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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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Reese PP, Diamond JM, Goldberg DS, Potluri V, Prenner S, Blumberg EA, Van Deerlin VM, Reddy KR, Mentch H, Hasz R, Woodards A, Gentile C, Smith J, Bermudez C, Crespo MM. The SHELTER Trial of Transplanting Hepatitis C Virus-Infected Lungs Into Uninfected Recipients. Transplant Direct 2023; 9:e1504. [PMID: 37389016 PMCID: PMC10306429 DOI: 10.1097/txd.0000000000001504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 04/11/2023] [Accepted: 05/05/2023] [Indexed: 07/01/2023] Open
Abstract
SHELTER is a trial of transplanting lungs from deceased donors with hepatitis C virus (HCV) infection into HCV-negative candidates (sponsor: Merck; NCT03724149). Few trials have reported outcomes using thoracic organs from HCV-RNA+ donors and none have reported quality of life (QOL). Methods This study is a single-arm trial of 10 lung transplants at a single center. Patients were included who were between 18 and 67 y of age and waitlisted for lung-only transplant. Patients were excluded who had evidence of liver disease. Primary outcome was HCV cure (sustained virologic response 12 wk after completing antiviral therapy). Recipients longitudinally reported QOL using the validated RAND-36 instrument. We also applied advanced methods to match HCV-RNA+ lung recipients to HCV-negative lung recipients in a 1:3 ratio at the same center. Results Between November 2018 and November 2020, 18 patients were consented and opted-in for HCV-RNA+ lung offers in the allocation system. After a median of 37 d (interquartile range [IQR], 6-373) from opt-in, 10 participants received double lung transplants. The median recipient age was 57 y (IQR, 44-67), and 7 recipients (70%) had chronic obstructive pulmonary disease. The median lung allocation score at transplant was 34.3 (IQR, 32.7-86.9). Posttransplant, 5 recipients developed primary graft dysfunction grade 3 on day 2 or 3, although none required extracorporeal membrane oxygenation. Nine patients received elbasvir/grazoprevir, whereas 1 patient received sofosbuvir/velpatasvir. All 10 patients were cured of HCV and survived to 1 y (versus 83% 1-y survival among matched comparators). No serious adverse events were found to be related to HCV or treatment. RAND-36 scores showed substantial improvement in physical QOL and some improvement in mental QOL. We also examined forced expiratory volume in 1 s-the most important lung function parameter after transplantation. We detected no clinically important differences in forced expiratory volume in 1 s between the HCV-RNA+ lung recipients versus matched comparators. Conclusions SHELTER adds important evidence regarding the safety of transplanting HCV-RNA+ lungs into uninfected recipients and suggests QOL benefits.
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Affiliation(s)
- Peter P. Reese
- Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology and Bioinformatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Joshua M. Diamond
- Division of Pulmonary Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - David S. Goldberg
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
| | - Vishnu Potluri
- Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Department of Biostatistics, Epidemiology and Bioinformatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Stacey Prenner
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Emily A. Blumberg
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Vivianna M. Van Deerlin
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - K. Rajender Reddy
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Heather Mentch
- Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | | | | | - Caren Gentile
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Jennifer Smith
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Christian Bermudez
- Division of Cardiothoracic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Maria M. Crespo
- Division of Pulmonary Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Jung WS, Kuh JH, Lim L, Yoo HK, Ju JW, Lee HJ, Kim WH. T-cell specific antibody induction versus corticosteroid induction immunosuppression for liver transplant recipients: a meta-analysis. Sci Rep 2023; 13:6951. [PMID: 37117258 PMCID: PMC10147598 DOI: 10.1038/s41598-023-32972-z] [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: 02/03/2023] [Accepted: 04/05/2023] [Indexed: 04/30/2023] Open
Abstract
Corticosteroids remain the mainstay of immunosuppression for liver transplant recipients despite several serious complications including infection, hepatitis C virus (HCV) recurrence, diabetes mellitus (DM), and hypertension. We attempted to compare the safety and efficacy of T-cell specific antibody induction with complete corticosteroid avoidance. We searched MEDLINE, EMBASE, and Cochrane central library. Randomized controlled trials comparing T-cell specific antibody induction with corticosteroid induction immunosuppression were included. Our primary outcome was the incidence of biopsy-proven acute rejection. Eleven trials involving 1683 patients were included. The incidence of acute rejection was not significantly different between the antibody and steroid induction groups (risk ratio [RR] 0.85, 95% confidence interval [CI] 0.72, 1.01, P = 0.06, I2 = 0%). However, T-cell specific antibody induction significantly reduced the risk of cytomegalovirus infection (RR 0.48, 95% CI 0.33, 0.70, P = 0.0002, I2 = 3%), HCV recurrence (RR 0.89, 95% CI 0.80, 0.99, P = 0.03, I2 = 0%), DM (RR 0.41, 95% CI 0.32, 0.54, P < 0.0001, I2 = 0%) and hypertension (RR 0.71, 95% CI 0.55, 0.90, P = 0.005, I2 = 35%). Trial sequential analysis for acute rejection showed that the cumulative z-curve did not cross the Trial sequential boundary and the required information size was not reached. T-cell specific antibody induction compared to corticosteroid induction seems to significantly reduce opportunistic infections including cytomegalovirus infection and HCV recurrence and metabolic complications including DM and hypertension. However, given the insufficient study power, low quality of evidence, and heterogeneous immunosuppressive regimens, our results should be cautiously appreciated.
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Affiliation(s)
- Woo-Seok Jung
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jae Hee Kuh
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Leerang Lim
- Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Hae Kyung Yoo
- Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jae-Woo Ju
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Ho-Jin Lee
- Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Won Ho Kim
- Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
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Saracco M, Tandoi F, Maletta F, Balagna R, Romagnoli R, Martini S. Early post-liver transplant use of direct-acting antivirals in naive and NS5A inhibitor-experienced HCV patients. J Viral Hepat 2023; 30:201-208. [PMID: 36478502 DOI: 10.1111/jvh.13782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/26/2022] [Accepted: 11/30/2022] [Indexed: 02/16/2023]
Abstract
Direct-acting antiviral drugs (DAA) are safe and effective in the HCV population. However, in patients with decompensated cirrhosis and/or active hepatocellular carcinoma or relapse to NS5A inhibitors, response rates are lower and DAA therapy must be postponed until after liver transplant in an era of organ shortage and suboptimal donors. We aimed to assess the prevalence of patients still HCV infected at time of transplantation over the last 3 years in our Center and describe the safety and efficacy of DAA therapy started as soon as possible after surgery. We enrolled all HCV viraemic patients transplanted in our Centre from January 2019 to March 2022. The follow-up was closed in July 2022. Among 490 liver transplants, 49 (10%) patients were still HCV viraemic at operation, 43 naive to DAA and 6 were NS5A-experienced. Median donor age was 64 years; donor risk index was 1.8. In naive patients, sofosbuvir/velpatasvir was started after a median time of 1 day from surgery, while in NS5A-experienced sofosbuvir/velpatasvir/voxilaprevir after 14.5 days (p = .001). Response rate was 98%. 1 NS5A-experienced patient experienced acute cholestatic hepatitis which promptly reverted after permanent DAA discontinuation. Hence, very early post-liver transplant HCV eradication was safe and effective thanks to a close teamwork which involved anaesthesiologists, transplant surgeons and hepatologists.
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Affiliation(s)
- Margherita Saracco
- Gastrohepatology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Francesco Tandoi
- Liver Transplantation Center and General Surgery 2U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Francesca Maletta
- Pathology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Roberto Balagna
- Anesthesia and Intensive Care Unit 2, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Renato Romagnoli
- Liver Transplantation Center and General Surgery 2U, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
| | - Silvia Martini
- Gastrohepatology Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy
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Ganapathi AM, Whitson BA, Heh V, Keller BC, Smith SA, Mokadam NA, Henn MC. Donor and Recipient Hepatitis C Status Does Not Affect Rejection in Thoracic Transplantation. Ann Thorac Surg 2023; 115:221-230. [PMID: 35940315 DOI: 10.1016/j.athoracsur.2022.05.072] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 05/12/2022] [Accepted: 05/28/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Donors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients. METHODS Adults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor-recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used. RESULTS Meeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41). CONCLUSIONS Use of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection.
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Affiliation(s)
- Asvin M Ganapathi
- Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.
| | - Bryan A Whitson
- Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Victor Heh
- Section of Biostatistics, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Brian C Keller
- Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Sakima A Smith
- Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Nahush A Mokadam
- Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Matthew C Henn
- Division of Cardiac Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
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Filippidis P, Vionnet J, Manuel O, Mombelli M. Prevention of viral infections in solid organ transplant recipients in the era of COVID-19: a narrative review. Expert Rev Anti Infect Ther 2021; 20:663-680. [PMID: 34854329 DOI: 10.1080/14787210.2022.2013808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION In solid organ transplant (SOT) recipients, viral infections are associated with direct morbidity and mortality and may influence long-term allograft outcomes. Prevention of viral infections by vaccination, antiviral prophylaxis, and behavioral measures is therefore of paramount importance. AREAS COVERED We searched Pubmed to select publications to review current preventive strategies against the most important viral infections in SOT recipients, including SARS-CoV-2, influenza, CMV, and other herpesvirus, viral hepatitis, measles, mumps, rubella, and BK virus. EXPERT OPINION The clinical significance of the reduced humoral response following mRNA SARS-CoV-2 vaccines in SOT recipients still needs to be better clarified, in particular with regard to the vaccines' efficacy in preventing severe disease. Although a third dose improves immunogenicity and is already integrated into routine practice in several countries, further research is still needed to explore additional interventions. In the upcoming years, further data are expected to better delineate the role of virus-specific cell mediated immune monitoring for the prevention of CMV and potentially other viral diseases, and the role of the letermovir in the prevention of CMV in SOT recipients. Future studies including clinical endpoints will hopefully facilitate the integration of successful new influenza vaccination strategies into clinical practice.
