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Kashani M, Karimi M, Sharifi Rayeni A, Azizi Nadian MA, Mortezazadeh M, Parsaei A, Abolghasemi N, Shirsalimi N, Mofidi A, Seyyed Mahmoudi ST. Efficacy of Direct Acting Antivirals (DAA) therapy in patients with recurrent hepatitis C after liver and kidney transplantation: a cross-sectional study. Front Med (Lausanne) 2024; 11:1460372. [PMID: 39444819 PMCID: PMC11496299 DOI: 10.3389/fmed.2024.1460372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 09/05/2024] [Indexed: 10/25/2024] Open
Abstract
Background and objectives Direct-acting antiviral (DAA) agents are now widely used to treat patients with hepatitis C infection (HCV) and effectively increase their sustained virologic response (SVR). However, the literature seems to lack or deficient evidence of DAA efficacy in more complicated patients, especially those with HCV reinfection after liver transplantation (LT) or liver-kidney (hepatorenal) transplantation (LKT). This study aimed to retrospectively evaluate the effectiveness of two different DAA regimens in LT and LKT patients with HCV reinfection. Methods This cross-sectional study was conducted at three hospitals in Tehran, Iran, from 2014 to 2020, enrolling 53 patients with recurrent HCV infection after LT (n = 35) or LKT (n = 18). Patients were treated for 12 weeks with one of two DAA regimens: 37 patients (70%) received Daclatasvir and Sofosbuvir (SOF + DCV), while 16 patients (30%) received Sofosbuvir and Ledipasvir (SOF + LDV). Ribavirin (RBV) was added as an adjunct antiviral in 28 patients (52.8%). To assess the SVR, all patients were followed for 12 weeks after treatment. Results Both DAA regimens were well-tolerated and effective, with 94.6% (35 of 37) achieving SVR-12 in the SOF + DCV group and 93.8% (15 of 16) in the SOF + LDV group. Additionally, SVR-12 rates were promising across treatment durations, with 93.9% (31 of 33) in the 12-week group and 95% (19 of 20) in the 24-week group achieving undetectable HCV RNA. No significant difference in SVR was observed between the two regimens (p = 0.439). Conclusion The DAA-based therapeutic regimen was well tolerated and showed significant effectiveness in achieving the virologic response in patients with HCV reinfection after LT or LKT.
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Affiliation(s)
- Mehdi Kashani
- Department of Gastroenterology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Karimi
- Bogomolets National Medical University (NMU), Kyiv, Ukraine
| | | | | | - Masoud Mortezazadeh
- Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Nooshin Abolghasemi
- Department of Pharmacology, Islamic Azad University - Pharmaceutical Sciences Branch, Tehran, Iran
| | - Niyousha Shirsalimi
- Faculty of Medicine, Hamadan University of Medical Science (UMSHA), Hamadan, Iran
| | - Abbas Mofidi
- Faculty of Medicine, Hamadan University of Medical Science (UMSHA), Hamadan, Iran
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2
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Sharma P, Sawtell R, Wang Q, Sise ME. Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:343-355. [PMID: 37657881 PMCID: PMC10479952 DOI: 10.1053/j.akdh.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 09/03/2023]
Abstract
Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.
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Affiliation(s)
- Purva Sharma
- Department of Medicine, Division of Nephrology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Glomerular Disease Center at Northwell Health, Hempstead, NY
| | - Rani Sawtell
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Qiyu Wang
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
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3
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Strohbehn IA, Seethapathy R, Lee M, Sise ME. Curative Therapies for Hepatitis C Virus Infection in Patients with Kidney Disease. KIDNEY360 2021; 2:1316-1325. [PMID: 35369667 PMCID: PMC8676392 DOI: 10.34067/kid.0001812021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 05/21/2021] [Indexed: 02/04/2023]
Abstract
Through the discovery of direct-acting antiviral therapies over the last decade, hepatitis C virus (HCV) has been transformed from a highly morbid and potentially fatal chronic viral infection to a curable illness. HCV is common in patients with kidney disease, is a risk factor for progression of CKD, is associated with higher morbidity and mortality in patients receiving dialysis, and leads to worse allograft and patient outcomes in recipients of kidney transplants. Clinical trial and real-world data of direct-acting antivirals in patients with kidney disease demonstrate extremely high cure rates and favorable adverse event profiles. This review covers the transformative effects of curative HCV therapies on patients with kidney disease, including patients with CKD, ESKD, and those who have received a kidney transplant.
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Affiliation(s)
- Ian A Strohbehn
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
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4
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Boyarsky BJ, Strauss AT, Segev DL. Transplanting Organs from Donors with HIV or Hepatitis C: The Viral Frontier. World J Surg 2021; 45:3503-3510. [PMID: 33471156 DOI: 10.1007/s00268-020-05924-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2020] [Indexed: 12/21/2022]
Abstract
A wide gap between the increasing demand for organs and the limited supply leads to immeasurable loss of life each year. The organ shortage could be attenuated by donors with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). The transplantation of organs from HIV+ deceased donors into HIV+ individuals (HIV D+ /R+) was initiated in South Africa in 2010; however, this practice was forbidden in the USA until the HIV Organ Policy Equity (HOPE) Act in 2013. HIV D+/R+ transplantation is now practiced in the USA as part of ongoing research studies, helping to reduce waiting times for all patients on the waitlist. The introduction of direct acting antivirals for HCV has revolutionized the utilization of donors with HCV for HCV-uninfected (HCV-) recipients. This is particularly relevant as the HCV donor pool has increased substantially in the context of the rise in deaths related to drug overdose from injection drug use. This article serves to review the current literature on using organs from donors with HIV or HCV.
