Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
DAA | direct-acting antiviral |
HCV | hepatitis C virus |
ESRD | end-stage renal disease |
OPTN/UNOS | Organ Procurement Transplant Network/United Network for Organ Sharing |
SVR | sustained virological response |
KDPI | Kidney Donor Profile Index |
MELD | Model for End-Stage Liver Disease |
NAT | Nucleic Acid Testing |
References
- Kwo, P.Y.; Mantry, P.S.; Coakley, E.; Te, H.S.; Vargas, H.E.; Brown, R., Jr.; Gordon, F.; Levitsky, J.; Terrault, N.A.; Burton, J.R., Jr.; et al. An interferon-free antiviral regimen for HCV after liver transplantation. N. Engl. J. Med. 2014, 371, 2375–2382. [Google Scholar] [CrossRef] [PubMed]
- Curry, M.P.; Forns, X.; Chung, R.T.; Terrault, N.A.; Brown, R., Jr.; Fenkel, J.M.; Gordon, F.; O’Leary, J.; Kuo, A.; Schiano, T.; et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: An open-label study. Gastroenterology 2015, 148, 100–107. [Google Scholar] [CrossRef] [PubMed]
- Levitsky, J.; Verna, E.C.; O’Leary, J.G.; Bzowej, N.H.; Moonka, D.K.; Hyland, R.H.; Arterburn, S.; Dvory-Sobol, H.; Brainard, D.M.; McHutchison, J.G.; et al. Perioperative ledipasvir–sofosbuvir for HCV in liver-transplant recipients. N. Engl. J. Med. 2016, 375, 2106–2108. [Google Scholar] [CrossRef] [PubMed]
- Colombo, M.; Aghemo, A.; Liu, H.; Zhang, J.; Dvory-Sobol, H.; Hyland, R.; Yun, C.; Massetto, B.; Brainard, D.M.; McHutchison, J.G.; et al. Treatment with ledipasvir–sofosbuvir for 12 or 24 weeks in kidney transplant recipients with chronic hepatitis C virus genotype 1 or 4 infection. Ann. Intern. Med. 2017, 166, 109. [Google Scholar] [CrossRef] [PubMed]
- Reese, P.P.; Harhay, M.N.; Abt, P.L.; Levine, M.H.; Halpern, S.D. New solutions to reduce discard of kidneys donated for transplantation. J. Am. Soc. Nephrol. 2016, 27, 973–980. [Google Scholar] [CrossRef] [PubMed]
- Reese, P.P.; Abt, P.L.; Blumberg, E.A.; Goldberg, D.S. Transplanting hepatitis C-positive kidneys. N. Engl. J. Med. 2015, 373, 303–305. [Google Scholar] [CrossRef] [PubMed]
- Kucirka, L.M.; Singer, A.L.; Ros, R.L.; Montgomery, R.A.; Dagher, N.N.; Segev, D.L. Underutilization of hepatitis C-positive kidneys for hepatitis c-positive recipients. Am. J. Transplant. 2010, 10, 1238–1246. [Google Scholar] [CrossRef] [PubMed]
- Kucirka, L.M.; Peters, T.G.; Segev, D.L. Impact of donor hepatitis C virus infection status on death and need for liver transplant in hepatitis C virus-positive kidney transplant recipients. Am. J. Kidney Dis. 2012, 60, 112–120. [Google Scholar] [CrossRef] [PubMed]
- Scalea, J.; Barth, R.; Munivenkatappa, R.; Cooper, M.; Whitlow, V.; Philosophe, B.; LaMattina, J. Shorter waitlist time for HCV+ renal allografts improves long-term graft survival without associated progression of clinical liver disease. Transplantation 2014, 98, 187. [Google Scholar] [CrossRef]