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Affiliation(s)
| | - Julien Vionnet
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland.,Service of Gastroenterology and Hepatology, Lausanne University Hospital, Lausanne, Switzerland
| | - Oriol Manuel
- Service of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland.,Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Matteo Mombelli
- Service of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland.,Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland.,Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
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Cuvelier S, Van Caeseele P, Kadatz M, Peterson K, Sun S, Dodd N, Werestiuk K, Koulack J, Nickerson P, Ho J. Expanding the Deceased Donor Pool in Manitoba Using Hepatitis C-Viremic Donors: Program Report. Can J Kidney Health Dis 2021; 8:20543581211033496. [PMID: 34367648 PMCID: PMC8317248 DOI: 10.1177/20543581211033496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/07/2021] [Indexed: 11/25/2022] Open
Abstract
Purpose of program: The ongoing shortage of organs for transplant combined with Manitoba having the highest prevalence of end-stage renal disease (ESRD) in Canada has resulted in long wait times on the deceased donor waitlist. Therefore, the Transplant Manitoba Adult Kidney Program has ongoing quality improvement initiatives to expand the deceased donor pool. This clinical transplant protocol describes the use of prophylactic pan-genotypic direct-acting anti-viral agents (DAA) for transplanting hepatitis C (HCV)-viremic kidneys (HCV antibody positive/nucleic acid [nucleic acid amplification testing, NAT] positive) to HCV-naïve recipients as routine standard of care. We will evaluate the provincial implementation of this protocol as a prospective observational cohort study. Sources of information: Scoping literature review and key stakeholder engagement with interdisciplinary health care providers and health system leaders/decision markers. Methods: Patients will be screened pre-transplant for eligibility and undergo a multilevel education and consent process to participate in this expanded donor program. Incident adult HCV-naïve recipients of an HCV-viremic kidney transplant will be treated prophylactically with glecaprevir-pibrentasvir with the first dose administered on call to the operation. Glecaprevir-pibrentasvir will be used for 8 weeks with viral monitoring and hepatology follow-up. Primary outcomes are sustained virologic response (SVR) at 12 weeks and the tolerability of DAA therapy. Secondary outcomes within the first year post-transplant are patient and graft survival, graft function, biopsy-proven rejection, HCV transmission to recipient (HCV NAT positive), and HCV nonstructural protein 5A (NS5A) resistance. Safety outcomes within the first year post-transplant include fibrosing cholestatic hepatitis, acute liver failure, primary and secondary DAA treatment failure, HCV transmission to a recipient’s partner, elevated liver enzymes ≥2-fold, abnormal international normalized ratio (INR), angioedema, anaphylaxis, cirrhosis, and hepatocellular carcinoma. Key findings: This program successfully advocated for and obtained hospital formulary, provincial Exceptional Drug Status (EDS), and Non-Insured Health Benefits (NIHB) to provide prophylactic DAA therapy for this indication, and this information may be useful to other provincial transplant organizations seeking to establish an HCV-viremic kidney transplant program with prophylactic DAA drug coverage. Limitations: (1) Patient engagement was not undertaken during the program design phase, but patient-reported experience measures will be obtained for continuous quality improvement. (2) Only standard criteria donors (optimal kidney donor profile index [KDPI] ≤60) will be used. If this approach is safe and feasible, then higher KDPI donors may be included. Implications: The goal of this quality improvement project is to improve access to kidney transplantation for Manitobans. This program will provide prophylactic DAA therapy for HCV-viremic kidney transplant to HCV-naïve recipients as routine standard of care outside a clinical trial protocol. We anticipate this program will be a safe and effective way to expand kidney transplantation from a previously unutilized donor pool.
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Affiliation(s)
- Susan Cuvelier
- Section of Hepatology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada
| | | | - Matthew Kadatz
- Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, Canada
| | - Kathryn Peterson
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Siyao Sun
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Nancy Dodd
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Kim Werestiuk
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada
| | - Joshua Koulack
- Section of Vascular Surgery, Department of Surgery, University of Manitoba, Winnipeg, Canada
| | - Peter Nickerson
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada.,Section of Nephrology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.,Department of Immunology, University of Manitoba, Winnipeg, Canada
| | - Julie Ho
- Transplant Manitoba Adult Kidney Program, Winnipeg, Manitoba, Canada.,Section of Nephrology, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.,Department of Immunology, University of Manitoba, Winnipeg, Canada
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8
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Kauffman-Ortega E, Ruiz-Manriquez J, Olivas-Martinez A, Campos-Murguía A, Flores-García NC, Márquez-Guillén E, López-Yáñez S, Sánchez-Ávila F, Toapanta-Yanchapaxi L, Paez-Zayas VM, García-Juárez I. Direct-Acting Antivirals in the Treatment of Hepatitis C Virus Recurrence after Liver Transplantation: Real-life Experience in a Mexican Cohort. Arch Med Res 2021; 52:713-718. [PMID: 33966917 DOI: 10.1016/j.arcmed.2021.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 03/31/2021] [Accepted: 04/14/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) infection is one of the most frequent causes of liver transplantation (LT) worldwide. Patients with HCV viremia at the time of LT universally develop recurrent HCV in the allograft, leading to accelerated fibrosis and graft loss. Treatment with direct-acting antivirals (DAA) is highly effective and safe in this population. AIM OF THE STUDY To describe the efficacy and safety of DAA in treating post LT HCV recurrence in a Mexican cohort. METHODS We designed a retrospective cohort study that included all LT patients from 2000-2019 with HCV recurrence after LT who received DAA. Clinical and biochemical characteristics were collected from clinical records. Patients who received treatment before LT and those who received interferon-based therapies after LT achieving sustained viral response at 12 weeks were excluded; patients who didn´t complete DAA therapy were eliminated. The primary outcome was SVR-12. RESULTS Fifty-six patients received DAA after the LT with 98% SVR-12. The most frequent genotypes were 1b (54%) and 1a (34%). The most common antiviral scheme used was sofosbuvir/ledipasvir for 12 weeks in 59% of the patients. No severe adverse effects were observed. Ribavirin was used in 82% of the patients, of which 23.9% had adverse effects, mostly mild. The median follow-up after LT was 55 months (IQR 43-51), with a global and graft survival at one and three years of 100%. CONCLUSION In a Mexican cohort, DAA therapy in LT patients with recurrence of HCV infection showed high efficacy and an acceptable safety profile.
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Affiliation(s)
- Eric Kauffman-Ortega
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | - Jesus Ruiz-Manriquez
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | | | - Alejandro Campos-Murguía
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | - Nayelli C Flores-García
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | - Ernesto Márquez-Guillén
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | - Silvia López-Yáñez
- Gastroenterology Social work Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | | | - Liz Toapanta-Yanchapaxi
- Neuromuscular Disease Clinic, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
| | - Victor M Paez-Zayas
- Organ Trasplant Department, Hospital General de México, "Dr. Eduardo Liceaga"
| | - Ignacio García-Juárez
- Hepatology and Liver Transplantation Unit, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México.
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9
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Logan C, Yumul I, Cepeda J, Pretorius V, Adler E, Aslam S, Martin NK. Cost-effectiveness of using hepatitis C viremic hearts for transplantation into HCV-negative recipients. Am J Transplant 2021; 21:657-668. [PMID: 32777173 PMCID: PMC8216294 DOI: 10.1111/ajt.16245] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 07/08/2020] [Accepted: 07/25/2020] [Indexed: 01/25/2023]
Abstract
Outcomes following hepatitis C virus (HCV)-viremic heart transplantation into HCV-negative recipients with HCV treatment are good. We assessed cost-effectiveness between cohorts of transplant recipients willing and unwilling to receive HCV-viremic hearts. Markov model simulated long-term outcomes among HCV-negative patients on the transplant waitlist. We compared costs (2018 USD) and health outcomes (quality-adjusted life-years, QALYs) between cohorts willing to accept any heart and those willing to accept only HCV-negative hearts. We assumed 4.9% HCV-viremic donor prevalence. Patients receiving HCV-viremic hearts were treated, assuming $39 600/treatment with 95% cure. Incremental cost-effectiveness ratios (ICERs) were compared to a $100 000/QALY gained willingness-to-pay threshold. Sensitivity analyses included stratification by blood type or region and potential negative consequences of receipt of HCV-viremic hearts. Compared to accepting only HCV-negative hearts, accepting any heart gained 0.14 life-years and 0.11 QALYs, while increasing costs by $9418/patient. Accepting any heart was cost effective (ICER $85 602/QALY gained). Results were robust to all transplant regions and blood types, except type AB. Accepting any heart remained cost effective provided posttransplant mortality and costs among those receiving HCV-viremic hearts were not >7% higher compared to HCV-negative hearts. Willingness to accept HCV-viremic hearts for transplantation into HCV-negative recipients is cost effective and improves clinical outcomes.
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Affiliation(s)
- Cathy Logan
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego
| | - Ily Yumul
- Division of Cardiology, Department of Medicine, University of Iowa
| | - Javier Cepeda
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego
| | - Victor Pretorius
- Division of Cardiothoracic Surgery, Department of Surgery, University of California San Diego
| | - Eric Adler
- Division of Cardiology, Department of Medicine, University of California San Diego
| | - Saima Aslam
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego
| | - Natasha K Martin
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego
- Population Health Sciences, University of Bristol, UK
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10
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Roche B, Coilly A, Samuel D. Management of Transplant Patients Infected with HCV. HEPATITIS C: CARE AND TREATMENT 2021:153-173. [DOI: 10.1007/978-3-030-67762-6_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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11
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Elzorkany K, Kora MAE, Wahed ASA, Zaghla HES, Zahran AM, Yassein YS, El Naggar AZ, Essa A, Gadallah AA. Assessment of Renal Function in Post-Liver Transplant HCV-Positive Patients Treated with Direct Acting Antivirals. Int J Nephrol Renovasc Dis 2020; 13:351-358. [PMID: 33273842 PMCID: PMC7705253 DOI: 10.2147/ijnrd.s275721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/21/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose Direct acting antiviral agents (DAAs) have greatly improved the clearance of hepatitis C virus (HCV) infection. The effect of DAAs on renal function in post-liver transplant HCV-positive patients remains questionable, especially considering the possibility of drug interactions between immunosuppressants and DAAs. Patients and methods A retrospective observational study included 84 post-liver transplant patients with HCV infection. Patients were divided into two groups: group I received sofosbuvir plus ribavirin for 24 weeks, group II received sofosbuvir plus daclatasvir for 12 weeks. Laboratory data and eGFR were determined before, at the end, and 6 months after completion of treatment. Results The treatment was well tolerated with 100% sustained virologic response (SVR 12). There was no statistically significant difference between the two groups regarding clinical and laboratory data before treatment. Mean eGFR significantly reduced from 87.36 mL/min to 76.16 mL/min in group I (P=0.001). However, within 6 months after treatment, mean eGFR recovered to 81.51 mL/min, which was not significant when compared to baseline eGFR (P=0.09). Mean eGFR in group II showed non-significant change. There were no significant changes in immunosuppressive drug levels and eGFR in either group of patients, who received either ciclosporin or tacrolimus before and at the end of treatment. Conclusion DDAs in post-liver transplant patients with HCV infection were well tolerated and associated with stable renal function. Moreover, sofosbuvir plus daclatasvir regimen showed relatively better renal safety compared to sofosbuvir plus ribavirin.
