was associated with receiving deceased donor kidney transplant (P = 0.0016). Fewer patients accepting HCV+ donors (7 [12%] vs 16 [29%]) were removed from the list due to death or deteriorated medical condition (P = 0.0117). Posttransplant patient and graft survival rates were not significantly different. Overall patient survival since the listing (combined waitlist and posttransplant survival) was similar among the groups. CONCLUSIONS HCV RNA+ candidates had better access to transplantation and similar overall survival before the era of widespread use of direct-acting anti-HCV agents.
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Affiliation(s)
| | | | - John P McVicar
- Department of Surgery, University of California Davis, Sacramento, CA
| | | | - Angelo M de Mattos
- Department of Internal Medicine, University of California Davis, Sacramento, CA
| | - Richard V Perez
- Department of Surgery, University of California Davis, Sacramento, CA
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18
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Li Vecchi M, La Spada E, Li Vecchi V, Montalto G. Hepatitis C Virus Infection in Hemodialyzed Patients. Int J Artif Organs 2018; 30:100-7. [PMID: 17377904 DOI: 10.1177/039139880703000204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in non-infected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders. Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.
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Affiliation(s)
- M Li Vecchi
- Department of Nephrology, University of Palermo, Palermo, Italy
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19
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Kasarala G, Choi S, Lopez K, Britt RB, Boatright C, Tillmann HL. Curing hepatitis C virus (HCV) after organ transplantation: Increased risk of rejection following HCV elimination. Transpl Infect Dis 2017; 20. [PMID: 29064152 DOI: 10.1111/tid.12796] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Revised: 06/21/2017] [Accepted: 06/30/2017] [Indexed: 11/26/2022]
Affiliation(s)
- George Kasarala
- Division of Gastroenterology, Department of Medicine, East Carolina University, Greenville, NC, USA
| | - Steve Choi
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC, USA.,Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Katie Lopez
- Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Rachel B Britt
- Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Colleen Boatright
- Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Hans L Tillmann
- Division of Gastroenterology, Department of Medicine, East Carolina University, Greenville, NC, USA.,Section of Gastroenterology, Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA
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20
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ELITA consensus statements on the use of DAAs in liver transplant candidates and recipients. J Hepatol 2017; 67:585-602. [PMID: 28323126 DOI: 10.1016/j.jhep.2017.03.006] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 03/01/2017] [Accepted: 03/09/2017] [Indexed: 02/07/2023]
Abstract
The advent of safe and highly effective direct-acting antiviral agents (DAAs) has had huge implications for the hepatitis C virus (HCV) transplant field, and changed our management of both patients on the waiting list and those with HCV graft re-infection after liver transplantation (LT). When treating HCV infection before LT, HCV re-infection of the graft can be prevented in nearly all patients. In addition, some candidates show a remarkable clinical improvement and may be delisted. Alternatively, HCV infection can be treated post-LT either soon after the transplant, taking advantage of the removal of the infected native liver, or at the time of disease recurrence, as was carried out in the past. In either case, some DAAs have a limited use because of their drug to drug interactions with various immunosuppressants as well as the many other drugs liver transplant recipients are often prescribed. In addition, some DAAs should be avoided in case of severe renal failure, which is not an unusual complication after LT. The present document provides a series of consensus statements on the LT issues that have not been extensively addressed previously. These statements have been developed to support physicians and other stakeholders in charge of LT candidates and recipients when deciding to treat HCV, especially in difficult situations.
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21
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Joglekar K, Eason JD, Molnar MZ. Do we really need more evidence to use hepatitis C positive donor kidney more liberally? Clin Kidney J 2017; 10:560-563. [PMID: 28835817 PMCID: PMC5561329 DOI: 10.1093/ckj/sfx067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 05/31/2017] [Indexed: 01/15/2023] Open
Abstract
The number of patients listed active for kidney transplantation has continued to rise over the last 10 years, leading to significantly increased wait-list time for patients awaiting kidney transplantation in the USA. This increased demand has led to a supply–demand mismatch and should prompt clinicians to seek timely solutions to improve access to available organs. Hepatitis C virus positive [HCV(+)] kidneys continue to be discarded without clear evidence that they lead to poor outcomes in the current era of highly efficacious HCV treatment with direct-acting antiviral agents (DAAs). Increased utilization of HCV(+) donor kidneys will decrease wait-list time and improve availability of donor organs. Emerging data suggests that HCV can be successfully treated with DAAs after kidney transplantation with 100% sustained virologic response rates and no significant changes from baseline kidney function. Utilization of HCV(+) donor kidneys should be considered more liberally in the era of highly effective HCV treatment. Further studies are warranted to assess the long-term effect of HCV(+) donor kidneys in transplant recipients in the new era of DAAs.