- Mandal, A.K.; Kraus, E.S.; Samaniego, M.; Rai, R.; Humphreys, S.L.; Ratner, L.E.; Maley, W.R.; Burdick, J.F. Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors. Clin. Transplant. 2000, 14, 391–396. [Google Scholar] [CrossRef] [PubMed]
- Woodside, K.J.; Ishihara, K.; Theisen, J.E.; Early, M.G.; Covert, L.G.; Hunter, G.C.; Gugliuzza, K.K.; Daller, J.A. Use of kidneys from hepatitis C seropositive donors shortens waitlist time but does not alter one-yr outcome. Clin. Transplant. 2003, 17, 433–437. [Google Scholar] [CrossRef] [PubMed]
- Sawinski, D.; Patel, N.; Appolo, B.; Bloom, R. Use of HCV+ donors does not affect HCV clearance with directly acting antiviral therapy but shortens the wait time to kidney transplantation. Transplantation 2017, 101, 968–973. [Google Scholar] [CrossRef] [PubMed]
- Durand, C.; Brown, D.; Wesson, R.; Bhair, N.; Naqvi, F.; Ostrander, D.; Bowring, M.; Massie, A.; Rasmussen, S.; Sugarman, J.; et al. EXPANDER-1: Exploring renal transplants using hepatitis-C infected donors for HCV-negative recipients. Am. J. Transplant. 2017, 17, 207. [Google Scholar]
- Shah, A.P.; Cameron, A.; Singh, P.; Frank, A.M.; Fenkel, J.M. Successful treatment of donor-derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens. Transplant. Infect. Dis. 2017, 19, e12660. [Google Scholar] [CrossRef] [PubMed]
- Goldberg, D.S.; Abt, P.L.; Blumberg, E.A.; Van Deerlin, V.M.; Levine, M.; Reddy, K.R.; Bloom, R.D.; Nazarian, S.M.; Sawinski, D.; Porrett, P.; et al. Trial of transplantation of HCV-infected kidneys into uninfected recipients. N. Engl. J. Med. 2017, 376, 2394–2395. [Google Scholar] [CrossRef] [PubMed]
- Sezer, S.; Ozdemir, F.N.; Akcay, A.; Arat, Z.; Boyacioglu, S.; Haberal, M. Renal transplantation offers a better survival in HCV-infected ESRD patients. Clin. Transplant. 2004, 18, 619–623. [Google Scholar] [CrossRef] [PubMed]
- Ingsathit, A.; Kamanamool, N.; Thakkinstian, A.; Sumethkul, V. Survival advantage of kidney transplantation over dialysis in patients with hepatitis C: A systematic review and meta-analysis. Transplantation 2013, 95, 943–948. [Google Scholar] [CrossRef] [PubMed]
- Maluf, D.G.; Fisher, R.A.; King, A.L.; Gibney, E.M.; Mas, V.R.; Cotterell, A.H.; Shiffman, M.L.; Sterling, R.K.; Behnke, M.; Posner, M.P. Hepatitis C virus infection and kidney transplantation: Predictors of patient and graft survival. Transplantation 2007, 83, 853–857. [Google Scholar] [CrossRef] [PubMed]
- Goldberg, D.S.; Blumberg, E.; McCauley, M.; Abt, P.; Levine, M. Improving organ utilization to help overcome the tragedies of the opioid epidemic. Am. J. Transplant. 2016, 16, 2836–2841. [Google Scholar] [CrossRef] [PubMed]
- CDC. Provisional Counts of Drug Overdose Deaths; CDC: Atlanta, GA, USA, 2017.