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Affiliation(s)
- Brian J Boyarsky
- Department of Surgery, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University School of Medicine, 2000 E Monument St, Baltimore, MD, 21205, USA
| | - Alexandra T Strauss
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Dorry L Segev
- Department of Surgery, Epidemiology Research Group in Organ Transplantation, Johns Hopkins University School of Medicine, 2000 E Monument St, Baltimore, MD, 21205, USA. .,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
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5
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Kapila N, Menon KVN, Al-Khalloufi K, Vanatta JM, Murgas C, Reino D, Ebaid S, Shaw JJ, Agrawal N, Rhazouani S, Navas V, Sheffield C, Rahman AU, Castillo M, Lindenmeyer CC, Miller C, Quintini C, Zervos XB. Hepatitis C Virus NAT-Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus-Negative Recipients: A Real-World Experience. Hepatology 2020; 72:32-41. [PMID: 31659775 DOI: 10.1002/hep.31011] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 10/22/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIMS Hepatitis C virus (HCV)-viremic organs are underutilized, and there is limited real-world experience on the transplantation of HCV-viremic solid organs into recipients who are HCV negative. APPROACH AND RESULTS Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV-viremic organs. All recipients were HCV nucleic acid test and anti-HCV antibody negative at the time of transplant and received an HCV-viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct-acting antiviral (DAA) therapy (SVR12 ). Seventy-seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty-four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty-one achieved SVR12 , 10 had undetectable viral loads but are not eligible for SVR12 , and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver-kidney transplant. Three patients achieved SVR12 , 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart-kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. CONCLUSIONS Limited data exist on the transplantation of HCV-viremic organs into recipients who are HCV negative. Our study is the largest to describe a real-world experience of the transplantation of HCV-viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV-viremic grafts in the DAA era appears to be efficacious and well tolerated.
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Affiliation(s)
- Nikhil Kapila
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL.,Department of Gastroenterology and Hepatology, Duke University, Durham, NC
| | | | | | - Jason M Vanatta
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Carla Murgas
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Diego Reino
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Samer Ebaid
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Joshua J Shaw
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Neerja Agrawal
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Salwa Rhazouani
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | - Viviana Navas
- Department of Transplant, Cleveland Clinic Florida, Weston, FL
| | | | - Asad Ur Rahman
- Department of Gastroenterology and Hepatology, Cleveland Clinic Florida, Weston, FL
| | | | | | - Charles Miller
- Department of Transplant, Cleveland Clinic, Cleveland, OH
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6
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Lawitz E, Flisiak R, Abunimeh M, Sise ME, Park JY, Kaskas M, Bruchfeld A, Wörns MA, Aglitti A, Zamor PJ, Xue Z, Schnell G, Jalundhwala YJ, Porcalla A, Mensa FJ, Persico M. Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection. Liver Int 2020; 40:1032-1041. [PMID: 31821716 DOI: 10.1111/liv.14320] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/20/2019] [Accepted: 11/27/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS Chronic hepatitis C virus (HCV) infection increases the risk of incident chronic kidney disease (CKD) and progression to end-stage renal disease (ESRD). Previously available direct-acting antiviral regimens are not approved for patients with advanced CKD across all HCV genotypes. METHODS EXPEDITION-5 is a phase 3 study to evaluate efficacy and safety of the fixed-dose combination of glecaprevir and pibrentasvir (G/P) for chronic HCV infection (genotype 1 through 6) in adults without cirrhosis or with compensated cirrhosis and with stage 3b, 4 or 5 CKD. Patients received approved duration of G/P according to HCV genotype, cirrhosis status and prior HCV treatment experience. The primary efficacy endpoint was percentage of patients with sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS Among the 101 patients enrolled in the study, 24% had predialysis CKD and 76% were on dialysis. Eighty-four patients were treated with G/P for 8 weeks, 13 patients for 12 weeks and four patients for 16 weeks. Fifty-five per cent of patients had genotype 1, 27% had genotype 2, 15% had genotype 3 and 4% had genotype 4, and none had genotype 5 or 6 infection. The SVR12 rate was 97% (98/101, 95% confidence interval, 91.6-99.0). No patients experienced virologic failure. Adverse events (AEs) reported in at least 5% of the patients were pruritus, bronchitis, hypertension and generalized pruritus. Serious AEs were reported in 12% of patients; none related to study drug. CONCLUSIONS G/P treatment yielded high SVR12 rates irrespective of the presence of stage 3b, 4 or 5 CKD. No safety signals were detected. CLINICALTRIALS. GOV IDENTIFIER This Phase 3 clinical trial was funded by AbbVie and registered with clinicaltrials.gov as NCT03069365 (EXPEDITION-5).