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Affiliation(s)
- Kiran Joglekar
- Department of Internal Medicine, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - James D Eason
- Division of Transplant Surgery, Methodist University Hospital Transplant Institute, Memphis, TN, USA.,Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Miklos Z Molnar
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.,Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
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22
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Cohen JB, Eddinger KC, Shelton B, Locke JE, Forde KA, Sawinski D. Effect of kidney donor hepatitis C virus serostatus on renal transplant recipient and allograft outcomes. Clin Kidney J 2017; 10:564-572. [PMID: 28852496 PMCID: PMC5569958 DOI: 10.1093/ckj/sfx048] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
Background Hepatitis C virus (HCV) infection is common in dialysis patients and renal transplant recipients and has been associated with diminished patient and allograft survival. HCV-positive (HCV+) kidneys have been used in HCV-positive (HCV+) recipients as a means of facilitating transplantation and expanding the organ donor pool; however, the effect of donor HCV serostatus in the modern era is unknown. Methods Using national transplant registry data, we created a propensity score–matched cohort of HCV+ recipients who received HCV-positive donor kidneys compared to those transplanted with HCV-negative kidneys. Results Transplantation with an HCV+ kidney was associated with an increased risk of death {hazard ratio [HR] 1.43 [95% confidence interval (CI) 1.18–1.76]; P < 0.001} and allograft loss [HR 1.39 (95% CI 1.16–1.67); P < 0.001] compared with their propensity score–matched counterparts. However, HCV+ kidneys were not associated with an increased risk of acute rejection [odds ratio 1.16 (95% CI 0.84–1.61); P = 0.35]. Conclusions While use of HCV+ donor kidneys can shorten the wait for renal transplantation and maximize organ utility for all candidates on the waiting list, potential recipients should be counseled about the increased risks associated with HCV+ kidney.
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Affiliation(s)
- Jordana B Cohen
- Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA
| | - Kevin C Eddinger
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Brittany Shelton
- Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jayme E Locke
- Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Kimberly A Forde
- Department of Medicine, Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA.,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Deirdre Sawinski
- Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA
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23
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Shah AP, Cameron A, Singh P, Frank AM, Fenkel JM. Successful treatment of donor-derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens. Transpl Infect Dis 2017; 19. [PMID: 28060446 DOI: 10.1111/tid.12660] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 07/21/2016] [Accepted: 11/17/2016] [Indexed: 12/12/2022]
Abstract
We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to three HCV-negative recipients-two renal transplants and one liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner. Recipient 1 was a 45-year-old man with a history of end-stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62-year-old woman with a history of end-stage renal disease caused by hypertension and insulin-dependent diabetes. Recipient 3 was a 42-year-old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post-transplant follow-up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor-derived HCV in transplant recipients.
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Affiliation(s)
- Ashesh P Shah
- Transplant Division, Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Andrew Cameron
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Pooja Singh
- Division of Nephrology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Adam M Frank
- Transplant Division, Department of Surgery, Thomas Jefferson University, Philadelphia, PA, USA
| | - Jonathan M Fenkel
- Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
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24
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Gallegos-Orozco JF, Kim R, Thiesset HF, Hatch J, Lynch K, Chaly T, Shihab F, Ahmed F, Hall I, Campsen J. Early Results of Pilot Study Using Hepatitis C Virus (HCV) Positive Kidneys to Transplant HCV Infected Patients with End-Stage Renal Disease Allowing for Successful Interferon-Free Direct Acting Antiviral Therapy after Transplantation. Cureus 2016; 8:e890. [PMID: 28018760 PMCID: PMC5179247 DOI: 10.7759/cureus.890] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 11/22/2016] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection in kidney transplant (KTX) patients reduces long-term patient and graft survival. Direct-acting antivirals (DAA) are > 90% effective in achieving sustained viral response (SVR); however, DAAs are not routinely available to patients with end-stage renal disease (ESRD). The University of Utah Transplant Program developed a protocol to allow HCV-positive potential KTX recipients to accept HCV-positive donors' kidneys. Three months after successful KTX, they were eligible for DAA therapy. METHODS HCV-positive patients approved for KTX by the University of Utah Transplant Selection Committee were eligible to be enrolled in this study. Patients consented for the use of HCV-positive donor organs. Three to six months after successful KTX, these patients were treated for HCV with interferon-free direct-acting antiviral regimens according to viral genotype and prior treatment experience. RESULTS Between 2014-2015, 12 HCV-positive patients were listed for KTX. Eight patients were kidney only eligible, seven patients received HCV-positive deceased donor kidneys, and one received an HCV-negative organ. Currently, six patients have completed treatment, all have achieved sustained viral response (SVR), and one patient is currently awaiting treatment. All seven patients have functioning kidney grafts. Wait time for KTX was reduced amongst all blood groups from an average of 1,350 days to only 65 days. CONCLUSIONS HCV-positive patients with ESRD can successfully receive an HCV-positive donor's kidney. Once transplanted, these patients can receive DAA therapy and achieve SVR. Use of HCV-positive organs reduced time on the waitlist by greater than three years and expanded the donor organ pool.
