n engl j med 373;4nejm.orgjuly 23, 2015PERSPECTI VE303Expansion of Retail Clinicsmovement toward value-based care wont erase all the obstacles facing retail health clinics, but the train has definitely left the station.Disclosure forms provided by the author are available with the full text of this article at NEJM.org.Mr. Iglehart is a national correspondent for the Journal.1.BachrachD,FrohlichJ,GarcimondeA, NevittK.Buildingacultureofhealth:the value proposition of retail clinics. Princeton, NJ: Manatt Health Solutions, 2015.2.TaverniseS.Doctoring,withoutthedoc-tor. New York Times, May 25, 2015:D1.3.Chang JE, Brundage SC, Burke GC, Chok-shiDA.Convenientcare:retailclinicsand urgent care centers in New York State. New York:UnitedHospitalFund,2015(https://www.uhfnyc.org/publications/881033).4.Pollack CE, Armstrong K. The geographic accessibility of retail clinics for underserved populations. Arch Intern Med 2009;169:945-9.5.HwangJ,MehrotraA.Whyretailclinics failedtotransformhealthcare.Harvard Business Review. December 25, 2013 (https://hbr.org/2013/12/why-retail-clinics-failed-to -transform-health-care).DOI: 10.1056/NEJMp1506864Copyright 2015 Massachusetts Medical Society.Transplanting Hepatitis CPositive KidneysPeter P. Reese, M.D., M.S.C.E., Peter L. Abt, M.D., Emily A. Blumberg, M.D., and David S. Goldberg, M.D., M.S.C.E.Thescarcityofkidneysfor transplantation and high mor-tality among patients on the wait-inglisthaveledsomepatientsto accept kidney transplants that car-ryelevatedrisksoftransmitting infectionsorcancer.Incertain cases, such as the transmission of cytomegalovirus,physicianscan anticipatetheseeventsandinsti-tutepreventivemeasures.But transplantteamsoftendiscard kidneysfromdonorswithhepa-titisCvirus(HCV)infection becauseofthemanycomplica-tionsandhistoricalbarriersto successful treatment of HCV. We believe,however,thatnewanti-viraltherapieswithcurerates exceeding95%1shouldprompt transplantleaderstoviewHCV-positive organs as a valuable op-portunityfortransplantcandi-dates with or without preexisting HCV infection.Of course, intentional HCV in-fectionthroughtransplantation willrequirerigorousprograms thataddressthecomplexityof HCVtreatmentoptions,bolster informedconsent,andovercome costconcerns.Buttheresulting expansion of the donor pool could save hundreds of lives each year.Kidney transplantation extends life and saves money as compared withlong-termdialysis,2butits availabletoanever-smallerper-centageofpatients.Inmanyre-gionsoftheUnitedStates,aver-agewaitingtimesforakidney transplantexceed5years,espe-ciallyforpatientswithblood typeOorB,forwhomtheresa largeimbalancebetweenorgan supply and demand. Average mor-talityamongwait-listedpatients is 4% per year, and rates are much higher among diabetic and elderly transplant candidates. The kidney-transplantwaitinglistexceeds 100,000candidates,andthou-sands of other patients receiving dialysiswhomightbenefitfrom transplantation are never even re-ferred.Thesegrimrealitieshave promptedaggressiveeffortsto procurekidneysthatwouldpre-viously have been considered un-acceptable,includingkidneys from donors older than 70 years ofage,kidneysthathavesus-tainedacuteinjury,andkidneys with diverse infections.Usingnationalregistrydata, we identified 3273 HCV-antibody-positivedeceaseddonorsfrom 2005through2014(thepositive predictivevalueoftheantibody test for chronic HCV infection is 80to90%)forwhomorgando-nationwasauthorized.Ofthese 6546kidneys,only2402(37%) were transplanted; 91% of the re-cipientshaddocumentedHCV infection. The other kidneys were discarded, although most were of goodquality(accordingtothe KidneyDonorProfileIndex,a widelyusedtransplantmetric). Thesediscardedkidneyscould havebenefitedmorethan4000 patientsduringthatperiodand provided more than 12,000 years ofgraftlifeby5yearsafter transplantation (see table). In ad-dition,anunknownnumberof kidneyswereneverprocuredbe-cause of legitimate concerns that notransplantcenterwouldac-cept them.ThisreluctancetouseHCV-positiveorgansreflectspastex-perienceswithpost-transplanta-tionHCVcomplications,both hepatic (e.g., cirrhosis) and extra-hepatic(e.g.,glomerulonephritis that can injure the transplant). It also stems from the problem that interferon, the historical mainstay ofHCVtreatment,causestrans-plantrejection.IntheUnited States, the overwhelming major-ity of HCV infections are caused by genotype 1, which has histori-callybeendifficulttotreat.For these reasons, HCV-positive kid-neys are rarely transplanted into The New England Journal of Medicine Downloaded from nejm.org on August 3, 2015. For personal