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Affiliation(s)
- Khaled Elzorkany
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt.,Internal Medicine Department, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mahmoud Abd-Elaziz Kora
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | - Aliaa Sabry Abdel Wahed
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt
| | - Hassan El-Sayed Zaghla
- Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt
| | - Ahmed Mohamed Zahran
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | - Yassein Salah Yassein
- Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
| | | | - Abdallah Essa
- Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt
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Abstract
INTRODUCTION Liver transplantation is a life-changing event for patients and survival following transplantation has improved significantly since the first transplantation in 1967. Following liver transplantation, patients face a unique set of healthcare management decisions including transplantation-specific complications, recurrence of primary liver disease, as well as metabolic and malignancy concerns related to immunosuppression. As more patients with liver disease receive transplantation and live longer, understanding and managing these patients will require not only transplant specialist but also local subspecialist and primary care physicians. AREAS COVERED This review covers common issues related to the management of patients following liver transplantation including immunosuppression, liver allograft dysfunction, metabolic complications, as well as routine health maintenance such as immunizations and cancer screening. EXPERT OPINION Optimizing medical care for patients following liver transplant will benefit from ensuring all providers, not just transplant specialist, have a basic understanding of the common issues encountered in the post-transplant patient. This review provides an overview of common healthcare concerns and management options for patients following liver transplantation.
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Affiliation(s)
- Nicholas Hoppmann
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
| | - Omar Massoud
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham , Birmingham, Alabama, USA
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13
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Aehling NF, Seehofer D, Berg T. [Liver transplantation - current trends]. Dtsch Med Wochenschr 2020; 145:1124-1131. [PMID: 32791547 DOI: 10.1055/a-0982-0737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INDICATION OF TRANSPLANTATION There is an ongoing change in the indications of orthotopic liver transplantation (OLT) with non-alcoholic and alcoholic liver disease and hepatocellular carcinoma (HCC) becoming the main indications whereas the numbers of cirrhosis due to chronic viral hepatitis are declining. 6-MONTH ABSTINENCE RULE: : The directive of the German Federal Medical Association requires absolute abstinence from alcohol for at least 6 months. New data show that patients with severe alcoholic hepatitis for the first time who do not show a response to medical treatment may benefit from OLT. For these patients an individual exception for OLT listing can be requested. HCC BEYOND MILAN CRITERIA New data show that patients with HCC outside the Milan criteria may have a favorable prognosis, which can be comparable to patients with HCC within the Milan criteria, if effective pre-transplant "down-staging" therapies but also alfa fetoprotein levels are taken into consideration. TOO SICK TO TRANSPLANT?: Even patients with decompensated cirrhosis and multi-organ dysfunction, defined as acute-on-chronic liver failure, may undergo OLT successfully with a beneficial long-term prognosis. However, the timeframe to realize OLT is short. ORGAN SHORTAGE OLT using organs from HBV- or HCV-infected patients represents a relevant strategy to mitigate organ shortage and can be safely and effectively be performed due to the excellent therapeutic options against these infections which are available now. In addition, machine perfusion, a novel tool for organ conservation and conditioning, may help preserving organs for transplantation that formerly could not be used.
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Affiliation(s)
- Niklas F Aehling
- Bereich Hepatologie, Medizinische Klinik II, Universitätsklinikum Leipzig
| | - Daniel Seehofer
- Bereich Hepatologie, Medizinische Klinik II, Universitätsklinikum Leipzig
| | - Thomas Berg
- Bereich Hepatologie, Medizinische Klinik II, Universitätsklinikum Leipzig
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Yu ML, Chen PJ, Dai CY, Hu TH, Huang CF, Huang YH, Hung CH, Lin CY, Liu CH, Liu CJ, Peng CY, Lin HC, Kao JH, Chuang WL. 2020 Taiwan consensus statement on the management of hepatitis C: Part (II) special populations. J Formos Med Assoc 2020; 119:1135-1157. [PMID: 32354689 DOI: 10.1016/j.jfma.2020.04.002] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 04/05/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatitis C virus (HCV) infection is a silent killer that leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (HCC). High prevalence of HCV infection has been reported in Taiwan, especially in high-risk populations including people who inject drugs (PWID) and patients requiring dialysis. Besides, certain populations merit special considerations due to suboptimal outcome, potential drug-drug interaction, or possible side effect. Therefore, in the second part of this 2-part consensus, the Taiwan Association for the Study of the Liver (TASL) proposes the treatment recommendations for the special population in order to serve as guidance to optimizing the outcome in the direct-acting antiviral (DAA) era. Special populations include patients with acute or recent HCV infection, previous DAA failure, chronic kidney disease, decompensated cirrhosis, HCC, liver and other solid organ transplantations, receiving an HCV viremic organ, hepatitis B virus (HBV) and HCV dual infection, HCV and human immunodeficiency virus (HIV) coinfection, active tuberculosis infection, PWID, bleeding disorders and hemoglobinopathies, children and adolescents, and pregnancy. Moreover, future perspectives regarding the management of hepatitis C are also discussed and summarized in this consensus statement.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
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15
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Fu H, Dong J, Sun Z, Zhang X, Yu A, Chen G, Li W. Efficacy and safety of sofosbuvir-containing regimens in patients with chronic hepatitis C virus infection after liver transplantation: a meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:648. [PMID: 32566585 PMCID: PMC7290620 DOI: 10.21037/atm-20-3074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Background This meta-analysis evaluated the efficacy and safety of a sofosbuvir (SOF)-containing regimen in patients with hepatitis C virus (HCV) infection after liver transplantation (LT). Methods We performed a systematic search for relevant published data on the PubMed, EMBASE, and Cochrane Library databases. Studies that evaluated any regimen in which SOF was used to treat patients with HCV infection after LT and reported the sustained virologic response 12 weeks (SVR12) after therapy were included. Results A total of 12 studies, involving 892 patients, were included in this analysis. The pooled estimate of SVR12 (sustained virologic response 12 weeks) was 88.1%. Subgroup analysis showed that patients who received SOF plus other DAAs had higher SVR12 than those treated with SOF plus ribavirin or peg-IFN. The pooled incidence of any adverse events (AEs) was 73.7%. Conclusions The results of this study showed that the treatment response of SOF-containing regimens in patients with HCV infection after LT was satisfactory. However, more attention needs to be paid to the high rate of AEs associated with such regimens.
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Affiliation(s)
- Hua Fu
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Jiahong Dong
- Hospital and Institute of Hepatobiliary Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, China.,Center of Hepatopancreatobiliary Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Zhide Sun
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Xuejun Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Aijun Yu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Guoli Chen
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
| | - Wei Li
- Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
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16
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Levitsky J, Asrani SK, Klintmalm G, Schiano T, Moss A, Chavin K, Miller C, Guo K, Zhao L, Jennings LW, Brown M, Armstrong B, Abecassis M. Discovery and Validation of a Biomarker Model (PRESERVE) Predictive of Renal Outcomes After Liver Transplantation. Hepatology 2020; 71:1775-1786. [PMID: 31509263 PMCID: PMC7883482 DOI: 10.1002/hep.30939] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 09/05/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). We aimed to develop clinical/protein models to predict future glomerular filtration rate (GFR) deterioration in this population. APPROACH AND RESULTS In independent multicenter discovery (CTOT14) and single-center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma samples at month 3 after LT in recipients with preserved GFR who demonstrated subsequent GFR deterioration versus preservation by year 1 and year 5 in the BUMC cohort. In CTOT14, we also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n = 60). Levels of β-2 microglobulin and CD40 antigen and presence of hepatitis C virus (HCV) infection predicted early (year 1) GFR deterioration (area under the curve [AUC], 0.814). We observed excellent validation of this model (AUC, 0.801) in the BUMC cohort (n = 50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75), and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including β-2 microglobulin and CD40, correlated with GFR changes over the first year. CONCLUSIONS We have validated a clinical/protein model (PRESERVE) that early after LT can predict future renal deterioration versus preservation with high accuracy. This model may help select recipients at higher risk for subsequent CKD for early, proactive renal sparing strategies.
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Affiliation(s)
- Josh Levitsky
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | | | | | | | | | | | | | - Kexin Guo
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Lihui Zhao
- Northwestern University Feinberg School of Medicine, Chicago, IL
| | | | - Merideth Brown
- Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, MD
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17
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Gupta G, Yakubu I, Bhati CS, Zhang Y, Kang L, Patterson JA, Andrews-Joseph A, Alam A, Ferreira-Gonzalez A, Kumar D, Moinuddin IK, Kamal L, King AL, Levy M, Sharma A, Cotterell A, Reichman TW, Khan A, Kimball P, Stiltner R, Baldecchi M, Brigle N, Gehr T, Sterling RK. Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients. Am J Transplant 2020; 20:739-751. [PMID: 31652392 DOI: 10.1111/ajt.15664] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 10/10/2019] [Accepted: 10/13/2019] [Indexed: 01/25/2023]
Abstract
We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.