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Affiliation(s)
| | - Robin Kim
- General Surgery, University of Utah School of Medicine
| | | | - Jenny Hatch
- Internal Medicine, Gastroenterology, University of Utah School of Medicine
| | - Keisa Lynch
- Internal Medicine, Gastroenterology, University of Utah School of Medicine
| | - Thomas Chaly
- Division of Transplantation and Advanced Hepatobiliary Surgery, University of Utah School of Medicine
| | - Fuad Shihab
- Internal Medicine, Nephrology, University of Utah School of Medicine
| | - Faris Ahmed
- Internal Medicine, Nephrology, University of Utah School of Medicine
| | - Isaac Hall
- Internal Medicine, Nephrology, University of Utah School of Medicine
| | - Jeffrey Campsen
- Division of Transplantation and Advanced Hepatobiliary Surgery, University of Utah School of Medicine
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25
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Nowak KM, Witzke O, Sotiropoulos GC, Benkö T, Fiedler M, Timm J, Kribben A, Wilde B, Saner F, Paul A, Treckmann J. Transplantation of Renal Allografts From Organ Donors Reactive for HCV Antibodies to HCV-Negative Recipients: Safety and Clinical Outcome. Kidney Int Rep 2016; 2:53-59. [PMID: 29142940 PMCID: PMC5678640 DOI: 10.1016/j.ekir.2016.09.058] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 09/01/2016] [Accepted: 09/23/2016] [Indexed: 01/17/2023] Open
Abstract
Introduction Because of the shortage of available organs for renal transplantation, strategies enabling the safe use of organs from donors with potential chronic infections such as hepatitis C are necessary. The aim of this study was to analyze the outcome of renal transplant donation from hepatitis C virus (HCV)-positive donors. Methods Between September 2002 and May 2007, 51 kidneys (34 donors) reactive for HCV antibodies were further evaluated. Six kidneys (5 donors) were transplanted to 6 recipients with known chronic HCV infection. The remaining 29 donors underwent extended virological testing. Nine donors were HCV RNA positive and thus not suitable for HCV-negative patients. Twenty donors (21 kidneys) did not have detectable HCV RNA copies and were transplanted into 21 HCV-negative recipients. Clinical outcomes focusing on safety, allograft function, and de novo HCV infection in the recipient were collected. Results There were no de novo HCV infections detected in recipients who were HCV negative before transplantation. The extended virological donor screening did not have an impact on median cold ischemia time. Five-year graft survival was 75%. Discussion Organs from anti-HCV-reactive, nonviremic donors can be transplanted safely to HCV-negative recipients.
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Affiliation(s)
- Knut Michael Nowak
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Oliver Witzke
- Department of Nephrology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.,Department of Infectious Diseases, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Georgios C Sotiropoulos
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Tamas Benkö
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Melanie Fiedler
- Institute of Virology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Jörg Timm
- Institute of Virology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Andreas Kribben
- Department of Nephrology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Benjamin Wilde
- Department of Nephrology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Fuat Saner
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Andreas Paul
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
| | - Jürgen Treckmann
- Department of General, Visceral and Transplantation Surgery, University of Duisburg-Essen, University Hospital Essen, Essen, Germany
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Assessment of 4 Cases of Kidney Transplantation from Hepatitis C Virus Antibody-Positive and RNA-Negative Donors to Antibody-Negative Recipients. Transplant Direct 2016; 2:e102. [PMID: 27795994 PMCID: PMC5068204 DOI: 10.1097/txd.0000000000000614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2016] [Accepted: 07/17/2016] [Indexed: 12/18/2022] Open
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Belga S, Doucette KE. Hepatitis C in non-hepatic solid organ transplant candidates and recipients: A new horizon. World J Gastroenterol 2016; 22:1650-63. [PMID: 26819530 PMCID: PMC4721996 DOI: 10.3748/wjg.v22.i4.1650] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 09/20/2015] [Accepted: 11/24/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is estimated to affect 130-150 million people globally which corresponds to 2%-3% of the total world population. It remains the leading indication for liver transplant worldwide and has been demonstrated to negatively impact both patient and graft survival following non-hepatic organ transplantation. In the era of interferon-based therapy, although treatment and cure of HCV prior to non-hepatic transplant improved survival, tolerability and low cure rates substantially limited therapy. Interferon (IFN)-based therapy following non-hepatic solid organ transplant, due to the risk of allograft rejection, is generally contraindicated. Rapid advances in IFN-free therapy with direct acting antivirals (DAAs) in the last few years have completely changed the paradigm of hepatitis C therapy. Compared to IFN-based regimens, DAAs have less frequent and less severe adverse effects, shorter durations of therapy, and higher cure rates that are minimally impacted by historically negative predictors of response such as cirrhosis, ethnicity, and post-transplant state. Recent studies have shown that liver transplant (LT) recipients can be safely and effectively treated with DAA combination therapies; although data are limited, many of the principles of therapy in LT may be extrapolated to non-hepatic solid organ transplant recipients. Here we review the data on DAA combination therapies in transplantation, discuss the advantages and disadvantages of pre- vs post-transplant HCV therapy and future directions.