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Affiliation(s)
- Eric Lawitz
- The Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | | | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA
| | - Jun Y Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | | | - Annette Bruchfeld
- Department of Renal Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Marcus-Alexander Wörns
- Department of Internal Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | | | | | | | | | | | | | - Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
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7
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Sise ME, Strohbehn IA, Bethea E, Gustafson JL, Chung RT. Balancing the risk and rewards of utilizing organs from hepatitis C viremic donors. Curr Opin Organ Transplant 2019; 24:351-357. [PMID: 31090648 PMCID: PMC7093034 DOI: 10.1097/mot.0000000000000651] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW Owing to long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of hepatitis C viremic-deceased donor organs are under investigation in kidney, liver, heart, and lung transplantation. RECENT FINDINGS Direct-acting antiviral medications for hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early posttransplant direct-acting antiviral therapy, 100% of uninfected recipients of hepatitis C viremic organs have been cured of infection after transplantation. SUMMARY In this manuscript, we review the risks and rewards of utilizing hepatitis C viremic organs for transplantation.
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Affiliation(s)
- Meghan E. Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital
| | - Ian A. Strohbehn
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Emily Bethea
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Jenna L. Gustafson
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
| | - Raymond T. Chung
- Department of Medicine, Liver Center, Gastrointestinal Division, Massachusetts General Hospital
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8
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Reddy YNV, Nunes D, Chitalia V, Gordon CE, Francis JM. Hepatitis C virus infection in kidney transplantation-changing paradigms with novel agents. Hemodial Int 2019; 22 Suppl 1:S53-S60. [PMID: 29694721 DOI: 10.1111/hdi.12659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha-based therapies that were difficult to tolerate and were associated with adverse side-effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side-effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon-based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct-acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation.
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Affiliation(s)
- Yuvaram N V Reddy
- Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA
| | - David Nunes
- Division of Gastroenterology, Boston University Medical Center, Boston, Massachusetts, USA
| | - Vipul Chitalia
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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9
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Cohen-Bucay A, Francis JM, Gordon CE. Timing of hepatitis C virus infection treatment in kidney transplant candidates. Hemodial Int 2019; 22 Suppl 1:S61-S70. [PMID: 29694723 DOI: 10.1111/hdi.12643] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Hepatitis C virus (HCV) infection is prevalent in patients with kidney disease including transplant candidates and recipients. It is associated with increased morbidity and mortality in end-stage renal disease patients and also increases the risk of allograft rejection and decreases allograft and patient survival post-transplant. Newly developed direct acting antivirals have revolutionized the way HCV is treated. Whether patients are treated before or after kidney transplantation, the cure rates with direct acting antivirals are >90%. Great debate has formed revolving the optimal timing to treat kidney transplant candidates. On the one hand, treatment before transplantation decreases early post-transplant complications related to HCV. On the other, postponing treatment until after transplantation opens the possibility of transplanting a kidney from a HCV positive donor, which is associated with shorter waiting time and improved organ utilization by expanding the organ donor pool. Most patients living in an area where waiting time is reduced by accepting an HCV positive kidney would benefit by the strategy of treatment post-transplantation, but this decision needs to be individualized in a patient-by-patient basis given that there are special circumstances (i.e., severe HCV-related extrahepatic manifestations, availability of live donors, etc.) in which treatment before transplant might be preferred.
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Affiliation(s)
- Abraham Cohen-Bucay
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA.,Division of Nephrology and Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
| | - Craig E Gordon
- Renal Section, Boston University Medical Center, Boston, Massachusetts, USA
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10
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Ortiz GA, Trivedi HD, Nader C. Pharmacokinetics and drug interactions of medications used to treat hepatitis C virus infection in the setting of chronic kidney disease and kidney transplantation. Hemodial Int 2019; 22 Suppl 1:S22-S35. [PMID: 29694720 DOI: 10.1111/hdi.12648] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Hepatitis C infection in patients with chronic kidney disease or kidney transplant carries higher morbidity and mortality compared to noninfected patients. Historically, patients with advanced kidney disease and kidney transplant recipients were undertreated given the multiple adverse effects and limited efficacy of interferon-based therapies for chronic hepatitis C. The development of direct-acting antivirals in the past few years has opened an unprecedented opportunity for treating these populations. However, the impaired renal clearance of some of these medications in patients with kidney disease, and the potential interactions of antiviral therapies with immunosuppressants after kidney transplantation, present some challenges in choosing the proper regimen. This review provides an overview of the essential pharmacokinetics and drug interactions of relevant antiviral therapies in the treatment of chronic hepatitis C in patients with advanced kidney disease and after kidney transplantation.