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Affiliation(s)
- Gaurav Gupta
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.,Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Idris Yakubu
- Virginia Commonwealth University School of Pharmacy, Richmond, Virginia
| | - Chandra S Bhati
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Yiran Zhang
- Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia
| | - Le Kang
- Department of Biostatistics, Virginia Commonwealth University, Richmond, Virginia
| | - Julie A Patterson
- Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia
| | - Ayana Andrews-Joseph
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Anam Alam
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | | | - Dhiren Kumar
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Irfan K Moinuddin
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Layla Kamal
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Anne L King
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.,Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Marlon Levy
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Amit Sharma
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Adrian Cotterell
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Trevor W Reichman
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Aamir Khan
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Pamela Kimball
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Rodney Stiltner
- Virginia Commonwealth University School of Pharmacy, Richmond, Virginia
| | - Mary Baldecchi
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Nathaniel Brigle
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Todd Gehr
- Division of Nephrology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - Richard K Sterling
- Division of Transplantation, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia.,Section of Hepatology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
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18
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Morris KL, Adlam JP, Padanilam M, Patel A, Garcia-Cortes R, Chaudhry SP, Seasor E, Tompkins S, Hoefer C, Zanotti G, Walsh MN, Salerno C, Bochan M, Ravichandran A. Hepatitis C donor viremic cardiac transplantation: A practical approach. Clin Transplant 2019; 34:e13764. [PMID: 31830339 DOI: 10.1111/ctr.13764] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 11/13/2019] [Accepted: 11/25/2019] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Patients with end-stage heart failure eligible for orthotopic heart transplantation (OHT) exceed the number of available donor organs. With highly effective hepatitis C virus (HCV) antiviral therapy now available, HCV+ organs are increasingly utilized. We seek to describe our experience with patients receiving HCV viremic organs as compared to non-HCV transplant recipients. METHODS Our center began utilizing HCV hearts in February 2018. We retrospectively reviewed baseline demographics, laboratory data and outcomes for those undergoing OHT with majority being from a viremic HCV donor. RESULTS Twenty-three of 25 HCV recipients received hearts from NAT+ donors with 22 of 23 seroconverting within 7 days. Fifteen recipients have completed HCV treatment, with the longest duration of follow-up being 13 months. No differences in rates of rejection, hospitalizations or death were seen between non-HCV and HCV transplant patients. DISCUSSION With the advent of available direct-acting antivirals (DAAs), viremic HCV hearts provide an opportunity to increase organ availability. Moreover, treatment for HCV in the setting of immunosuppression is well-tolerated and results in sustained viremic response. CONCLUSION Viremic, discordant HCV OHT can be performed in a safe and effective manner utilizing a systematic, multidisciplinary approach without an effect on short-term outcomes.
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Affiliation(s)
- Kathleen L Morris
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - James P Adlam
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Mathew Padanilam
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Amit Patel
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Rafael Garcia-Cortes
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Sunit-Preet Chaudhry
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Erica Seasor
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Shannon Tompkins
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Caitlin Hoefer
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Giorgio Zanotti
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Mary Norine Walsh
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Christopher Salerno
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Markian Bochan
- Infectious Disease of Indiana, PSC. St. Vincent Hospital, Indianapolis, Indiana
| | - Ashwin Ravichandran
- Department of Cardiology and Advanced Heart Failure and Cardiac Transplantation, PSC. St. Vincent Hospital, Indianapolis, Indiana
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19
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Merli M, Rossotti R, Travi G, Ferla F, Lauterio A, Angelini Zucchetti T, Alcantarini C, Bargiacchi O, De Carlis L, Puoti M. Sustained virological response with 16-week glecaprevir/pibrentasvir after failure to sofosbuvir/velpatasvir in post-transplant severe HCV recurrence in HIV. Transpl Infect Dis 2019; 21:e13165. [PMID: 31487082 DOI: 10.1111/tid.13165] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 07/20/2019] [Accepted: 08/25/2019] [Indexed: 12/01/2022]
Abstract
Direct-acting antivirals (DAAs) demonstrated high efficacy and safety even in the post-liver transplant (LT) setting and in HIV-infected patients, but data are very limited in the early post-LT period with the most recently available DAA. Two HIV/HCV-coinfected LT recipients (both grafts from HIV/HCV-negative donors) experienced early HCV recurrence with severe hepatitis and were treated with sofosbuvir/velpatasvir for 12 weeks. Unfortunately, both patients failed: one (genotype 4d) showed virological breakthrough at week 3 with resistance-associated substitutions (RASs) for both NS5A and NS5B, while the other (genotype 1a) experienced virological relapse without RAS. Both progressed to fibrosing cholestatic hepatitis and were successfully retreated with glecaprevir/pibrentasvir for 16 weeks achieving sustained virological response. The higher prevalence of RAS in experienced genotype 4 patients and the long time to viral suppression observed in subjects with fibrosing cholestatic hepatitis should be taken into account, considering longer treatment duration to increase the chances of achieving sustained virological response.
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Affiliation(s)
- Marco Merli
- Division of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Roberto Rossotti
- Division of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Giovanna Travi
- Division of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Fabio Ferla
- Division of General Surgery & Abdominal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | - Andrea Lauterio
- Division of General Surgery & Abdominal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | | | - Chiara Alcantarini
- Department of Medical Sciences, Unit of Infectious Diseases, Amedeo di Savoia Hospital, University of Torino, Torino, Italy
| | - Olivia Bargiacchi
- Infectious Diseases Section, "Maggiore della Carità" Hospital, Novara, Italy
| | - Luciano De Carlis
- Division of General Surgery & Abdominal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy.,School of Medicine, University of Milano-Bicocca, Milano, Italy
| | - Massimo Puoti
- Division of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
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20
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Bixler D, Annambholta P, Abara WE, Collier MG, Jones J, Mixson-Hayden T, Basavaraju SV, Ramachandran S, Kamili S, Moorman A. Hepatitis B and C virus infections transmitted through organ transplantation investigated by CDC, United States, 2014-2017. Am J Transplant 2019; 19:2570-2582. [PMID: 30861300 PMCID: PMC9112229 DOI: 10.1111/ajt.15352] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 02/14/2019] [Accepted: 03/03/2019] [Indexed: 01/25/2023]
Abstract
We evaluated clinical outcomes among organ recipients with donor-derived hepatitis B virus (HBV) or hepatitis C virus (HCV) infections investigated by CDC from 2014 to 2017 in the United States. We characterized new HBV infections in organ recipients if donors tested negative for total anti-HBc, HBsAg and HBV DNA, and new recipient HCV infections if donors tested negative for anti-HCV and HCV RNA. Donor risk behaviors were abstracted from next-of-kin interviews and medical records. During 2014-2017, seven new recipient HBV infections associated with seven donors were identified; six (86%) recipients survived. At last follow-up, all survivors had functioning grafts and five (83%) had started antiviral therapy. Twenty new recipient HCV infections associated with nine donors were identified; 19 (95%) recipients survived. At last follow-up, 18 (95%) survivors had functioning grafts and 14 (74%) had started antiviral treatment. Combining donor next-of kin interviews and medical records, 11/16 (69%) donors had evidence of injection drug use and all met Public Health Service increased risk donor (IRD) criteria. IRD designation led to early diagnosis of recipient infection, and prompt implementation of therapy, likely reducing the risk of graft failure, liver disease, and death.
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Affiliation(s)
- Danae Bixler
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Pallavi Annambholta
- Office of Blood, Organ and Other Tissue Safety, Division of Health care Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Winston E Abara
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Melissa G. Collier
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Jefferson Jones
- Office of Blood, Organ and Other Tissue Safety, Division of Health care Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Tonya Mixson-Hayden
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Sridhar V Basavaraju
- Office of Blood, Organ and Other Tissue Safety, Division of Health care Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA
| | - Sumathi Ramachandran
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Saleem Kamili
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
| | - Anne Moorman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention (CDC), Atlanta, GA
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21
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Kulkarni HS, Korenblat KM, Kreisel D. Expanding the donor pool for lung transplantation using HCV-positive donors. J Thorac Dis 2019; 11:S1942-S1946. [PMID: 31632793 DOI: 10.21037/jtd.2019.08.27] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Affiliation(s)
- Hrishikesh S Kulkarni
- Divisions of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA
| | - Kevin M Korenblat
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA
| | - Daniel Kreisel
- Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, Saint Louis, MO, USA
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22
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McLean RC, Reese PP, Acker M, Atluri P, Bermudez C, Goldberg LR, Abt PL, Blumberg EA, Van Deerlin VM, Reddy KR, Bloom RD, Hasz R, Suplee L, Sicilia A, Woodards A, Zahid MN, Bar KJ, Porrett P, Levine MH, Hornsby N, Gentile C, Smith J, Goldberg DS. Transplanting hepatitis C virus-infected hearts into uninfected recipients: A single-arm trial. Am J Transplant 2019; 19:2533-2542. [PMID: 30768838 DOI: 10.1111/ajt.15311] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 02/10/2019] [Accepted: 02/11/2019] [Indexed: 02/06/2023]
Abstract
The advent of direct-acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV-infected donors. We conducted a single-arm trial of orthotopic heart transplantation (OHT) from HCV-infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40-65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV-genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt-in for HCV nucleic-acid-test (NAT)+ donor offers to OHT was 39 days (interquartile range [IQR] 17-57). The median donor age was 34 years (IQR 31-37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR-12). The 10th recipient had a positive cross-match, experienced antibody-mediated rejection and multi-organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short-term results suggest that HCV-negative candidates transplanted with HCV-infected hearts have acceptable outcomes.