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Morales JM, Martinez-Flores JA, Serrano M, Serrano A, Dominguez-Gil B. What are the management issues for hepatitis C in dialysis patients?: renal transplantation from hepatitis C-positive donors. Semin Dial 2015; 27:459-62. [PMID: 25204880 DOI: 10.1111/sdi.12293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Jose M Morales
- Instituto de Investigacion Hospital 12 de Octubre, Madrid, Spain
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Shorter Waitlist Times and Improved Graft Survivals Are Observed in Patients Who Accept Hepatitis C Virus+ Renal Allografts. Transplantation 2015; 99:1192-6. [DOI: 10.1097/tp.0000000000000479] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Jr CSK, Koval CE, Duin DV, Morais AGD, Gonzalez BE, Avery RK, Mawhorter SD, Brizendine KD, Cober ED, Miranda C, Shrestha RK, Teixeira L, Mossad SB. Selecting suitable solid organ transplant donors: Reducing the risk of donor-transmitted infections. World J Transplant 2014; 4:43-56. [PMID: 25032095 PMCID: PMC4094952 DOI: 10.5500/wjt.v4.i2.43] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Revised: 03/21/2014] [Accepted: 05/14/2014] [Indexed: 02/05/2023] Open
Abstract
Selection of the appropriate donor is essential to a successful allograft recipient outcome for solid organ transplantation. Multiple infectious diseases have been transmitted from the donor to the recipient via transplantation. Donor-transmitted infections cause increased morbidity and mortality to the recipient. In recent years, a series of high-profile transmissions of infections have occurred in organ recipients prompting increased attention on the process of improving the selection of an appropriate donor that balances the shortage of needed allografts with an approach that mitigates the risk of donor-transmitted infection to the recipient. Important advances focused on improving donor screening diagnostics, using previously excluded high-risk donors, and individualizing the selection of allografts to recipients based on their prior infection history are serving to increase the donor pool and improve outcomes after transplant. This article serves to review the relevant literature surrounding this topic and to provide a suggested approach to the selection of an appropriate solid organ transplant donor.
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Seem DL, Lee I, Umscheid CA, Kuehnert MJ. PHS guideline for reducing human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission through organ transplantation. Public Health Rep 2013; 128:247-343. [PMID: 23814319 DOI: 10.1177/003335491312800403] [Citation(s) in RCA: 178] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Debbie L Seem
- Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Healthcare Quality Promotion, Office of Blood, Organ, and other Tissue Safety, Atlanta, GA 30329, USA.
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Levitsky J, Doucette K. Viral hepatitis in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:147-68. [PMID: 23465008 DOI: 10.1111/ajt.12108] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- J Levitsky
- Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Abstract
PURPOSE OF REVIEW Transplantation of kidneys from donors with a positive serology for hepatitis C virus (HCVD positive) remains controversial. RECENT FINDINGS Registry studies reported that the use of HCVD positive kidneys into HCV positive recipients is associated with shorter time awaiting transplantation but with a small increase in hazard for death and graft loss compared with HCVD negative. Notably, patients who received kidneys from HCVD positive have better survival than those who remain in the waitlist. A collaborative study using HCVD positive kidneys into HCVRNA positive recipients showed that HCV serology was not an independent risk factor for liver disease, graft survival, and patient survival in the long term. The safety of this approach can be improved by matching donors and recipients according to HCV genotypes. Because the incidence and prevalence of HCV infection in dialysis patients are decreasing, kidneys from HCVD positive are becoming surplus organs due to the lack of appropriate recipients in the waitlist. To improve the underutilization of these kidneys, organizational measures, including the offer of these kidneys for preemptive transplantation, are suggested. SUMMARY The use of kidneys from HCVD positive into HCVR positive seems to be a safe approach in the long term, showing a better patient survival than that of HCV positive patients on the waitlist.