- Chute, D.F.; Sise, M.E. Effect of the opioid crisis on the donor pool for kidney transplantation: An analysis of national kidney deceased donor trends from 2010–2016. Am. J. Nephrol. 2018, 47, 84–93. [Google Scholar] [CrossRef] [PubMed]
- Lin, M.V.; Chung, R. Recent FDA approval of sofosbuvir and simeprevir. Implications for current HCV treatment. Clin. Liver Dis. 2014, 3, 65–68. [Google Scholar] [CrossRef] [Green Version]
- Rao, P.S.; Schaubel, D.E.; Guidinger, M.K.; Andreoni, K.A.; Wolfe, R.A.; Merion, R.M.; Port, F.K.; Sung, R.S. A comprehensive risk quantification score for deceased donor kidneys: The kidney donor risk index. Transplantation 2009, 88, 231–236. [Google Scholar] [CrossRef] [PubMed]
- Feng, S.; Goodrich, N.P.; Bragg-Gresham, J.L.; Dykstra, D.M.; Punch, J.D.; DebRoy, M.A.; Greenstein, S.M.; Merion, R.M. Characteristics associated with liver graft failure: The concept of a donor risk index. Am. J. Transplant. 2006, 6, 783–790. [Google Scholar] [CrossRef] [PubMed]
- Humar, A.; Morris, M.; Blumberg, E.; Freeman, R.; Preiksaitis, J.; Kiberd, B.; Schweitzer, E.; Ganz, S.; Caliendo, A.; Orlowski, J.P.; et al. Nucleic acid testing (NAT) of organ donors: Is the “best” test the right test? A consensus conference report. Am. J. Transplant. 2010, 10, 889–899. [Google Scholar] [CrossRef] [PubMed]
- Kling, C.E.; Perkins, J.D.; Landis, C.S.; Limaye, A.P.; Sibulesky, L. Utilization of organs from donors according to hepatitis C antibody and nucleic acid testing status: Time for change. Am. J. Transplant. 2017, 17, 2863–2868. [Google Scholar] [CrossRef] [PubMed]
- Sibulesky, L.; Kling, C.E.; Blosser, C.; Johnson, C.K.; Limaye, A.P.; Bakthavatsalam, R.; Leca, N.; Perkins, J.D. Are we underestimating the quality of aviremic hepatitis C-positive kidneys? Time to reconsider. Am. J. Transplant. 2018. [Google Scholar] [CrossRef] [PubMed]
- Cholankeril, G.; Li, A.A.; March, K.L.; Yoo, E.R.; Kim, D.; Snyder, H.; Gonzalez, S.A.; Younossi, Z.M.; Ahmed, A. Improved outcomes in HCV patients following liver transplantation during the era of direct-acting antiviral agents. Clin. Gastroenterol. Hepatol. 2018, 16, 452–453. [Google Scholar] [CrossRef] [PubMed]
- Cholankeril, G.; Li, A.A.; Cholankeril, R.; Toll, A.E.; Glenn, J.S.; Ahmed, A. Impact of drug overdose deaths on solid organ transplantation in the United States. J. Gen. Intern. Med. 2018. [Google Scholar] [CrossRef] [PubMed]
HCV Seropositive Donors | HCV Seronegative Donors | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Donors | Organs Procured | Organs Transplanted | Donors | Organs Procured | Organs Transplanted | |||||
Year | N | N | Per Donor | N | Per Donor | N | N | Per Donor | N | Per Donor |
2000 | 181 | 460 | 2.54 | 316 | 1.75 | 5804 | 21,039 | 3.62 | 18,710 | 3.22 |
2001 | 197 | 473 | 2.4 | 301 | 1.53 | 5883 | 21,451 | 3.65 | 19,054 | 3.24 |