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Affiliation(s)
- Rhondalyn C McLean
- Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Peter P Reese
- Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.,Department of Biostatistics, Epidemiology and Bioinformatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael Acker
- Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Pavan Atluri
- Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Christian Bermudez
- Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Lee R Goldberg
- Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Peter L Abt
- Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Emily A Blumberg
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Vivianna M Van Deerlin
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - K Rajender Reddy
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Roy D Bloom
- Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Richard Hasz
- Gift of Life Donor Program, Philadelphia, Pennsylvania
| | | | - Anna Sicilia
- Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania
| | - Ashley Woodards
- Department of Biostatistics, Epidemiology and Bioinformatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Muhammad Nauman Zahid
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Katharine J Bar
- Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Paige Porrett
- Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Matthew H Levine
- Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Nicole Hornsby
- Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Caren Gentile
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania
| | - Jennifer Smith
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania
| | - David S Goldberg
- Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.,Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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23
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Verna EC, Schluger A, Brown RS. Opioid epidemic and liver disease. JHEP Rep 2019; 1:240-255. [PMID: 32039374 PMCID: PMC7001546 DOI: 10.1016/j.jhepr.2019.06.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 06/27/2019] [Accepted: 06/29/2019] [Indexed: 12/12/2022] Open
Abstract
Opioid use in the United States and in many parts of the world has reached epidemic proportions. This has led to excess mortality as well as significant changes in the epidemiology of liver disease. Herein, we review the impact of the opioid epidemic on liver disease, focusing on the multifaceted impact this epidemic has had on liver disease and liver transplantation. In particular, the opioid crisis has led to a significant shift in incident hepatitis C virus infection to younger populations and to women, leading to changes in screening recommendations. Less well characterized are the potential direct and indirect hepatotoxic effects of opioids, as well as the changes in the incidence of hepatitis B virus infection and alcohol abuse that are likely rising in this population as well. Finally, the opioid epidemic has led to a significant rise in the proportion of organ donors who died due to overdose. These donors have led to an overall increase in donor numbers, but also to new considerations about the better use of donors with perceived or actual risk of disease transmission, especially hepatitis C. Clearly, additional efforts are needed to combat the opioid epidemic. Moreover, better understanding of the epidemiology and underlying pathophysiology will help to identify and treat liver disease in this high-risk population.
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Affiliation(s)
- Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Aaron Schluger
- Columbia University Vagelos College of Physicians and Surgeons, New York, NY
| | - Robert S. Brown
- Center for Liver Disease and Transplantation, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY
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24
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Xu X, Chen J, Wei Q, Liu ZK, Yang Z, Zhang M, Wang GY, Gao J, Yang ZX, Guo WY, Xing TH, Shao Z, Xie QF, Zheng SS. Clinical practice guidelines on liver transplantation for hepatocellular carcinoma in China (2018 edition). Hepatobiliary Pancreat Dis Int 2019; 18:307-312. [PMID: 31279679 DOI: 10.1016/j.hbpd.2019.06.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 06/11/2019] [Indexed: 02/05/2023]
Affiliation(s)
- Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
| | - Jun Chen
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Zhi-Kun Liu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Ming Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Guo-Ying Wang
- Department of Hepatic Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
| | - Jie Gao
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing 100044, China
| | - Zhao-Xu Yang
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, China
| | - Wen-Yuan Guo
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai 200003, China
| | - Tong-Hai Xing
- General Surgery Center, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China
| | - Zhou Shao
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qin-Fen Xie
- Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310004, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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25
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Bowring MG, Shaffer AA, Massie AB, Cameron A, Desai N, Sulkowski M, Garonzik-Wang J, Segev DL. Center-level trends in utilization of HCV-exposed donors for HCV-uninfected kidney and liver transplant recipients in the United States. Am J Transplant 2019; 19:2329-2341. [PMID: 30861279 PMCID: PMC6658335 DOI: 10.1111/ajt.15355] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 02/15/2019] [Accepted: 03/05/2019] [Indexed: 01/25/2023]
Abstract
Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation.
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Affiliation(s)
- Mary G Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ashton A Shaffer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Allan B Massie
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Andrew Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Niraj Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark Sulkowski
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Jacqueline Garonzik-Wang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
- Scientific Registry of Transplant Recipients, Minneapolis, Minnesota
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26
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Solid organ transplantation of viral hepatitis C positive donor organs into viral hepatitis C negative recipients. Curr Opin Organ Transplant 2019; 23:257-263. [PMID: 29432255 DOI: 10.1097/mot.0000000000000504] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE OF REVIEW Strategies are needed to reduce waitlist mortality and increase transplantation rates. Advances in hepatitis C therapy has allowed the transplant community to look toward utilization of grafts from hepatitis C viremic donors to expand the organ pool. Use of such grafts for hepatitis C-negative patients is being evaluated and debated, and early trial data are emerging. RECENT FINDINGS Both hepatitis C antibody-positive/nucleic acid test-negative and viremic donors are currently underutilized. Outcomes for viral hepatitis C (HCV) viremic transplant recipients are improving in the setting of direct-acting antiviral therapy. Optimization of graft utilization from HCV 'positive' donors and expansion to use of viremic donors for HCV-negative recipients will likely reduce waitlist mortality and result in net overall reduction in healthcare expenditures. SUMMARY Herein, we provide a review of recent advancements relating to hepatitis C in solid organ transplant and outline future directions. A primary future focus will be data collection of outcomes of transplantation of grafts from HCV 'viremic' donors to nonviremic recipients in formal clinical trial protocols.
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27
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Hepatocellular carcinoma in the wait-listed patient with hepatitis C virus. Curr Opin Organ Transplant 2019; 23:237-243. [PMID: 29406448 DOI: 10.1097/mot.0000000000000505] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE OF REVIEW To highlight the current data for treatment of hepatitis C virus (HCV) in patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplant and incorporation of various factors to decide the optimal time to initiate HCV therapy. RECENT FINDINGS Viral eradication on the waiting list has been found to lead to significant clinical improvement in approximately 20% of HCV-positive patients. However, there have been concerns raised for direct-acting antiviral (DAA) therapy in patients listed with HCC. DAA therapy leading to rapid HCV clearance has been reported to be associated with an increased risk of HCC recurrence, especially when DAA therapy is initiated in close proximity to HCC therapy. Additionally, the presence of viable HCC may significantly lower the chances of achieving sustained virologic response. Lastly, sustained virologic response can decrease the organ pool in HCV-positive waitlisted patients. SUMMARY The decision to treat HCV in patients listed for HCC pre vs. postliver transplant will require additional research.
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28
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Woolley AE, Singh SK, Goldberg HJ, Mallidi HR, Givertz MM, Mehra MR, Coppolino A, Kusztos AE, Johnson ME, Chen K, Haddad EA, Fanikos J, Harrington DP, Camp PC, Baden LR. Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients. N Engl J Med 2019; 380:1606-1617. [PMID: 30946553 PMCID: PMC7369135 DOI: 10.1056/nejmoa1812406] [Citation(s) in RCA: 256] [Impact Index Per Article: 42.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. METHODS We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. RESULTS A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. CONCLUSIONS In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).
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Affiliation(s)
- Ann E Woolley
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Steve K Singh
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Hilary J Goldberg
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Hari R Mallidi
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Michael M Givertz
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Mandeep R Mehra
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Antonio Coppolino
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Amanda E Kusztos
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Megan E Johnson
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Kaiwen Chen
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Esther A Haddad
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - John Fanikos
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - David P Harrington
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Phillip C Camp
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
| | - Lindsey R Baden
- From the Divisions of Infectious Diseases (A.E.W., A.E.K., M.E.J., K.C., E.A.H., L.R.B.), Cardiac Surgery (S.K.S., H.R.M.), Thoracic Surgery (S.K.S., H.R.M., A.C., P.C.C.), Pulmonary and Critical Care Medicine (H.J.G.), and Cardiovascular Medicine (M.M.G., M.R.M.), and the Department of Pharmacy (J.F.), Brigham and Women's Hospital, Harvard Medical School (A.E.W., S.K.S., H.J.G., H.R.M., M.M.G., M.R.M., A.C., E.A.H., P.C.C., L.R.B.), Massachusetts College of Pharmacy and Health Sciences (J.F.), the Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute (D.P.H.), and Harvard T.H. Chan School of Public Health (D.P.H.) - all in Boston
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Coilly A, Roche B, Samuel D. Management of HCVInfection After Liver Transplantation. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 4E 2019:753-764. [DOI: 10.1002/9781119211419.ch50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Te H, Doucette K. Viral hepatitis: Guidelines by the American Society of Transplantation Infectious Disease Community of Practice. Clin Transplant 2019; 33:e13514. [DOI: 10.1111/ctr.13514] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 02/12/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Helen Te
- Center for Liver Diseases, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chicago Illinois
| | - Karen Doucette
- Division of Infectious Diseases University of Alberta Edmonton Alberta Canada
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31
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de Godoy AS, Sachetto Fernandes R, Campos Aguiar AC, Vieira Bueno R, de Moraes Roso Mesquita NC, Carvalho Guido RV, Oliva G. Structural and mechanistic insight from antiviral and antiparasitic enzyme drug targets for tropical infectious diseases. Curr Opin Struct Biol 2019; 59:65-72. [PMID: 30954758 DOI: 10.1016/j.sbi.2019.02.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 02/23/2019] [Accepted: 02/28/2019] [Indexed: 12/28/2022]
Abstract
With almost half of the world population living at risk, tropical infectious diseases cause millions of deaths every year in developing countries. Considering the lack of economic prospects for investment in this field, approaches aiming the rational design of compounds, such as structure-based drug discovery (SBDD), fragment screening, target-based drug discovery, and drug repurposing are of special interest. Herein, we focused in the advances on the field of SBDD targeting arboviruses such as dengue, yellow fever, zika and chikungunya enzymes of the RNA replication complex (RC) and enzymes involved in a variety of pathways essential to ensure parasitic survival in the host, for malaria, Chagas e leishmaniasis diseases. We also highlighted successful examples such as promising new inhibitors and molecules already in preclinical/clinical phase tests, major gaps in the field and perspectives for the future of drug design for tropical diseases.
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Affiliation(s)
- Andre Schutzer de Godoy
- Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, São Carlos 13563-120, Brazil
| | - Rafaela Sachetto Fernandes
- Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, São Carlos 13563-120, Brazil
| | - Anna Caroline Campos Aguiar
- Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, São Carlos 13563-120, Brazil
| | - Renata Vieira Bueno
- Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, São Carlos 13563-120, Brazil
| | | | - Rafael Victorio Carvalho Guido
- Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, São Carlos 13563-120, Brazil
| | - Glaucius Oliva
- Institute of Physics of São Carlos, University of São Paulo, Av. Joao Dagnone, 1100 - Jardim Santa Angelina, São Carlos 13563-120, Brazil.