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Singh N, Neidlinger N, Djamali A, Leverson G, Voss B, Sollinger HW, Pirsch JD. The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience. Clin Transplant 2012; 26:684-93. [PMID: 22283142 DOI: 10.1111/j.1399-0012.2011.01583.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The survival benefit of transplanting hepatitis C (HCV)-positive donor kidneys into HCV-positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV-status of the donor (D) kidney on the long-term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased-donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D-/R- (n = 1897), D-/R+ (n = 59), D+/R- (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox-proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted-hazard ratio [HR] 2.1, 95% CI [1.4-2.9]) with respect to the reference D-/R- group, whereas mortality was not increased in D-/R+ group. The rate of graft loss was increased in both D+/R+ and D-/R+ but was comparable with each other (adjusted-HR 1.8, 95% CI [1.4-2.5]) vs. adjusted-HR 2.0, 95% CI [1.4-2.8], respectively). D-/R+ cohort experienced significantly higher rate of rejection (adjusted-HR 1.7, 95% CI [1.2-2.5]) and chronic allograft nephropathy (adjusted-HR 2.1, 95% CI [1.2-3.7]). Neither donor nor recipient HCV-status impacted the risk of recurrent or de novo GN. Transplanting HCV-positive kidneys as opposed to HCV-negative kidneys into HCV-positive recipients provided similar graft survival but compromised patient survival in the long term.
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Affiliation(s)
- Neeraj Singh
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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Carbone M, Cockwell P, Neuberger J. Hepatitis C and kidney transplantation. Int J Nephrol 2011; 2011:593291. [PMID: 21755059 PMCID: PMC3132687 DOI: 10.4061/2011/593291] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2011] [Revised: 03/05/2011] [Accepted: 04/13/2011] [Indexed: 12/17/2022] Open
Abstract
Hepatitis C virus (HCV) infection is relatively common among patients with end-stage kidney disease (ESKD) on dialysis and kidney transplant recipients. HCV infection in hemodialysis patients is associated with an increased mortality due to liver cirrhosis and hepatocellular carcinoma. The severity of hepatitis C-related liver disease in kidney transplant candidates may predict patient and graft survival after transplant. Liver biopsy remains the gold standard in the assessment of liver fibrosis in this setting. Kidney transplantation, not haemodialysis, seems to be the best treatment for HCV+ve patients with ESKD. Transplantation of kidneys from HCV+ve donors restricted to HCV+ve recipients is safe and associated with a reduction in the waiting time. Simultaneous kidney/liver transplantation (SKL) should be considered for kidney transplant candidates with HCV-related decompensated cirrhosis. Treatment of HCV is more complex in hemodialysis patients, whereas treatment of HCV recurrence in SLK recipients appears effective and safe.
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Affiliation(s)
- Marco Carbone
- Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
| | - Paul Cockwell
- Department of Nephrology, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
| | - James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH, UK
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High infectious risk donors: what are the risks and when are they too high? Curr Opin Organ Transplant 2011; 16:256-61. [DOI: 10.1097/mot.0b013e3283449dd3] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Maluf DG, Archer KJ, Mas VR. Kidney grafts from HCV-positive donors: advantages and disadvantages. Transplant Proc 2011; 42:2436-46. [PMID: 20832522 DOI: 10.1016/j.transproceed.2010.04.056] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Accepted: 04/01/2010] [Indexed: 02/08/2023]
Abstract
The Organ Procurement and Transplantation Network database (2001-2006) was reviewed for kidney transplant (KT) recipients, to evaluate the effects of use of grafts from donors positive for hepatitis C virus (HCV) on recipient outcome. Data for 76,787 de novo adult KT recipients were included in the analysis. Serologic tests revealed HCV positivity in 6.25% of cadaver kidneys and 2.97% of living-donor kidneys. Median follow-up in patients still alive was 36 months. At multivariable Cox regression analysis in recipients of cadaver kidney, HCV serostatus was significantly associated with overall and graft survival (both P < .001), with a hazard ratio for HCV-positive patients of 1.43 for overall survival and 1.48 for graft survival. Similar results were obtained for living-donor kidney recipients. Recipients of HCV-positive organs tended to be male and African American and to have a shorter waiting time. Infection was the most commonly reported cause of death in recipients of organs from HCV-positive donors. In patients willing to accept HCV-positive grafts (929 [25.6%]), waiting time was significantly shortened (P < .001). However, this benefit was offset by decreased patient survival (P < .001) and graft survival (P = .007).