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Affiliation(s)
- Guillermo A Ortiz
- Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
| | - Hirsh D Trivedi
- Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Claudia Nader
- Division of Infectious Diseases, Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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11
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Sise ME, Chute DF, Gustafson JL, Wojciechowski D, Elias N, Chung RT, Williams WW. Transplantation of hepatitis C virus infected kidneys into hepatitis C virus uninfected recipients. Hemodial Int 2019; 22 Suppl 1:S71-S80. [PMID: 29694722 DOI: 10.1111/hdi.12650] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Long wait times for kidney transplant and the high risk of mortality on dialysis have prompted investigation into strategies to increase organ allocation and decrease discard rates of potentially viable kidneys. Organs from hepatitis C virus (HCV) antibody positive donors are often rejected; nearly 500 HCV-infected kidneys are discarded annually in the United States. Due the opioid epidemic, the number of HCV-infected donors has increased because of a rise in both new HCV infections and drug-related deaths. In the past 5 years, HCV has been transformed into a curable illness with direct-acting antiviral therapies (DAAs) that are effective in >95% of patients treated and are extremely well tolerated. Recent data has shown several direct-acting antiviral combinations are safe and effective after kidney transplant, and can achieve the same high cure rate seen in the general population and without increasing the rate of acute rejection. Because of this, strategies to decrease discard of HCV-infected organs have been devised. Two recent studies have transplanted HCV-uninfected dialysis patients with kidneys from donors actively infected with HCV; recipients were treated with DAA in the peri-transplant period. More research is needed to determine the safety and efficacy of this approach, but it has the potential to dramatically increase the donor pool of available kidneys, shorten waitlist times and ultimately decreases mortality in patients waiting for kidney transplant.
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Affiliation(s)
- Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Donald F Chute
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jenna L Gustafson
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - David Wojciechowski
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Nahel Elias
- Department of Transplant Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Winfred W Williams
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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12
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Abstract
Kidney transplantation (KT) is the most effective way to decrease the high morbidity and mortality of patients with end-stage renal disease. However, KT does not completely reverse the damage done by years of decreased kidney function and dialysis. Furthermore, new offending agents (in particular, immunosuppression) added in the post-transplant period increase the risk of complications. Cardiovascular (CV) disease, the leading cause of death in KT recipients, warrants pre-transplant screening based on risk factors. Nevertheless, the screening methods currently used have many shortcomings and a perfect screening modality does not exist. Risk factor modification in the pre- and post-transplant periods is of paramount importance to decrease the rate of CV complications post-transplant, either by lifestyle modification (for example, diet, exercise, and smoking cessation) or by pharmacological means (for example, statins, anti-hyperglycemics, and so on). Post-transplantation diabetes mellitus (PTDM) is a major contributor to mortality in this patient population. Although tacrolimus is a major contributor to PTDM development, changes in immunosuppression are limited by the higher risk of rejection with other agents. Immunosuppression has also been implicated in higher risk of malignancy; therefore, proper cancer screening is needed. Cancer immunotherapy is drastically changing the way certain types of cancer are treated in the general population; however, its use post-transplant is limited by the risk of allograft rejection. As expected, higher risk of infections is also encountered in transplant recipients. When caring for KT recipients, special attention is needed in screening methods, preventive measures, and treatment of infection with BK virus and cytomegalovirus. Hepatitis C virus infection is common in transplant candidates and in the deceased donor pool; however, newly developed direct-acting antivirals have been proven safe and effective in the pre- and post-transplant periods. The most important and recent developments on complications following KT are reviewed in this article.
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Affiliation(s)
- Abraham Cohen-Bucay
- Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico.,Nephrology Department, American British Cowdray Medical Center, Mexico City, 05300, Mexico
| | - Craig E Gordon
- Division of Nephrology, Tufts Medical Center, Boston, MA, 02111, USA
| | - Jean M Francis
- Renal Section, Boston University Medical Center, Boston, MA, 02118, USA
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13
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Race, Risk, and Willingness of End-Stage Renal Disease Patients Without Hepatitis C Virus to Accept an HCV-Infected Kidney Transplant. Transplantation 2019; 102:e163-e170. [PMID: 29346260 DOI: 10.1097/tp.0000000000002099] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Despite effective antiviral treatment, hundreds of kidneys from deceased donors with hepatitis C virus (HCV) are discarded annually. Little is known about the determinants of willingness to accept HCV-infected kidneys among HCV-negative patients. METHODS At 2 centers, 189 patients undergoing initial or reevaluation for transplant made 12 hypothetical decisions about accepting HCV-infected kidneys in which we systematically varied expected HCV cure rate, allograft quality, and wait time for an uninfected kidney. RESULTS Only 29% of the participants would accept an HCV-infected kidney under all scenarios, whereas 53% accepted some offers and rejected others, and 18% rejected all HCV-infected kidneys. Higher cure rate (odds ratio [OR], 3.49; 95% confidence interval [CI], 2.33-5.24 for 95% vs 75% probability of HCV cure), younger donor (OR, 2.34; 95% CI, 1.91-2.88 for a 20-year-old vs a 60-year-old hypertensive donor), and longer wait for an uninfected kidney (OR, 1.43; 95% CI, 1.22-1.67 for 5 years vs 2 years) were associated with greater willingness to accept an HCV-infected kidney. Black race modified the effect of HCV cure rate, such that willingness to accept a kidney increased less for blacks versus whites as the cure rate improved. Patients older than 60 years and prior kidney recipients showed greater willingness to accept an HCV-infected organ. CONCLUSIONS Most patients will consider an HCV-infected kidney in some situations. Future trials using HCV-infected kidneys may enhance enrollment by targeting older patients and prior transplant recipients, but centers should anticipate that black patients' acceptance of HCV-infected kidneys will be reduced compared with white patients.