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32
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Diagnostic and therapeutic approach to infectious diseases in solid organ transplant recipients. Intensive Care Med 2019; 45:573-591. [PMID: 30911807 PMCID: PMC7079836 DOI: 10.1007/s00134-019-05597-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2019] [Accepted: 03/06/2019] [Indexed: 12/18/2022]
Abstract
Purpose Prognosis of solid organ transplant (SOT) recipients has improved, mainly because of better prevention of rejection by immunosuppressive therapies. However, SOT recipients are highly susceptible to conventional and opportunistic infections, which represent a major cause of morbidity, graft dysfunction and mortality. Methods Narrative review. Results We cover the current epidemiology and main aspects of infections in SOT recipients including risk factors such as postoperative risks and specific risks for different transplant recipients, key points on anti-infective prophylaxis as well as diagnostic and therapeutic approaches. We provide an up-to-date guide for management of the main syndromes that can be encountered in SOT recipients including acute respiratory failure, sepsis or septic shock, and central nervous system infections as well as bacterial infections with multidrug-resistant strains, invasive fungal diseases, viral infections and less common pathogens that may impact this patient population. Conclusion We provide state-of the art review of available knowledge of critically ill SOT patients with infections.
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33
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Bethea ED, Samur S, Kanwal F, Ayer T, Hur C, Roberts MS, Terrault N, Chung RT, Chhatwal J. Cost Effectiveness of Transplanting HCV-Infected Livers Into Uninfected Recipients With Preemptive Antiviral Therapy. Clin Gastroenterol Hepatol 2019; 17:739-747.e8. [PMID: 30138735 PMCID: PMC6382534 DOI: 10.1016/j.cgh.2018.08.042] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 07/26/2018] [Accepted: 08/13/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Guidelines do not recommend transplanting hepatitis C virus (HCV)-infected livers into HCV-uninfected recipients. Direct-acting antivirals (DAAs) can be used to treat donor-derived HCV infection. However, the added cost of DAA therapy is a barrier. We evaluated the cost effectiveness of transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy. METHODS A previously validated Markov-based mathematical model was adapted to simulate a virtual trial of HCV-negative patients on the liver transplant waitlist. The model compared long-term clinical and economic outcomes in patients willing to accept only HCV-negative livers vs those willing to accept any liver (HCV negative or HCV positive). Recipients of HCV-positive livers received 12 weeks of preemptive DAA therapy. The model incorporated data from the United Network for Organ Sharing and published sources. RESULTS For patients with a model for end-stage liver disease (MELD) score ≥ 22, accepting any liver vs waiting for only HCV-negative livers was cost effective, with incremental cost-effectiveness ratios ranging from $56,100 to $91,700/quality-adjusted life-year. For patients with a MELD score of 28 (the median MELD score of patients undergoing transplantation in the United States), accepting any liver was cost effective at an incremental cost-effectiveness ratio of $62,600/quality-adjusted life year. In patients with low MELD scores, which may not accurately reflect disease severity, accepting any liver was cost effective, irrespective of MELD score. CONCLUSIONS Using a Markov-based mathematical model, we found transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy to be a cost-effective strategy that could improve health outcomes.
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Affiliation(s)
- Emily D Bethea
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Sumeyye Samur
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Turgay Ayer
- Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia
| | - Chin Hur
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Mark S Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Norah Terrault
- University of California San Francisco Medical Center, Gastroenterology and Hepatology Division, San Francisco, California
| | - Raymond T Chung
- Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts
| | - Jagpreet Chhatwal
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, Massachusetts.
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34
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Wadei HM, Pungpapong S, Cortese C, Alexander MP, Keaveny AP, Yang L, Taner CB, Croome KP. Transplantation of HCV-infected organs into uninfected recipients: Advance with caution. Am J Transplant 2019; 19:960-961. [PMID: 30372586 DOI: 10.1111/ajt.15152] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Hani M Wadei
- Department of Transplant, Mayo Clinic, Jacksonville, Florida
| | | | - Cherise Cortese
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida
| | - Mariam P Alexander
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | | | - Liu Yang
- Department of Transplant, Mayo Clinic, Jacksonville, Florida
| | - C Burcin Taner
- Department of Transplant, Mayo Clinic, Jacksonville, Florida
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35
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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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36
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Chan C, Schiano T, Agudelo E, Paul Haydek J, Hoteit M, Laurito MP, Norvell JP, Terrault N, Verna EC, Yang A, Levitsky J. Immune-mediated graft dysfunction in liver transplant recipients with hepatitis C virus treated with direct-acting antiviral therapy. Am J Transplant 2018; 18:2506-2512. [PMID: 30075485 DOI: 10.1111/ajt.15053] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 07/10/2018] [Accepted: 07/29/2018] [Indexed: 01/25/2023]
Abstract
Interferon treatment of hepatitis C virus (HCV) infection after liver transplantation (LT) can result in immune-mediated graft dysfunction (IGD). The occurrence of, risk factors for, and outcomes of IGD with direct-acting antiviral (DAA) therapy have not been reported. We conducted a multicenter study of HCV+LT recipients who did or did not develop DAA-IGD (1 case: 2 controls-33 vs 66). Among all treated between 2014 and 2016, DAA-IGD occurred in 3.4% (33/978). IGD occurred only after treatment completion (76.0 [IQR, 47.0;176]). Among those treated, 48% had plasma cell hepatitis, 36% acute cellular rejection, 6% chronic rejection, and 9% combined findings. Median time to liver enzyme resolution was 77.5 days (IQR, 31.5;126). After diagnosis, hospitalizations, steroid-induced hyperglycemia, and infection occurred in a higher percentage of cases vs controls (33% vs 7.5%, 21% vs 1.5%, 9% vs 0%; all P < .05). Only one IGD patient died and none required retransplant. A multivariate regression analysis found that liver enzyme elevations during and soon after DAA therapy completion correlated with subsequent IGD. In conclusion, while DAA-IGD is uncommon, liver enzyme elevations during or after DAA therapy may be a sign of impending IGD. These indicators should guide clinicians to diagnose and treat IGD early before the more deleterious later clinical presentation.
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Affiliation(s)
- Christine Chan
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Thomas Schiano
- Recanati/ Miller Transplantation Institute and the Division of Liver Diseases, Mount Sinai Medical Center, New York, NY, USA
| | - Eliana Agudelo
- UCSF Medical Center Division of Liver Transplant, San Francisco, CA, USA
| | - John Paul Haydek
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA
| | - Marcela P Laurito
- Department of Medicine, Center for Liver Disease and Transplantation, Columbia University, New York, NY, USA
| | - John P Norvell
- Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Norah Terrault
- UCSF Medical Center Division of Liver Transplant, San Francisco, CA, USA
| | - Elizabeth C Verna
- Department of Medicine, Center for Liver Disease and Transplantation, Columbia University, New York, NY, USA
| | - Amy Yang
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Josh Levitsky
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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37
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Berenguer M, Agarwal K, Burra P, Manns M, Samuel D. The road map toward an hepatitis C virus-free transplant population. Am J Transplant 2018; 18:2409-2416. [PMID: 29935050 DOI: 10.1111/ajt.14976] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 05/14/2018] [Accepted: 06/15/2018] [Indexed: 01/25/2023]
Abstract
Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)-based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN-based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second-generation direct-acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN-based therapy. These agents have the potential to reduce the number of patients developing HCV-related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real-world experience.
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Affiliation(s)
- M Berenguer
- Liver Transplantation & Hepatology Unit, Hospital Universitario La Fe, University of Valencia-CIBEReHD, Valencia, Spain
| | - K Agarwal
- Institute of Liver Studies, King's College Hospital, London, UK
| | - P Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - M Manns
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
| | - D Samuel
- Inserm-Paris Sud Unit 1193, Centre Hepatobiliaire, Hopital Paul Brousse, Villejuif, France
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38
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Shaffer AA, Thomas AG, Bowring MG, Van Pilsum Rasmussen SE, Cash A, Kucirka LM, Alqahtani SA, Gurakar A, Sulkowski MS, Cameron AM, Segev DL, Durand CM. Changes in practice and perception of hepatitis C and liver transplantation: Results of a national survey. Transpl Infect Dis 2018; 20:e12982. [PMID: 30144258 DOI: 10.1111/tid.12982] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 06/14/2018] [Accepted: 08/12/2018] [Indexed: 12/18/2022]
Abstract
With new practice guidelines, it is important to understand how liver transplant (LT) centers have incorporated direct-acting antivirals (DAAs) into the management of hepatitis C virus-infected (HCV+) candidates and recipients. To explore how DAAs have affected LT centers' willingness to treat HCV+ candidates and recipients and to use HCV+ donors, we surveyed high volume US LT centers (11/2014-12/2015) regarding practices for HCV+ candidates, recipients, and donors, before vs after DAAs. We used the Scientific Registry of Transplant Recipients to compare centers' number of LTs, HCV+ recipients, and HCV+ donors in the years before (1/1/2012-12/31/2013) and after (1/1/2016-12/31/2017) survey administration. Of 80 centers contacted, 57 (71.3%) responded, representing 69.0% of the total volume of LTs in 2013. After DAAs, most centers increased treating candidates with low (≤15) model for end-stage liver disease (MELD) (85.2%), intermediate/high (>15) MELD (92.6%), and hepatocellular carcinoma (79.6%). There was consensus to treat low MELD candidates (90.8% "most of the time/always"), but less certainty for intermediate/high MELD candidates (48.2% "sometimes"). Universal post-LT HCV treatment increased (7.4% vs 57.4%). After DAAs, 42.6% were more willing to use HCV+ donors for HCV+ candidates, and 38.9% were willing to consider using HCV+ donors for HCV- candidates. Overall, with DAAs, centers were more willing to treat HCV+ candidates and recipients and to use HCV+ donors; recent recommendations may help to guide treatment decisions for intermediate/high MELD candidates.