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Affiliation(s)
- D G Maluf
- Virginia Commonwealth University Medical Center, Richmond, 23298-0057, USA.
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Abstract
Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection in potential kidney transplant candidates-once considered absolute contraindications to kidney transplantation-no longer creates overt barriers to transplantation. Advances in the medical management of HBV and HCV infection have created opportunities for a substantial number of patients to be effectively treated with antiviral therapy before transplantation. For HBV infection, a number of new drugs enable clearance of the virus with minimal adverse effects and drug resistance. Pretransplantation antiviral therapy is advisable for patients with HCV infection, but adverse effects are common and viral eradication remains challenging. Regardless of viral clearance, pretransplant patients without bridging fibrosis (as confirmed by liver biopsy) or clinical stigmata of cirrhosis should be considered for kidney transplantation as survival is superior when compared to treatment with dialysis, and progression of liver disease is unlikely. For patients with advanced liver disease, simultaneous liver-kidney transplantation is an important consideration. These treatment advances further increase the burden of organ donor shortage; however, organs from deceased donors with chronic HBV or HCV infection could be efficiently allocated to certain individuals with a viral infection of the same type to increase the pool of available transplant organs.
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Affiliation(s)
- Janna Huskey
- Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA
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40
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Morales JM, Campistol JM, Domínguez-Gil B, Andrés A, Esforzado N, Oppenheimer F, Castellano G, Fuertes A, Bruguera M, Praga M. Long-term experience with kidney transplantation from hepatitis C-positive donors into hepatitis C-positive recipients. Am J Transplant 2010; 10:2453-62. [PMID: 20977636 DOI: 10.1111/j.1600-6143.2010.03280.x] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Kidney transplantation from hepatitis C virus (HCV) antibody positive donors (HCVD+) into HCV antibody positive recipients (HCVR+) is controversial. We implemented this policy in our units in 1990. Herein, we report the long-term safety of this strategy. From March 1990 to March 2007, 162 HCVR+ received a kidney from HCVD+ (group 1) and 306 from HCVD- (group 2) in our units. Mean follow-up was 74.5 months. Five-and 10-year patient survival was 84.8% and 72.7% in group 1 vs. 86.6% and 76.5% in group 2 (p = 0.250). Three deaths in group 1 and two in group 2 were liver-disease related. Five- and 10-year graft survival was 58.9% and 34.4% versus 65.5% and 47.6% respectively (p = 0.006) while death-censored graft survival was 69% and 47% versus 72.7% and 58.5% (p = 0.055). Decompensated chronic liver disease was similar: 10.3% versus 6.2%. Cox-regression analysis could not identify the donor's HCV serology as a significant risk factor for death, graft failure and severe liver disease in HCVR+. In conclusion, long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease. HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+. These data strongly suggest that the use of kidneys from HCVD+ in HCVR+ is a safe long-term strategy that helps to prevent kidney loss.
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Affiliation(s)
- J M Morales
- Nephrology Department, Hospital 12 de Octubre, Madrid, Spain.
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41
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The effect of recipient hepatitis C virus infection on outcomes following heart transplantation. Transplant Proc 2010; 42:1784-7. [PMID: 20620523 DOI: 10.1016/j.transproceed.2009.12.061] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Accepted: 12/02/2009] [Indexed: 12/17/2022]
Abstract
BACKGROUND Insufficient data exist on the clinical course of hepatitis C virus (HCV) infection in heart transplant (HT) recipients. Our study reports the outcomes of heart transplantation in pretransplantation HCV-positive (HCV+) recipients. METHODS A retrospective analysis of the heart transplantation database at our institution was performed to identify HT recipients who were HCV+ prior to transplantation. Chart reviews yielded demographic features, liver function tests, graft function, incidence of posttransplantation acute hepatitis and transplant coronary artery disease, and patient survival data. RESULTS Between 1995 and 2006, 10 HCV+ patients underwent cardiac transplantation. The recipient mean age was 47 years (range, 23-69). Seven recipients were males and 3 were females. At listing 9 patients had no cirrhosis. One patient with Child-B cirrhosis was listed for combined heart-liver transplantation. Two of 10 donors were known to be HCV carriers. Posttransplantation in-hospital survival rate was 100%. At a mean follow-up of 58 months (range, 1.6-145), 3 deaths occurred, yielding an overall survival rate of 70%. Only 1 death (10%) was linked to accelerated acute hepatitis. Transplant coronary artery disease was detected in 2 patients (20%). Echocardiograms of survivors at last follow-up revealed normal ejection fractions. In addition, there were no cases of hepatocellular carcinoma; all survivors were without evidence of hepatic dysfunction. CONCLUSIONS Transplanting recipients known to have HCV did not seem to affect overall posttransplantation survival or to increase the risk of liver dysfunction or graft-related complications.