2002 | 213 | 519 | 2.44 | 343 | 1.61 | 5977 | 21,895 | 3.66 | 19,763 | 3.31 |
2003 | 252 | 562 | 2.23 | 369 | 1.46 | 6205 | 22,337 | 3.6 | 20,039 | 3.23 |
2004 | 301 | 690 | 2.29 | 404 | 1.34 | 6849 | 24,453 | 3.57 | 21,562 | 3.15 |
2005 | 285 | 679 | 2.38 | 379 | 1.33 | 7308 | 26,152 | 3.58 | 22,980 | 3.14 |
2006 | 322 | 726 | 2.25 | 383 | 1.19 | 7695 | 27,512 | 3.58 | 24,121 | 3.13 |
2007 | 352 | 780 | 2.22 | 433 | 1.23 | 7733 | 27,525 | 3.56 | 23,841 | 3.08 |
2008 | 335 | 741 | 2.21 | 411 | 1.23 | 7654 | 27,135 | 3.55 | 23,568 | 3.08 |
2009 | 348 | 773 | 2.22 | 448 | 1.29 | 7674 | 27,523 | 3.59 | 23,841 | 3.11 |
2010 | 331 | 783 | 2.37 | 439 | 1.33 | 7612 | 27,681 | 3.64 | 24,226 | 3.18 |
2011 | 320 | 751 | 2.35 | 458 | 1.43 | 7806 | 28,095 | 3.6 | 24,574 | 3.15 |
2012 | 335 | 765 | 2.28 | 453 | 1.35 | 7808 | 27,837 | 3.57 | 24,172 | 3.1 |
2013 | 361 | 843 | 2.34 | 482 | 1.34 | 7907 | 28,560 | 3.61 | 25,031 | 3.17 |
2014 | 436 | 976 | 2.24 | 601 | 1.38 | 8160 | 29,182 | 3.58 | 25,509 | 3.13 |
2015 | 535 | 1202 | 2.25 | 832 | 1.56 | 8544 | 30,715 | 3.59 | 26,708 | 3.13 |
2016 | 661 | 1506 | 2.28 | 1061 | 1.61 | 9309 | 33,854 | 3.64 | 29,436 | 3.16 |
HCV Seropositive Donor HCV Seropositive Recipient | HCV Seropositive Donor HCV Seronegative Recipient | |||
---|---|---|---|---|
Pre-2014 Era | Current Era | Pre-2014 Era | Current Era | |
Heart | 0.67 | 0.55 | 3.01 | 2.23 |
Lung | 0.18 | 0.00 | 0.54 | 0.40 |
Liver | 25.27 | 59.62 | 4.09 | 3.99 |
Kidney | 17.50 | 28.23 | 4.67 | 2.89 |
Pre-2014 Era (N = 2274) | Current Era (N = 1004) | p Value | |
---|---|---|---|
Donor age (years) | 44.0 (34.0–49.0) | 32.0 (26.0–39.0) | <0.001 |
Donor gender | 0.860 | ||
Female | 800 (35.2%) | 350 (34.9%) | |
Male | 1474 (64.8%) | 654 (65.1%) | |
Donor ethnicity | <0.001 | ||
White | 1681 (73.9%) | 847 (84.4%) | |
Black | 319 (14.0%) | 54 (5.4%) | |
Hispanic | 247 (10.9%) | 91 (9.1%) | |
Donor ABO | 0.503 | ||
A | 701 (30.8%) | 327 (32.6%) | |
Ab | 15 (0.7%) | 10 (1.0%) | |
B | 281 (12.4%) | 115 (11.5%) | |
O | 1277 (56.2%) | 552 (55.0%) | |
Donor PHS increased risk | 666 (39.2%) | 781 (77.8%) | <0.001 |
Donor clinical infection | 1022 (44.9%) | 724 (72.2%) | <0.001 |
Donor mechanism of death | <0.001 | ||
Drug intoxication | 228 (10.0%) | 433 (43.1%) | |
Asphyxiation | 60 (2.6%) | 73 (7.3%) | |
Cardiovascular | 177 (7.8%) | 107 (10.7%) | |
Gunshot wound | 261 (11.5%) | 83 (8.3%) | |
Blunt injury | 546 (24.0%) | 171 (17.0%) | |
ICH/stroke | 905 (39.8%) | 108 (10.8%) | |
Death from natural causes | 35 (1.5%) | 11 (1.1%) | |
None of the above | 39 (1.7%) | 10 (1.0%) | |
KDPI (ref. Population = 2016) | 68.0 (50.0–84.0) | 49.0 (37.0–63.0) | <0.001 |
Cold ischemic time (hours) | 19.0 (13.4–24.4) | 16.6 (11.0–23.0) | <0.001 |
Recipient age | 55.0 (49.0–59.0) | 60.0 (56.0–64.0) | <0.001 |