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14
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Sawinski D, Forde KA, Wyatt CM. New Treatment Options for Hepatitis C Virus Infection in End-Stage Kidney Disease: To Treat or Not to Treat. Am J Kidney Dis 2018; 72:7-9. [DOI: 10.1053/j.ajkd.2018.01.049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 01/30/2018] [Indexed: 12/26/2022]
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15
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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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16
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Chute DF, Sise ME. Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010-2016. Am J Nephrol 2018; 47:84-93. [PMID: 29439266 DOI: 10.1159/000486516] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/19/2017] [Indexed: 01/18/2023]
Abstract
BACKGROUND The opioid crisis has led to a dramatic increase in the number of drug overdose deaths in the United States. Little is known about the effect of the opioid crisis on the kidney transplant donor pool, particularly on hepatitis C virus (HCV)-infected donors. METHODS This is a retrospective analysis of the data from the Organ Procurement and Transplantation Network from 2010 to 2016. We determined the changes in characteristics of kidney transplant donors and evaluated which changes may be directly related to the opioid crisis. RESULTS Between 2010 and 2016, we found a 26% increase in overall donors, including a 277% increase in the number of donors who died from drug overdose. Nineteen percent of donors who died of drug overdose had HCV infection. Donors who die from drug overdose and donors with HCV infection are younger, less likely to have diabetes or hypertension, and have favorable kidney donor profile index scores compared to average donors. Despite these favorable characteristics, HCV-infected donors appear to be notably underutilized, with substantially lower kidneys per donor being transplanted compared to HCV uninfected donors. CONCLUSION The opioid crisis in the United States has substantially altered the kidney donor pool. Strategies to increase utilization of all potentially viable kidneys for transplant are needed, particularly in this era of new, highly effective, direct-acting antiviral therapy for HCV infection.
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Affiliation(s)
- Donald F Chute
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Meghan E Sise
- Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
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17
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Chute DF, Chung RT, Sise ME. Direct-acting antiviral therapy for hepatitis C virus infection in the kidney transplant recipient. Kidney Int 2018; 93:560-567. [PMID: 29325996 DOI: 10.1016/j.kint.2017.10.024] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 09/12/2017] [Accepted: 10/05/2017] [Indexed: 12/26/2022]
Abstract
Hepatitis C virus infection (HCV) is a common comorbidity in patients who have undergone kidney transplantation and is associated with increased morbidity and mortality compared with recipients who do not have chronic HCV infection. Because interferon-α-based therapies can precipitate acute rejection, they are relatively contraindicated after kidney transplantation. Thus, the majority of kidney transplant recipients with HCV remain untreated. There are now all-oral, interferon-free direct-acting antiviral therapies for HCV infection that are extremely effective and well tolerated in the general population. Recent reports in the literature demonstrate that direct-acting antiviral therapies effectively cured HCV in 406 of 418 kidney transplant recipients (97%); the majority were treated with sofosbuvir-based regimens. Smaller numbers of kidney transplant recipients have been treated with paritaprevir-ritonavir, ombitasvir and dasabuvir, elbasvir-grazoprevir, or glecaprevir-pibrentasvir with excellent success. Direct-acting antiviral therapies were well tolerated and did not increase the rate of acute rejection. The latest advances include approval of regimens that can treat patients with advanced allograft dysfunction (eGFR < 30 ml/min per 1.73 m2) and "pan-genotypic" regimens that have activity against all 6 major genotypes of HCV. This review summarizes what is known about the epidemiology of HCV infection in kidney transplant recipients, and presents the landscape of direct-acting antiviral therapies and areas in need of further investigation.
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Affiliation(s)
- Donald F Chute
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Raymond T Chung
- Department of Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA.
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18
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Gupta G, Kang L, Yu JW, Limkemann AJ, Garcia V, Bandyopadhyay D, Kumar D, Fattah H, Levy M, Cotterell AH, Sharma A, Bhati C, Reichman T, King AL, Sterling R. Long-term outcomes and transmission rates in hepatitis C virus-positive donor to hepatitis C virus-negative kidney transplant recipients: Analysis of United States national data. Clin Transplant 2017; 31. [DOI: 10.1111/ctr.13055] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2017] [Indexed: 12/31/2022]
Affiliation(s)
- Gaurav Gupta
- Division of Nephrology; Virginia Commonwealth University; Richmond VA USA
| | - Le Kang
- Department of Biostatistics; Virginia Commonwealth University; Richmond VA USA
| | - Jonathan W. Yu
- Department of Biostatistics; Virginia Commonwealth University; Richmond VA USA
| | | | - Victoria Garcia
- Department of Biostatistics; Virginia Commonwealth University; Richmond VA USA
| | | | - Dhiren Kumar
- Division of Nephrology; Virginia Commonwealth University; Richmond VA USA
| | - Hasan Fattah
- Division of Nephrology; Virginia Commonwealth University; Richmond VA USA
| | - Marlon Levy
- Department of Surgery; Virginia Commonwealth University; Richmond VA USA
| | | | - Amit Sharma
- Department of Surgery; Virginia Commonwealth University; Richmond VA USA
| | - Chandra Bhati
- Department of Surgery; Virginia Commonwealth University; Richmond VA USA
| | - Trevor Reichman
- Department of Surgery; Virginia Commonwealth University; Richmond VA USA
| | - Anne L. King
- Division of Nephrology; Virginia Commonwealth University; Richmond VA USA
| | - Richard Sterling
- Section of Hepatology; Virginia Commonwealth University; Richmond VA USA
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19
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Wong RJ, Saab S, Ahmed A. Extrahepatic Manifestations of Hepatitis C Virus After Liver Transplantation. Clin Liver Dis 2017; 21:595-606. [PMID: 28689596 DOI: 10.1016/j.cld.2017.03.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains a leading cause of chronic liver disease in the United States. Although the hepatic impact of chronic HCV leading to cirrhosis and the need for liver transplantation is paramount, the extrahepatic manifestations of chronic HCV infection are equally important. In particular, a better understanding of the prevalence and impact of extrahepatic manifestations of chronic HCV infection in the post-liver transplant setting relies on understanding the interplay between the effects of chronic HCV infection in a posttransplant environment characterized by strong immunosuppression and the associated risks of this milieu.