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Kucirka LM, Singer AL, Ros RL, Montgomery RA, Dagher NN, Segev DL. Underutilization of hepatitis C-positive kidneys for hepatitis C-positive recipients. Am J Transplant 2010; 10:1238-46. [PMID: 20353475 DOI: 10.1111/j.1600-6143.2010.03091.x] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Hepatitis C-positive (HCV(+)) candidates likely derive survival benefit from transplantation with HCV(+) kidneys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data has led to wide practice variation. Our goal was to characterize national utilization of HCV(+) kidneys for HCV(+) recipients, and to quantify the risks/benefits of this practice. Of 93,825 deceased donors between 1995 and 2009, HCV(+) kidneys were 2.60-times more likely to be discarded (p < 0.001). However, of 6830 HCV(+) recipients, only 29% received HCV(+) kidneys. Patients over 60 relative rate (RR 0.86), women (RR 0.73) and highly sensitized patients (RR 0.42) were less likely to receive HCV(+) kidneys, while African Americans (RR 1.56), diabetics (RR 1.29) and those at centers with long waiting times (RR 1.19) were more likely to receive them. HCV(+) recipients of HCV(+) kidneys waited 310 days less than the average waiting time at their center, and 395 days less than their counterparts at the same center who waited for HCV(-) kidneys, likely offsetting the slightly higher patient (HR 1.29) and graft loss (HR 1.18) associated with HCV(+) kidneys. A better understanding of the risks and benefits of transplanting HCV(+) recipients with HCV(+) kidneys will hopefully improve utilization of these kidneys in an evidence-based manner.
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Affiliation(s)
- L M Kucirka
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Kucirka LM, Dagher NN, Montgomery RA, Segev DL, Singer AL. High infectious risk organ donors in kidney transplantation: Risks, benefits, and current practices. ACTA ACUST UNITED AC 2010. [DOI: 10.1002/dat.20442] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Abstract
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most common and serious causes of liver damage in patients with chronic kidney disease (CKD). The natural histories of HBV and HCV infections in patients with CKD are not fully understood; however, recent evidence has emphasized the adverse effect of HBV and/or HCV infection on survival in this population. Chronic liver disease is the fourth most important cause of death after renal transplantation. The negative effect of HCV infection on survival among renal transplant recipients has been linked to liver dysfunction and extrahepatic complications, such as chronic glomerulonephritis, post-transplantation diabetes mellitus, chronic allograft nephropathy, and sepsis. The transmission of HCV by solid organ transplantation has been unequivocally demonstrated. Renal transplant recipients who receive kidneys from HCV-positive donors are at increased risk of death. Although several studies have shown that in patients with HCV infection and chronic renal failure renal transplantation is associated with better survival than is dialysis, recent clinical guidelines recommend that kidneys from HCV-infected donors should not be used in HCV-seropositive recipients without detectable HCV viremia. Monotherapy with conventional interferon has been suggested to be a useful treatment for hepatitis C infection in patients on dialysis. Although no evidence suggests that patients with CKD are more prone to suffer from hepatic toxic effects than individuals with normal kidney function, patients with CKD usually receive multiple medications; and drug interactions may, therefore, have a role in the pathogenesis of drug-induced liver disease in this population.
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Affiliation(s)
- J Levitsky
- Division of Hepatology and Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Fabrizi F, Messa P, Martin P. Current status of renal transplantation from HCV-positive donors. Int J Artif Organs 2009; 32:251-61. [PMID: 19569034 DOI: 10.1177/039139880903200502] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Hepatitis C virus (HCV) infection remains frequent among renal transplant (RT) recipients and has a detrimental effect on patient and graft survival. accelerated progression of liver disease due to HCV has been implicated in increased mortality after kidney transplantation but additional outcomes have been related to HCV after RT. all HCV-infected kidney transplant candidates should be considered for liver biopsy before RT. HCV infection should not be considered an absolute contraindication to renal transplantation, although the course of HCV-related liver disease is often progressive. Numerous organ procurement organizations have introduced the policy of accepting kidneys from HCV-positive donors for HCV-positive recipients, but this is still controversial. Single-center experiences have not reported adverse effects on the short-term patient and graft survival, however information from large databases has suggested that RT recipients of HCV-positive donors are independently at risk of mortality even in the modern era of immunosuppression. Renal transplantation should be considered using HCV-seropositive grafts for qualified patients with chronic kidney disease (CKD) stage 5 and HCV infection since good information indicates that the transplantation of kidneys from HCV-infected donors results in improved survival compared to wait-listed and dialysis-dependent candidates. a potential risk related to the use of donor HCV-positive kidneys cannot be excluded, and kidneys from HCV-infected donors should be restricted to recipients with evidence of active viremia at the time of kidney transplantation.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology and Dialysis, Maggiore Hospital, IRCCS Foundation, Milan, Italy.