Recipient dialysis prior | 2077 (91.3%) | 861 (85.8%) | <0.001 |
Pre-2014 Era (N = 1724) | Current Era (N = 1122) | p Value | |
---|---|---|---|
Donor age (years) | 44.0 (32.0–51.0) | 35.0 (28.0–47.0) | <0.001 |
Donor gender | 0.586 | ||
Female | 657 (38.1%) | 439 (39.1%) | |
Male | 1067 (61.9%) | 683 (60.9%) | |
Donor ethnicity | <0.001 | ||
White | 1200 (69.6%) | 910 (81.1%) | |
Black | 344 (20.0%) | 120 (10.7%) | |
Hispanic | 156 (9.0%) | 74 (6.6%) | |
Donor ABO | 0.240 | ||
A | 598 (34.7%) | 422 (37.6%) | |
Ab | 29 (1.7%) | 23 (2.0%) | |
B | 179 (10.4%) | 99 (8.8%) | |
O | 918 (53.2%) | 578 (51.5%) | |
Donor PHS increased risk | 659 (46.5%) | 878 (78.3%) | <0.001 |
Donor clinical infection | 789 (45.8%) | 812 (72.4%) | <0.001 |
Donor mechanism of death | <0.001 | ||
Drug intoxication | 241 (14.0%) | 484 (43.1%) | |
Asphyxiation | 42 (2.4%) | 42 (3.7%) | |
Cardiovascular | 167 (9.7%) | 159 (14.2%) | |
Gunshot wound | 167 (9.7%) | 55 (4.9%) | |
Blunt injury | 337 (19.5%) | 139 (12.4%) | |
ICH/stroke | 702 (40.7%) | 204 (18.2%) | |
Death from natural causes | 26 (1.5%) | 13 (1.2%) | |
None of the above | 28 (1.6%) | 19 (1.7%) | |
Liver donor risk index | 1.4 (1.1–1.6) | 1.2 (1.1–1.5) | <0.001 |
Cold ischemic time (hours) | 6.6 (5.0–8.6) | 6.0 (4.7–7.4) | <0.001 |
Recipient age (years) | 55.0 (51.0–59.0) | 60.0 (55.0–63.0) | <0.001 |
Recipient dialysis prior | 112 (6.5%) | 139 (12.4%) | <0.001 |
MELD lab score at transplant | 16.0 (12.0–22.0) | 18.0 (12.0–23.0) | 0.0511 |
Recipient HCC diagnosis (ever) | 38 (57.6%) | 456 (51.6%) | 0.352 |
Ascites at transplant | <0.001 | ||
Absent | 339 (21.0%) | 341 (30.4%) | |
Slight | 852 (52.7%) | 516 (46.0%) | |
Moderate | 417 (25.8%) | 265 (23.6%) | |
Encephalopathy at transplant | <0.001 | ||
None | 536 (33.1%) | 501 (44.7%) | |
1–2 | 934 (57.8%) | 549 (48.9%) | |
3–4 | 138 (8.5%) | 72 (6.4%) | |
N/A | 9 (0.6%) | 0 (0.0%) |
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Share and Cite
Li, A.A.; Cholankeril, G.; Cheng, X.S.; Tan, J.C.; Kim, D.; Toll, A.E.; 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, 62. https://doi.org/10.3390/diseases6030062
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(3):62. https://doi.org/10.3390/diseases6030062
Chicago/Turabian StyleLi, Andrew A., George Cholankeril, Xingxing S. Cheng, Jane C. Tan, Donghee Kim, Alice E. Toll, Satheesh Nair, and Aijaz Ahmed. 2018. "Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era" Diseases 6, no. 3: 62. https://doi.org/10.3390/diseases6030062
APA StyleLi, A. A., Cholankeril, G., Cheng, X. S., Tan, J. C., Kim, D., Toll, A. E., Nair, S., & Ahmed, A. (2018). Underutilization of Hepatitis C Virus Seropositive Donor Kidneys in the United States in the Current Opioid Epidemic and Direct-Acting Antiviral Era. Diseases, 6(3), 62. https://doi.org/10.3390/diseases6030062