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Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, 1411 East 31st Street, Highland Hospital - Highland Care Pavilion 5th Floor, Oakland, CA 94602, USA.
| | - Sammy Saab
- Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, 200 UCLA Medical Plaza, Suite 214, Los Angeles, CA 90095, USA; Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, 200 UCLA Medical Plaza, Suite 214, Los Angeles, CA 90095, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite # 210, Palo Alto, CA 94304, USA
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20
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Shah NJ, Russo MW. Is it time to rethink combined liver-kidney transplant in hepatitis C patients with advanced fibrosis? World J Hepatol 2017; 9:288-292. [PMID: 28261386 PMCID: PMC5316849 DOI: 10.4254/wjh.v9.i5.288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 12/04/2016] [Accepted: 12/19/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To reduce hepatic and extrahepatic complications of chronic hepatitis C in kidney transplant recipients.
METHODS We conducted a systematic review of kidney only transplant in patients with hepatitis C and advanced fibrosis.
RESULTS The 5 year patient survival of kidney transplant recipients with and without hepatitis C cirrhosis ranged from 31% to 90% and 85% to 92%, respectively. Hepatitis C kidney transplant recipients had lower 10-year survival when compared to hepatitis B patients, 40% and 90% respectively. There were no studies that included patients with virologic cure prior to kidney transplant that reported post-kidney transplant outcomes. There were no studies of direct acting antiviral therapy and effect on patient or graft survival after kidney transplantation.
CONCLUSION Data on kidney transplant only in hepatitis C patients that reported inferior outcomes were prior to the development of potent direct acting antiviral. With the development of potent directing acting antiviral therapy for hepatitis C with high cure rates studies are needed to determine if patients with hepatitis C, including those with advanced fibrosis, can undergo kidney transplant alone with acceptable long term outcomes.
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21
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Mak SK, Sin HK, Lo KY, Lo MW, Chan SF, Lo KC, Wong YY, Ho LY, Wong PN, Wong AKM. Treatment of HCV in renal transplant patients with peginterferon and ribavirin: long-term follow-up. Clin Exp Nephrol 2017; 21:764-770. [PMID: 28083764 DOI: 10.1007/s10157-016-1364-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 11/23/2016] [Indexed: 11/24/2022]
Abstract
BACKGROUND In addition to the observation of an increased viremia among patients with chronic hepatitis C virus (HCV) infection who undergo renal transplantation, fibrosis and necroinflammatory activity have been noted to worsen comparing pre- and post-renal transplantation liver biopsies in some of these patients. Apart from the reported reduced patient and allograft survival rates, post-transplant diabetes mellitus, de novo glomerulonephritis, and an increased overall risk of infection have been observed. However, antiviral therapy for HCV is generally considered contraindicated among patients with solid organ transplants, with the main worry being the risk of acute rejection in relation to the use of interferon. We reported the long-term outcome of four renal transplant patients with chronic HCV infection who received peginterferon-based therapy. METHODS We collected the long-term follow-up data of four patients who completed the therapy with peginterferon in combination with ribavirin. Two of them had renal impairment at baseline. RESULTS With treatment, they had a significant improvement in terms of serum liver transaminase level, and two patients achieved the early virological response and the other two rapid virological response. All four patients achieved sustained virological response, with neither HCV flare up nor renal dysfunction during follow-up for a mean duration of 74.3 months after therapy. CONCLUSIONS These results suggest that sustained HCV virological response may be achieved without allograft dysfunction, in selected renal transplant patients using a peginterferon-based therapy.
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Affiliation(s)
- Siu-Ka Mak
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China.
| | - Ho-Kwan Sin
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Kin-Yee Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Man-Wai Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Shuk-Fan Chan
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Kwok-Chi Lo
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Yuk-Yi Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Lo-Yi Ho
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Ping-Nam Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
| | - Andrew K M Wong
- Renal Unit, Department of Medicine and Geriatrics, Kwong Wah Hospital, 25 Waterloo Road, Kowloon, Hong Kong SAR, China
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22
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Miyazaki R, Miyagi K. Successful treatment of chronic hepatitis C virus genotype 1b infection of a patient with compensated cirrhosis after renal transplantation using daclatasvir-asunaprevir combination therapy: a case report and literature review. RENAL REPLACEMENT THERAPY 2016. [DOI: 10.1186/s41100-016-0075-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Carrier P, Essig M, Debette-Gratien M, Sautereau D, Rousseau A, Marquet P, Jacques J, Loustaud-Ratti V. Anti-hepatitis C virus drugs and kidney. World J Hepatol 2016; 8:1343-1353. [PMID: 27917261 PMCID: PMC5114471 DOI: 10.4254/wjh.v8.i32.1343] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Revised: 07/08/2016] [Accepted: 09/18/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients (transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.