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Affiliation(s)
- Ashton A Shaffer
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Alvin G Thomas
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina
| | - Mary Grace Bowring
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Ayla Cash
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Lauren M Kucirka
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Saleh A Alqahtani
- Department of Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ahmet Gurakar
- Department of Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mark S Sulkowski
- Department of Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Christine M Durand
- Department of Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland
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39
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Li AA, Cholankeril G, Cheng XS, Tan JC, Kim D, Toll AE, Nair S, Ahmed A. Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases 2018; 6:E62. [PMID: 29996536 PMCID: PMC6165210 DOI: 10.3390/diseases6030062] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 07/05/2018] [Accepted: 07/09/2018] [Indexed: 12/26/2022] Open
Abstract
In recent years, the opioid epidemic and new hepatitis C virus (HCV) treatments have changed the landscape of organ procurement and allocation. We studied national trends in solid organ transplantation (2000⁻2016), focusing on graft utilization from HCV seropositive deceased donors in the pre-2014 (2000⁻2013) versus current (2014⁻2016) eras with a retrospective analysis of the United Network for Organ Sharing database. During the study period, HCV seropositive donors increased from 181 to 661 donors/year. The rate of HCV seropositive donor transplants doubled from 2014 to 2016. Heart and lung transplantation data were too few to analyze. A higher number of HCV seropositive livers were transplanted into HCV seropositive recipients during the current era: 374 versus 124 liver transplants/year. Utilization rates for liver transplantation reached parity between HCV seropositive and non-HCV donors. While the number of HCV seropositive kidneys transplanted to HCV seropositive recipients increased from 165.4 to 334.7 kidneys/year from the pre-2014 era to the current era, utilization rates for kidneys remained lower in HCV seropositive than in non-HCV donors. In conclusion, relative underutilization of kidneys from HCV seropositive versus non-HCV donors has persisted, in contrast to trends in liver transplantation.
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Affiliation(s)
- Andrew A Li
- Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - George Cholankeril
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Xingxing S Cheng
- Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Jane C Tan
- Division of Nephrology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
| | - Alice E Toll
- United Network for Organ Sharing, Richmond, VA 23219, USA.
| | - Satheesh Nair
- Department of Transplant Surgery, Methodist University Hospital, University of Tennessee Health Science Center, Memphis, TN 38104, USA.
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
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40
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Cortesi PA, Belli LS, Facchetti R, Mazzarelli C, Perricone G, De Nicola S, Cesana G, Duvoux C, Mantovani LG, Strazzabosco M. The optimal timing of hepatitis C therapy in liver transplant-eligible patients: Cost-effectiveness analysis of new opportunities. J Viral Hepat 2018; 25:791-801. [PMID: 29406608 DOI: 10.1111/jvh.12877] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 01/15/2018] [Indexed: 02/06/2023]
Abstract
Different strategies of DAAs treatment are currently possible both pre- and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately investigated; this study aims at assessing their cost-effectiveness. A decision analytical model was created to simulate the progression of HCV-infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12-week course of DAAs prior to transplantation (PRE-LT), (ii) a 4-week course of DAAs starting at the time of transplantation (PERI-LT) and (iii) a 12-week course of DAAs administered at disease recurrence (POST-LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE-LT treatment strategy was dominant for DCC patients with MELD<16 and cost-effective for those with MELD16-20, while POST-LT strategy emerged as cost-effective for DCC patients with MELD>20 and for those with HCC. Sensitivity analyses confirmed PRE-LT as the cost-effective strategy for patients with MELD≤20. In conclusion, PRE-LT treatment is cost-effective for patients with MELD≤20 without HCC, while treatments after LT are cost-effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant-related factors.
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Affiliation(s)
- P A Cortesi
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | - L S Belli
- Department of Hepatology and Gastroenterology, Niguarda Hospital, Milan, Italy.,International Center for Disease Health (ICDH), University of Milan-Bicocca, Monza, Italy
| | - R Facchetti
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | - C Mazzarelli
- Department of Hepatology and Gastroenterology, Niguarda Hospital, Milan, Italy
| | - G Perricone
- Department of Hepatology and Gastroenterology, Niguarda Hospital, Milan, Italy
| | - S De Nicola
- Department of Hepatology and Gastroenterology, Niguarda Hospital, Milan, Italy
| | - G Cesana
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy
| | - C Duvoux
- Department of Hepatology and Liver Transplant Unit, Henri Mondor Hospital, Paris-Est University, Creteil, France
| | - L G Mantovani
- Research Centre on Public Health (CESP), University of Milan-Bicocca, Monza, Italy.,International Center for Disease Health (ICDH), University of Milan-Bicocca, Monza, Italy
| | - M Strazzabosco
- International Center for Disease Health (ICDH), University of Milan-Bicocca, Monza, Italy.,Department of Internal Medicine, Liver Center, Yale University, New Haven, CT, USA
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41
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Moayedi Y, Gulamhusein AF, Ross HJ, Teuteberg JJ, Khush KK. Accepting hepatitis C virus-infected donor hearts for transplantation: Multistep consent, unrealized opportunity, and the Stanford experience. Clin Transplant 2018; 32:e13308. [DOI: 10.1111/ctr.13308] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2018] [Indexed: 12/16/2022]
Affiliation(s)
- Yasbanoo Moayedi
- Division of Cardiovascular Medicine, Heart Transplantation; Stanford University; Stanford CA USA
- Ted Rogers Centre of Excellence in Heart Function; Peter Munk Cardiac Centre; University Health Network; Toronto ON Canada
| | | | - Heather J Ross
- Ted Rogers Centre of Excellence in Heart Function; Peter Munk Cardiac Centre; University Health Network; Toronto ON Canada
| | - Jeffrey J. Teuteberg
- Division of Cardiovascular Medicine, Heart Transplantation; Stanford University; Stanford CA USA
| | - Kiran K. Khush
- Division of Cardiovascular Medicine, Heart Transplantation; Stanford University; Stanford CA USA
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42
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Chhatwal J, Samur S, Bethea ED, Ayer T, Kanwal F, Hur C, Roberts MS, Terrault N, Chung RT. Transplanting hepatitis C virus-positive livers into hepatitis C virus-negative patients with preemptive antiviral treatment: A modeling study. Hepatology 2018; 67:2085-2095. [PMID: 29222916 PMCID: PMC5991982 DOI: 10.1002/hep.29723] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Revised: 10/30/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Under current guidelines, hepatitis C virus (HCV)-positive livers are not transplanted into HCV-negative recipients because of adverse posttransplant outcomes associated with allograft HCV infection. However, HCV can now be cured post-LT (liver transplant) using direct-acting antivirals (DAAs) with >90% success; therefore, HCV-negative patients on the LT waiting list may benefit from accepting HCV-positive organs with preemptive treatment. Our objective was to evaluate whether and in which HCV-negative patients the potential benefit of accepting an HCV-positive (i.e., viremic) organ outweighed the risks associated with HCV allograft infection. We developed a Markov-based mathematical model that simulated a virtual trial of HCV-negative patients on the LT waiting list to compare long-term outcomes in patients: (1) willing to accept any (HCV-negative or HCV-positive) liver versus (2) those willing to accept only HCV-negative livers. Patients receiving HCV-positive livers were treated preemptively with 12 weeks of DAA therapy and had a higher risk of graft failure than those receiving HCV-negative livers. The model incorporated data from published studies and the United Network for Organ Sharing (UNOS). We found that accepting any liver regardless of HCV status versus accepting only HCV-negative livers resulted in an increase in life expectancy when Model for End-Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28 (0.172 additional life-years). The magnitude of clinical benefit was greater in UNOS regions with higher HCV-positive donor organ rates, that is, Regions 1, 2, 3, 10, and 11. Sensitivity analysis demonstrated that model outcomes were robust. CONCLUSION Transplanting HCV-positive livers into HCV-negative patients with preemptive DAA therapy could improve patient survival on the LT waiting list. Our analysis can help inform clinical trials and minimize patient harm. (Hepatology 2018;67:2085-2095).
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Affiliation(s)
- Jagpreet Chhatwal
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Sumeyye Samur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA
| | - Emily D. Bethea
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Turgay Ayer
- Department of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA
| | - Fasiha Kanwal
- Department of Medicine, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX,Houston Veterans Affairs Health Services Research and Development Center of Excellence, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
| | - Chin Hur
- Massachusetts General Hospital Institute for Technology Assessment, Boston, MA,Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
| | - Mark S. Roberts
- Department of Health Policy and Management, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA,University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Norah Terrault
- University of California San Francisco Medical Center, San Francisco, CA
| | - Raymond T. Chung
- Harvard Medical School, Boston, MA,Liver Center and Gastrointestinal Division, Massachusetts General Hospital, Boston, MA
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43
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Selzner N, Berenguer M. Should organs from hepatitis C-positive donors be used in hepatitis C-negative recipients for liver transplantation? Liver Transpl 2018; 24:831-840. [PMID: 29624894 DOI: 10.1002/lt.25072] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 02/10/2018] [Accepted: 03/10/2018] [Indexed: 02/07/2023]
Abstract
Given the scarcity of donated organs and the frequency of death on the waiting list, strategies that could improve the available supply of high-quality liver grafts are much needed. Direct-acting antiviral agent (DAA) regimens have proved to be highly effective to treat hepatitis C virus (HCV), even in the setting of posttransplantation. The question arises as to whether transplant communities should consider the utilization of HCV-positive donors into HCV-negative recipients. This review summarizes risk of transmission, treatment options with success rate, and ethical considerations for usage of HCV-positive donors. Liver Transplantation 24 831-840 2018 AASLD.
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Affiliation(s)
- Nazia Selzner
- Multiorgan Transplant Program, University of Toronto, Toronto, Canada
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, La Fe University Hospital, Universidad de Valencia, Valencia, Spain
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44
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Bari K, Luckett K, Kaiser T, Diwan T, Cuffy M, Schoech MR, Safdar K, Blackard JT, Apewokin S, Paterno F, Sherman KE, Zucker SD, Anwar N, Shah SA. Hepatitis C transmission from seropositive, nonviremic donors to non-hepatitis C liver transplant recipients. Hepatology 2018; 67:1673-1682. [PMID: 29205441 DOI: 10.1002/hep.29704] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/09/2017] [Accepted: 11/28/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Breakthroughs in hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors who are HCV antibody-positive but serum nucleic acid test (NAT)-negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody-negative (n = 25) or NAT-negative (n = 1) transplant recipients who received a liver graft from donors who were HCV antibody-positive but serum NAT-negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV PCR test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died 18 days after transplantation from primary graft nonfunction and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow-up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct-acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated postoperative course and did not receive antiviral therapy. CONCLUSION In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody-positive/NAT-negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose; given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. (Hepatology 2018;67:1673-1682).