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Snyder JJ, Israni AK, Peng Y, Zhang L, Simon TA, Kasiske BL. Rates of first infection following kidney transplant in the United States. Kidney Int 2008; 75:317-26. [PMID: 19020531 DOI: 10.1038/ki.2008.580] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
We studied the incidence, trends and clinical correlates of infections following kidney transplantation in the United States Renal Data System over the years 1995-2003 in 46,471 adults with Medicare primary coverage at the time of their first kidney transplant. The incidence of most infections has declined only slightly since 1995 but infection with cytomegalovirus significantly declined while that with hepatitis C significantly increased. Relative frequencies of different types of infections (bacterial, viral, fungal and parasitic) were relatively constant, both during early and late periods following transplant. Using the Cox proportional hazards analysis we found that the clinical correlates for post-transplant bacterial and viral infections included older age, female gender, diabetes as the cause of end-stage renal disease, deceased (vs. living) donor source, time on dialysis before transplant, hepatitis B and C viral pre-transplant serologic status and pre-transplant donor-recipient cytomegalovirus serology. Our study shows that despite identifiable risk factors, the incidence of most post-transplant infections has changed little since 1995.
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Affiliation(s)
- Jon J Snyder
- Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota 55404, USA.
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48
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Abstract
Hepatitis C virus (HCV) infection remains frequent in patients on renal replacement therapy and has an adverse impact on survival in infected patients on chronic hemodialysis as well as renal transplant (RT) recipients. Nosocomial spread of HCV within dialysis units continues to occur. HCV is also implicated in the pathogenesis of renal dysfunction often mediated by cryoglobulins leading to chronic kidney disease as well as impairing renal allograft function. The role of antiviral therapy for hepatitis C in patients with renal failure remains unclear. Monotherapy with conventional interferon (IFN) for chronic hepatitis C is probably more effective in dialysis than in non-uraemic patients but tolerance is lower. Limited data only are available about monotherapy with pegylated interferon and combination therapy (pegylated IFN plus ribavirin) for chronic HCV in the dialysis population. Clinical experience with antiviral therapy for acute HCV in dialysis population is encouraging. Interferon remains contraindicated post-RT because of concerns about precipitating graft dysfunction. Sustained viral responses obtained by antiviral therapy in renal transplant candidates are durable after renal transplantation and may reduce HCV-related complications after RT (post-transplant diabetes mellitus, HCV-related glomerulonephritis, and chronic allograft nephropathy).
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Affiliation(s)
- Paul Martin
- Center for Liver Diseases, Miller School of Medicine, Department of Medicine, University of Miami, Miami, FL 33136, USA.
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49
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Abstract
Chronic hepatitis C virus (HCV) infection remains an important cause of liver disease in patients with end-stage renal disease (ESRD) and conversely, renal failure has a significant impact on morbidity and mortality throughout the natural history of chronic HCV and its treatment. With improved awareness within dialysis units of the potential for spread and the institution of preventative measures, the prevalence of HCV infection in the hemodialysis-dependent population has continued to decline since 1995. Use of HCV (+) donor kidneys is associated with an increase in the prevalence of liver disease, but when compared with continued hemodialysis, transplantation using these kidneys is associated with improved survival. Overall, survival in patients with chronic HCV infection appears to be better after renal transplantation when compared with maintenance hemodialysis, and transplant should be considered for these patients. Data support the use of interferon and the improved efficacy of pegylated interferon formulations for treatment of chronic HCV infection in ESRD patients, although tolerability continues to be troublesome. The newest and most promising data regarding the treatment of HCV in ESRD involve the combination of reduced dose ribavirin with interferon or pegylated interferon suggesting similar enhancements in sustained virologic response (SVR) as seen in non-ESRD patients, but caution is advised, as all studies to date used ribavirin plasma concentration monitoring in patient with ESRD. Finally, with regard to postrenal transplant treatment of HCV infection, there is no evidence to support treatment with interferon-based therapy and pretransplant treatment remains the best option whenever possible.
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Affiliation(s)
- Emuejevoke J Okoh
- Division of Gastroenterology and Hepatology, Brooke Army Medical Center, Fort Sam Houston, Texas 78234, USA
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