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24
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Sasaki R, Kanda T, Yasui S, Haga Y, Nakamura M, Yamato M, Wu S, Nakamoto S, Arai M, Mikami S, Miyauchi H, Matsubara H, Yokosuka O. Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation. Case Rep Gastroenterol 2016; 10:248-56. [PMID: 27462193 PMCID: PMC4939684 DOI: 10.1159/000445374] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatitis C virus (HCV) infection leads to acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following kidney transplantation, HCV increases the risk of graft loss and patient mortality compared with uninfected patients. The achievement of a sustained virological response with antiviral therapy improves survival and diminishes the risk of hepatic decompensation in HCV patients after a kidney transplant. It has been reported that direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of HCV in patients who are liver transplant recipients. In the present study, we investigated HCV eradication via interferon-free therapies with DAAs in two HCV patients with advanced liver fibrosis following renal transplantation. In both cases, the interferon-free regimens with DAAs were effective in eradicating HCV in the patients after kidney transplantation. No adverse events caused by interferon were identified with the exception of anemia. Interferon-free regimens with DAAs for recurrent HCV in patients following kidney transplantation are relatively safe and effective. However, attention should be focused on anemia during these treatments.
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Affiliation(s)
- Reina Sasaki
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shin Yasui
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Yuki Haga
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Masato Nakamura
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Mutsumi Yamato
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan; Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Makoto Arai
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Shigeru Mikami
- Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan
| | - Hideaki Miyauchi
- Department of Frontier Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan
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25
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Batchelder AW, Peyser D, Nahvi S, Arnsten JH, Litwin AH. "Hepatitis C treatment turned me around:" Psychological and behavioral transformation related to hepatitis C treatment. Drug Alcohol Depend 2015; 153:66-71. [PMID: 26096534 PMCID: PMC4759650 DOI: 10.1016/j.drugalcdep.2015.06.007] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 06/02/2015] [Accepted: 06/03/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatitis C (HCV) is a significant public health problem that primarily affects current and former substance users. However, individuals with a history of substance use are less likely to have access to or engage in HCV care. Psychological and behavioral barriers prevent many HCV-infected individuals from initiating or engaging in HCV treatment. This study aimed to investigate the psychological and behavioral experiences of current and former substance users receiving HCV treatment within a combined methadone and primary care clinic in the United States. METHODS We conducted 31 semi-structured qualitative interviews with opioid-dependent adults enrolled in an integrated HCV treatment program within a methadone maintenance clinic in the Bronx, NY. We used thematic analysis, informed by grounded theory, and inquired about perceptions of HCV before and after initiating HCV treatment, reasons for initiating HCV treatment, and the decision to participate in individual versus group HCV treatment. RESULTS Participants described psychological and behavioral transformation over the course of HCV treatment. These included reductions in internalized stigma and shame related to HCV and addiction, increases in HCV disclosure and self-care, reductions in substance use, and new desire to help others who are living with HCV. CONCLUSIONS Integrating HCV treatment with methadone maintenance has the potential to create psychological and behavioral transformations among substance using adults, including reductions in HCV- and addiction-related shame and improvements in overall self-care.
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Affiliation(s)
- AW Batchelder
- Einstein-Montefiore Division of General Internal Medicine, Albert Einstein College of Medicine, 3300 Kossuth Avenue, Bronx, NY 10467, USA,Osher Center for Integrative Medicine, University of San Francisco, San Francisco, 1545 Divisadero Street, 3rd Floor, San Francisco, CA 94115, USA
| | - D Peyser
- Einstein-Montefiore Division of General Internal Medicine, Albert Einstein College of Medicine, 3300 Kossuth Avenue, Bronx, NY 10467, USA; Center for Alcohol Studies, Rutgers University, 607 Allison Road, Piscataway, NJ 08854, USA.
| | - S Nahvi
- Einstein-Montefiore Division of General Internal Medicine, Albert Einstein College of Medicine, 3300 Kossuth Avenue, Bronx, NY 10467, USA.