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Affiliation(s)
- Khurram Bari
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Keith Luckett
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, OH
| | - Tiffany Kaiser
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Tayyab Diwan
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Madison Cuffy
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Michael R Schoech
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Kamran Safdar
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Jason T Blackard
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Senu Apewokin
- Division of Infectious Diseases, Department of Medicine, University of Cincinnati, Cincinnati, OH
| | - Flavio Paterno
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Stephen D Zucker
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH.,Division of Gastroenterology, Hepatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nadeem Anwar
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH
| | - Shimul A Shah
- Division of Transplant Surgery, Department of Surgery, University of Cincinnati, Cincinnati, OH
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45
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Shafii AE, Harris DD, Baz M. Clearance of Hepatitis C Virus Prior to Lung Transplantation: A Case Report. Transplant Proc 2018; 49:1682-1684. [PMID: 28838464 DOI: 10.1016/j.transproceed.2017.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 06/16/2017] [Indexed: 02/07/2023]
Abstract
Hepatitis C virus (HCV) continues to be considered a relative contraindication to lung transplantation due to concerns of progression of liver disease with the introduction of immunosuppression. Since the recent introduction of effective antiviral therapy for HCV, new approaches in the management of the HCV-positive recipient are being utilized in liver transplantation to clear HCV pre- and post-transplant. Herein, we report use of ledipasvir/sofosbuvir for HCV clearance prior to lung transplantation in a patient with usual interstitial pneumonia. Listing for transplant was delayed until completion of HCV treatment, and he subsequently required extracorporeal membrane oxygenation as a bridge to transplantation due to progressive hypoxia. With antiviral cure rates exceeding 90%, HCV should no longer be considered a relative contraindication to lung transplant, and timing of antiviral treatment should consider the progressive nature of the recipient's lung disease.
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Affiliation(s)
- A E Shafii
- Department of Surgery, Division of Cardiothoracic Surgery, University of Kentucky, Lexington, Kentucky, USA.
| | - D D Harris
- University of Kentucky College of Medicine, Lexington, Kentucky, USA
| | - M Baz
- Department of Surgery, Division of Cardiothoracic Surgery, University of Kentucky, Lexington, Kentucky, USA
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46
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Gonzalez SA, Trotter JF. The rise of the opioid epidemic and hepatitis C-positive organs: A new era in liver transplantation. Hepatology 2018; 67:1600-1608. [PMID: 29023920 DOI: 10.1002/hep.29572] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 09/29/2017] [Indexed: 12/13/2022]
Abstract
The use of hepatitis C virus (HCV)-positive organs in liver transplantation (LT) has increased in the era of direct-acting antiviral therapy. A rising demand for organs, the increased ability to effectively treat HCV infection in the transplant setting, and an unprecedented increase in HCV-positive donors have all contributed to this trend. A recent abrupt rise in opioid use in the United States has resulted in a surge of injection drug use, transmission of HCV, and opioid-related overdose deaths. Geographical areas most affected by the opioid epidemic have experienced a rapid increase in recovery and utilization of HCV-positive donor organs, in which the proportion of deceased donor LTs in the United States from donors who are HCV positive has increased nearly 2-fold within the last 3 years. The prospect of expanding the organ donor pool with HCV-positive donors and achieving acceptable posttransplant outcomes has generated much interest in the areas of liver, kidney, and thoracic transplantation, including the potential for transplanting organs from HCV positive donors into HCV-negative recipients. Developing strategies to ensure appropriate selection of potential recipients of HCV-positive organs, initiating timely antiviral therapy, and defining associated risks will be critical in achieving optimal posttransplant outcomes in this setting. (Hepatology 2018;67:1600-1608).
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Affiliation(s)
- Stevan A Gonzalez
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX and Baylor All Saints Medical Center, Fort Worth, TX
| | - James F Trotter
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX and Baylor All Saints Medical Center, Fort Worth, TX
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47
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Rupp C, Hippchen T, Neuberger M, Sauer P, Pfeiffenberger J, Stremmel W, Gotthardt DN, Mehrabi A, Weiss KH. Successful combination of direct antiviral agents in liver-transplanted patients with recurrent hepatitis C virus. World J Gastroenterol 2018; 24:1353-1360. [PMID: 29599610 PMCID: PMC5871830 DOI: 10.3748/wjg.v24.i12.1353] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/02/2018] [Accepted: 03/18/2018] [Indexed: 02/07/2023] Open
Abstract
AIM To analyze the safety and efficiency of direct-acting antiviral (DAA) regimens in liver-transplanted patients with hepatitis C virus (HCV) reinfection.
METHODS Between January 2014 and December 2016, 39 patients with HCV reinfection after liver transplantation were treated at our tertiary referral center with sofosbuvir (SOF)-based regimens, including various combinations with interferon (IFN), daclatasvir (DAC), simeprivir (SIM) and/or ledipasvir (LDV). Thirteen patients were treated with SOF + IFN ± RBV. Ten patients were treated with SOF + DAC ± RBV. Fiveteen patients were treated with fixed-dose combination of SOF + LDV ± RBV. One patient was treated with SOF + SIM + RBV. Three patients with relapse were retreated with SOF + LDV + RBV. The treatment duration was 12-24 wk in all cases. The decision about the HCV treatment was made by specialists at our transplant center, according to current available or recommended medications.
RESULTS The majority of patients were IFN-experienced (29/39, 74.4%) and had a history of hepatocellular carcinoma (26/39, 66.7%) before liver transplantation. Sustained virological response at 12 wk (SVR12) was achieved in 10/13 (76.9%) of patients treated with SOF + IFN ± RBV. All patients with relapse were treated with fixed-dose combination of SOF + LDV + RBV. Patients treated with SOF + DAC + RBV or SOF + LDV + RBV achieved 100% SVR12. SVR rates after combination treatment with inhibitors of the HCV nonstructural protein (NS)5A and NS5B for 24 wk were significantly higher, as compared to all other therapy regimens (P = 0.007). Liver function was stable or even improved in the majority of patients during treatment. All antiviral therapies were safe and well-tolerated, without need of discontinuation of treatment or dose adjustment of immunosuppression. No serious adverse events or any harm to the liver graft became overt. No patient experienced acute cellular rejection during the study period.
CONCLUSION Our cohort of liver-transplanted patients achieved high rates of SVR12 after a 24-wk course of treatment, especially with combination of NS5A and NS5B inhibitors.
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Affiliation(s)
- Christian Rupp
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
- Interdisciplinary Endoscopy Unit, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Theresa Hippchen
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Manuel Neuberger
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Peter Sauer
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
- Interdisciplinary Endoscopy Unit, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Jan Pfeiffenberger
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Wolfgang Stremmel
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Daniel Nils Gotthardt
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg 69120, Germany
| | - Karl-Heinz Weiss
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg 69120, Germany
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48
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Kwo P, Fried MW, Reddy KR, Soldevila-Pico C, Khemichian S, Darling J, Zamor PJ, Napoli AA, Anduze-Faris B, Brown RS. Daclatasvir and sofosbuvir treatment of decompensated liver disease or post-liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real-world cohort. Hepatol Commun 2018; 2:354-363. [PMID: 29619415 PMCID: PMC5880197 DOI: 10.1002/hep4.1156] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 12/08/2017] [Accepted: 01/11/2018] [Indexed: 12/12/2022] Open
Abstract
We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child‐Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12‐month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks. Sustained virologic response (SVR) at posttreatment week 12 (SVR12) was measured. Assessments adhered to local standards. One patient (prior Child‐Pugh class C who improved to class B) enrolled by exemption was included in the overall data but not the class C cohort efficacy/safety data. Of the 77 treated patients, including 62 liver transplant recipients (genotype 1, n = 43, 69%; genotype 3, n = 16, 26%) and 14 patients with Child‐Pugh class C cirrhosis (genotype 1, n = 4, 29%; genotype 3, n = 10, 71%), 63 (82%) completed treatment. SVR12 rates by modified intention‐to‐treat analysis (excluding nonvirologic failures lost to follow‐up and withdrawal [consent/no reason]) in the overall, liver transplant, and Child‐Pugh class C cohorts were 84% (n = 64/76), 90% (n = 56/62), and 62% (n = 8/13), respectively. Rates increased to 96% (n = 64/67), 97% (n = 56/58), and 89% (n = 8/9), respectively, in patients with available virologic data (including early discontinuations); 22/23 patients with genotype 3 (96%) achieved SVR12. Single cases of virologic nonresponse and relapse (both in liver transplant recipients with genotype 1) and viral breakthrough (Child‐Pugh class C; genotype 3) occurred. Six patients died, 10 had adverse events leading to discontinuation, and 30 experienced serious adverse events. Conclusion: Daclatasvir plus sofosbuvir, with/without ribavirin, provided high SVR12 rates and was generally well tolerated in patients with life‐threatening disease and high unmet needs. (Hepatology Communications 2018;2:354‐363)
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Affiliation(s)
- Paul Kwo
- Division of Gastroenterology and Hepatology Stanford University School of Medicine Palo Alto CA
| | - Michael W Fried
- Department of Medicine University of North Carolina School of Medicine Chapel Hill NC
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology University of Pennsylvania Philadelphia PA
| | | | - Saro Khemichian
- Department of Medicine, Keck School of Medicine University of Southern California Los Angeles CA
| | - Jama Darling
- Department of Medicine University of North Carolina School of Medicine Chapel Hill NC
| | | | | | | | - Robert S Brown
- Department of Medicine Weill Cornell Medicine New York NY
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International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 2018; 101:956-967. [PMID: 28437388 DOI: 10.1097/tp.0000000000001704] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies. J Heart Lung Transplant 2018. [PMID: 29530322 DOI: 10.1016/j.healun.2018.01.1293] [Citation(s) in RCA: 141] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.
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