use only. No other uses without permission. Copyright 2015 Massachusetts Medical Society. All rights reserved. PERSPECTI VEn engl j med 373;4nejm.orgjuly 23, 2015304uninfectedrecipients,andthe limited data available suggest that uninfected patients who do receive them have high mortality.3Now, however, highly effective novel therapeutics may transform the way that transplant physicians andtheirpatientsthinkabout HCV-positivedonatedkidneys. Thesetherapiesdonotrequire interferon, and they cure HCV in more than 95% of patients. Accep-tance of transplantation of HCV-positivekidneyswouldresultin shorter waiting times. According to one study, the median waiting timewas469daysforpatients whoacceptedHCV-positivekid-neys, versus 856 days for patients who received HCV-negative organs; anunknownnumberofaddi-tionalpatientsdiedbeforethey could receive a transplant.4Nevertheless, using HCV-posi-tivetransplantsinuninfected patientsraisesmanyconcerns. Which patients should be encour-agedtoacceptthesekidneys? HCVtreatmentiscostly:more than $80,000 for a 3-month regi-men.Canpaymentforpost-transplantation HCV treatment in uninfected patients be guaranteed? Even if patients receive such treat-ment, what are the residual risks ofviralcomplications?Whatis the risk of transmission to inti-matepersonalcontacts?Itis difficulttoestimatethesizeof these risks because newly infect-ed transplant recipients will simul-taneously receive immunosuppres-sive drugs.Theseconcernsmaybeal-layedbyrecentexperiencewith treatmentofHCVinliver-trans-plantrecipients.WhenanHCV-positive patient receives an HCV-negativeliver,theallograftis immediately exposed to HCV from the recipient and becomes infect-ed. Clinical studies have demon-stratedthatthesepatientshave highHCVcurerates,suggesting that immunosuppression does not impede HCV eradication and that interactionsbetweenHCVand transplant drugs can be success-fully managed.5 Nevertheless, giv-entheuncertaintiesaboutrisk, is informed consent possible?Theethicsofknowinglyin-fecting transplant recipients with HCV depends on the rigor of in-formedconsentandthewilling-nessofmedicalprofessionalsto givegreaterweighttopatients autonomy than to minimizing the possibility of iatrogenic harm. In ourview,transplantphysicians should offer HCV-positive organs touninfectedpatientswhohave ahighriskofhealthdeteriora-tioniftheycontinuedialysis (e.g.,elderlypatientsorthose withseriouscoexistingcondi-tions such as cardiovascular dis-ease),disadvantageousblood types,orotherconditionsthat probablymeanmanyyearsof waitingbeforeanappropriate HCV-negativekidneycanbeob-tained.Forsuchvulnerablepa-tients, HCV-positive donated kid-neyscouldprovideasingular opportunitytoundergotrans-plantation.Giventhesurvival benefit of kidney transplantation inpatientswithchronicHCV, thereisreasontobelievethat providingHCV-positivekidneys andHCVtherapytoHCV-nega-tiverecipientswillleadtobetter outcomes than dialysis.Informed-consentprocesses should include explicit communi-cationoftheuncertaintyabout theHCVcureratewithpost-transplantation treatment and the potential risks of viral complica-tions.Severecomplicationsmay include acute hepatitis or fibros-Transplanting Hepatitis CPositive KidneysDisposition of 6546 Kidneys from 3273 Deceased Donors with Hepatitis C Antibody between 2005 and 2014.*Disposition of Kidney PairsNo. ofDonors (%)No. ofKidneysDiscardedMedian Kidney Donor ProfileIndex (IQR)Estimated Additional Graft-Years Obtainable by Transplanting Both Kidneys1-Yr Survival 3-Yr Survival 5-Yr SurvivalBoth kidneys discarded 1718 (52.5) 3436 0.85 (0.670.96) 3000 7637 10,3011 kidney transplanted, 1 discarded 708 (21.6) 708 0.71 (0.540.87) 636 1675 2,361Both kidneys transplanted 847 (25.9) 0 0.60 (0.430.77) * A hepatitis C virus (HCV)positive donor was defined by a positive antibody test for hepatitis C; data are national registry data from the Organ Procurement and Transplantation Network. Discarded kidneys are those for which donation authorization was obtained but thatwere never procured, were procured for research purposes rather than transplantation, or were procured with the intent of transplantation but then discarded. Of the 4144 discarded kidneys, 2698 (65.1%) were procured with the intent of transplantation. The Kidney Donor Profile Index, indicating the quality of a donated kidney, ranges from 0 (highest quality) to 1 (lowest quality); the donors HCV antibody status is considered in the score, which is based on data from an earlier era of HCV treatment. Estimates of additional graft-years obtain-able by transplanting both