| | - JH Arnsten
- Einstein-Montefiore Division of General Internal Medicine, Albert Einstein College of Medicine, 3300 Kossuth Avenue, Bronx, NY 10467, USA
| | - AH Litwin
- Einstein-Montefiore Division of General Internal Medicine, Albert Einstein College of Medicine, 3300 Kossuth Avenue, Bronx, NY 10467, USA
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Aguirre Valadez J, García Juárez I, Rincón Pedrero R, Torre A. Management of chronic hepatitis C virus infection in patients with end-stage renal disease: a review. Ther Clin Risk Manag 2015; 11:329-38. [PMID: 25767389 PMCID: PMC4354469 DOI: 10.2147/tcrm.s74282] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Infection with hepatitis C virus (HCV) is highly prevalent in chronic kidney disease (CKD) patients, mainly in those on hemodialysis (HD). The seroprevalence of HCV in developing countries ranges between 7% and 40%. Risk factors for this infection in the CKD population include the number of blood transfusions, duration of end-stage renal disease (ESRD), and prevalence of HCV in HD. Chronic HCV infection in patients with ESRD is associated with an increase in morbidity and mortality in the pre and post kidney transplant periods. The increase in mortality is directly associated with liver complications and an elevated cardiovascular risk in HCV-infected patients on hemodialysis. Antiviral treatment may improve the prognosis of patients with HCV, and standard interferon remains the cornerstone of treatment. Treatment of HCV in patients with CKD is complex, but achieving a sustained viral response may decrease the frequency of complications after transplantation. It appears that HCV-infected patients who remain on maintenance dialysis are at increased risk of death compared with HCV patients undergoing renal transplantation.
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Affiliation(s)
- Jonathan Aguirre Valadez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Ignacio García Juárez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Rodolfo Rincón Pedrero
- Department of Nephrology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
| | - Aldo Torre
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico
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27
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Bunchorntavakul C, Maneerattanaporn M, Chavalitdhamrong D. Management of patients with hepatitis C infection and renal disease. World J Hepatol 2015; 7:213-25. [PMID: 25729476 PMCID: PMC4342603 DOI: 10.4254/wjh.v7.i2.213] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 11/10/2014] [Accepted: 11/17/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is associated with more rapid liver disease progression and reduced renal graft and patients' survival following kidney transplantation. Evaluations and management of HCV in patients with renal disease are challenging. The pharmacokinetics of interferons (IFN), ribavirin (RBV) and some direct acting antiviral (DAA), such as sofosbuvir, are altered in patients with ESRD. With dose adjustment and careful monitoring, treatment of HCV in patients with ESRD can be associated with sustained virological response (SVR) rates nearly comparable to that of patients with normal renal function. DAA-based regimens, especially the IFN-free and RBV-free regimens, are theoretically preferred for patients with ESRD and KT in order to increase SVR rates and to reduce treatment side effects. However, based on the data for pharmacokinetics, dosing safety and efficacy of DAA for patients with severe renal impairment are lacking. This review will be focused on the evaluations, available pharmacologic data, and management of HCV in patients with severe renal impairment, patients who underwent KT, and those who suffered from HCV-related renal disease, according to the available treatment options, including DAA.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Chalermrat Bunchorntavakul, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok 10400, Thailand
| | - Monthira Maneerattanaporn
- Chalermrat Bunchorntavakul, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok 10400, Thailand
| | - Disaya Chavalitdhamrong
- Chalermrat Bunchorntavakul, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok 10400, Thailand
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28
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Azmi AN, Tan SS, Mohamed R. Hepatitis C and kidney disease: An overview and approach to management. World J Hepatol 2015; 7:78-92. [PMID: 25624999 PMCID: PMC4295197 DOI: 10.4254/wjh.v7.i1.78] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Revised: 10/13/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C infection and chronic kidney disease are major health burden worldwide. Hepatitis C infection is associated with a wide range of extra-hepatic manifestations in various organs including the kidneys. A strong association between hepatitis C and chronic kidney disease has come to light. Hemodialysis in supporting the end stage renal disease patients unfortunately carries a risk for hepatitis C infection. Despite much improvement in the care of this group of patients, the prevalence of hepatitis C infection in hemodialysis patients is still higher than the general population. Hepatitis C infection has a negative effect on the survival of hemodialysis and renal transplant patients. Treatment of hepatitis C in end stage renal disease patients using conventional or pegylated interferon with or without ribavirin remains a clinical challenge with low response rate, high dropout rate due to poor tolerability and many unmet needs. The approval of new direct acting antiviral agents for hepatitis C may dramatically change the treatment approach in hepatitis C infected patients with mild to moderate renal impairment. However it remains to be confirmed if the newer Hepatitis C therapies are safe in individuals with severe renal impairment. This review article discusses the relationship between hepatitis C and chronic kidney disease, describe the various types of renal diseases associated with hepatitis C and the newer as well as the existing treatments for hepatitis C in the context of this subpopulation of hepatitis C patients.
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Carvalho-Filho RJ, Feldner ACCA, Silva AEB, Ferraz MLG. Management of hepatitis C in patients with chronic kidney disease. World J Gastroenterol 2015; 21:408-422. [PMID: 25593456 PMCID: PMC4292272 DOI: 10.3748/wjg.v21.i2.408] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 09/07/2014] [Accepted: 12/08/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is highly prevalent among chronic kidney disease (CKD) subjects under hemodialysis and in kidney transplantation (KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on management and treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon (PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus.
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Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C virus infection and kidney transplantation in 2014: what's new? Am J Transplant 2014; 14:2206-20. [PMID: 25091274 DOI: 10.1111/ajt.12835] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 05/15/2014] [Accepted: 05/16/2014] [Indexed: 01/25/2023]
Abstract
Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.
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Affiliation(s)
- S Baid-Agrawal
- Department of Nephrology and Medical Intensive Care, Campus Virchow-Klinikum, Charité Universitaetsmedizin Berlin, Berlin, Germany
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