kidneys were based on the median-quality kidney in each category. IQR denotes interquartile range.The New England Journal of Medicine Downloaded from nejm.org on August 3, 2015. For personal use only. No other uses without permission. Copyright 2015 Massachusetts Medical Society. All rights reserved. n engl j med 373;4nejm.orgjuly 23, 2015PERSPECTI VE305ingcholestaticHCV,although those problems rarely develop in recipients of transplanted organs otherthanlivers.Consentpro-cesses should start when the pa-tient registers on the waiting list andbereinforcedatlatermeet-ings.Atwo-stageconsentpro-cess already exists for transplan-tationoforgansdesignatedas high-risk by the U.S. Public Health Service;thisapproachwillonly require modifications specific to theuncertaintiesregardingHCV aftertransplantation.Ininitial demonstration projects, transplant teamsshouldseekoversight from institutional review boards. Subsequently,multicentertrials could collect comprehensive data on HCV cure rates, viral compli-cations, and time to transplanta-tionforpatientswhoaccept these organs.Althoughtransplantteams may feel challenged by the com-plexity of these discussions, there areprecedentsforthem.Many physicianshaveexperiencewith riskcommunicationrelatedto transplantationoforgansfrom donorswithpastinfectionsor cancers. In the 1990s, similar con-cernswereraisedaboutorgans that tested positive for hepatitis B coreantibodywhicharenow commonlytransplanted,thanks toreassuringresults.Giventhe complexity of decision making in the realm of HCV-positive kidney transplantationforHCV-negative recipients,webelievethatre-searchshouldfocusonrelevant patient-centeredoutcomes.Stud-iescouldexaminecommunica-tionbyphysiciansandthepro-portionofpatientswhoregret accepting an HCV-positive kidney.Costconcernscouldderail suchaninitiative.ButtheCen-tersforMedicareandMedicare Services(CMS)andotherpayers couldcreatemechanismsfor hospitals to obtain pretransplan-tationagreementsforpost-trans-plantation HCV treatment. Copay-mentsfortreatmentshouldbe modest, opening this pathway to transplantationtopatientswith limited means. Though the costs of transplanting HCV-positive kid-neysintouninfectedrecipients wouldbehigh,theymightwell be substantially offset by savings fromreduceddialysistimefor recipientswhowouldotherwise waitlongerforakidney.2Given the increased probability of com-plications,CMSandinsurers couldalsoauthorizehigherpay-mentstructuresforcentersthat used higher-risk kidneys such as HCV-positive organs.Novelantiviraltherapieswill gradually transform how we think about HCV. HCV-positive kidneys could become a valuable resource forpatientswhowouldother-wise have little chance of kidney transplantation. Taking advantage of this resource will require pro-viders, regulatory authorities, and payerstoreconsidernotionsof reasonable risk.Dr. Reese is chair of the Ethics Committee oftheUnitedNetworkforOrganSharing (UNOS); Dr. Abt is co-chair of the Ameri-can Society of Transplant Surgeons (ASTS) Ethics Committee. The views expressed in this article are those of the authors and do not necessarily represent those of UNOS or the ASTS.Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.FromtheRenal-ElectrolyteandHyperten-sionDivision(P.P.R.),theDepartmentsof BiostatisticsandEpidemiology(P.P.R., D.S.G.)andSurgery(P.L.A.),andtheDivi-sionsofInfectiousDiseases(E.A.B.)and Gastroenterology(D.S.G.),Perelman SchoolofMedicine,UniversityofPennsyl-vania, Philadelphia.1.Afdhal N, Zeuzem S, Kwo P, et al. Ledipas-vir and sofosbuvir for untreated HCV geno-type 1 infection. N Engl J Med 2014;370:1889-98.2.Schnitzler MA, Lentine KL, Burroughs TE. The cost effectiveness of deceased organ do-nation. Transplantation 2005;80:1636-7.3.Abbott KC, Bucci JR, Matsumoto CS, et al. Hepatitis C and renal transplantation in the eraofmodernimmunosuppression.JAm Soc Nephrol 2003;14:2908-18.4.KucirkaLM,SingerAL,RosRL,Mont-gomeryRA,DagherNN,SegevDL.Under-utilization of hepatitis C-positive kidneys for hepatitisC-positiverecipients.AmJTrans-plant 2010;10:1238-46.5.ReddyKR,EversonGT,FlammSL,etal. Ledipasvir/sofosbuvirwithribavirinforthe treatmentofHCVinpatientswithpost-transplant recurrence: preliminary results of aprospective,multicenterstudy.Hepatol-ogy 2014;60:200A. abstract.DOI: 10.1056/NEJMp1505074Copyright 2015 Massachusetts Medical Society.Transplanting Hepatitis CPositive KidneysThe New England Journal of Medicine Downloaded from nejm.org on August 3, 2015. For personal use only. No other uses without permission. Copyright 2015 Massachusetts Medical Society. All rights reserved.