Intracoronary Intimal Thickness in Transplant Recipients of Hepatitis C-Positive Donor Hearts

Zalawadiya, Sandip; Lindenfeld, JoAnn; Haddad, Elias V.; Shah, Ashish S.; Wigger, M.; Negrotto, Sara; Danter, Matthew; Brinkley, D.; Menachem, Jonathan N.; Punnoose, L.; Sacks, Suzanne Brown; Ooi, Henry; Balsara, Keki R.; Perri, Roman E.; Awad, Joseph; Smith, Sinéad M.; Fowler, R.; O’Dell, Heather; Darragh, C.; Ruzevich-Scholl, S.; Schlendorf, Kelly

doi:10.1016/j.healun.2019.01.703

Cited by 6 publications

(6 citation statements)

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“…These episodes occurred earlier in the NAT‐positive compared with the NAT‐negative recipient group, independent of tacrolimus levels, and the results were maintained at six months of follow‐up. Previous studies have shown that HCV‐positive donor HT has been associated with the development of cardiac allograft vasculopathy 10,11 . Moreover, an analysis of HCV+ donor HT demonstrated that one fourth of HT recipients developed cardiac allograft vasculopathy by 1 year, although no patients required percutaneous or surgical revascularization.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that HCV-positive donor HT has been associated with the development of cardiac allograft vasculopathy. 10,11 Moreover, an analysis of HCV+ donor HT demonstrated that one fourth of HT recipients developed cardiac allograft vasculopathy by 1 year, although no patients required percutaneous or surgical revascularization. Early activation of T lymphocytes after HT in the presence of viremia 12 is a proposed mechanism of early rejection in HCV+ donor HT.…”

Section: F I G U R E 1 Barplots Indicating (A)mentioning

confidence: 99%

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Effect of Hepatitis C donor status on heart transplantation outcomes in the United States

Doulamis

Tzani

Moustakidis³

et al. 2021

Clinical Transplantation

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A potential donor for heart transplantation (HT) is required to meet several selection criteria including negative viral serologies for hepatitis B surface antigen, hepatitis C virus (HCV), and human immunodeficiency virus. A small number of HCV-viremic donors have been transplanted into HCV-negative recipients because of concerns of viral transmission, risk of cirrhosis in the setting of chronic maintenance immunosuppression, poor tolerability of interferon-based therapy and low sustained virologic response (SVR) rates. However, recent evidence on the safety and efficacy of direct-acting antiviral (DAA) therapies for HCV has resulted in the development of alternative strategies to expand the supply of donor organs. Specifically, the use of HCVpositive donors for cardiac transplantation is under investigation as a potential means of expanding the donor pool with excellent SVR and accumulating evidence on safety of this approach. [1][2][3][4][5]

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Section: Discussionmentioning

confidence: 99%

Section: F I G U R E 1 Barplots Indicating (A)mentioning

confidence: 99%

Effect of Hepatitis C donor status on heart transplantation outcomes in the United States

Doulamis

Tzani

Moustakidis³

et al. 2021

Clinical Transplantation

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“…One group has shown that patients who are viremic before initiation of DAA treatment have more marked intimal thickening shown on intravascular ultrasound of the left anterior descending coronary artery. 46…”

Section: Discussionmentioning

confidence: 99%

“…24 As seen in the current review, the success of DAA therapy does not seem to be affected by the timing of initiation. Nevertheless, the long-term consequences of the initial viremic period are unknown, particularly the risk of hepatitis C-induced coronary arteriosclerosis, 46,54 and the possibility of accidental transmission to medical staff should also be considered. In the context of immunosuppression, initial viremia may be extremely high and this could have negative consequences.…”

Section: Discussionmentioning

confidence: 99%

Heart Transplantation From Hepatitis C–Positive Donors in the Era of Direct Acting Antiviral Therapy: A Comprehensive Literature Review

Schnegg

Nicole

Dharan

et al. 2019

Transplantation Direct

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Background.While heart transplantation is a highly effective treatment in patients with advanced heart failure, the number of people waiting for a transplant exceeds the number of available donors. With the advent of direct acting antivirals (DAA) for the eradication of Hepatitis C, the heart transplant donor pool has been expanded to include donors with untreated Hepatitis C. To help with the development of future protocols for Hepatitis C–positive heart transplants, we performed a review of the literature on DAA therapy in the context of heart transplantation.Methods.We searched MEDLINE, EMBASE, OVIDE JOURNAL, and GOOGLE SCHOLAR for papers published between 01.01.2011 and 01.06.2019 using key words “heart transplantation” associated with “hepatitis C.”Results.After removing duplicates, we screened 78 articles and retained 16 for primary analysis and 20 for sustained virologic response 12 weeks after completion of the DAA therapy (SVR-12). The data from 62 patients were extracted from these publications. Fifty-six (90%) patients had donor-derived hepatitis C and 6 (10%) patients were chronically infected with hepatitis C before transplantation. All living transplanted patients achieved SVR-12, defined as hepatitis C virus RNA below the limit of detection 12 weeks after treatment completion. Treatment duration ranged from 4 to 24 weeks. Clinically relevant modification to the dosing of immunosuppressive mediations during DAA therapy was documented in only 1 patient (1.6%). Six (14%) patients experienced rejection during DAA therapy.Conclusions.Despite different timings of initiation of DAA therapy across the included studies, there were no differences in sustained viral clearance. Early commencement of DAA with a potentially shorter treatment duration (<8 wk) is appealing; however, further studies are required before recommending this approach.

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“…The short-term risk of cardiac allograft vasculopathy was evaluated among 14 heart transplant patients serially monitored at Vanderbilt with 6-month (n ¼ 20) and 1-year (n ¼ 16) intravascular ultrasound testing; median maximal intimal thickness was 0.39 mm (IQR, 0.25-0.80 mm) and 0.65 mm (IQR, 0.37-0.98 mm), respectively, with an absolute median increase of 0.15 mm (IQR, -0.03 to 0.42 mm). 27 On the horizon are strategies to inactivate HCV before transplantation to prevent viral transmission altogether. Light-based therapies (LbT) used during normothermic ex vivo lung perfusion (EVLP) is a novel approach to reduce HCV viral load to prevent donor-derived transmission.…”

Section: Long-term Safetymentioning

confidence: 99%

Treading lightly as we step into a new era: Use of hepatitis C virus-infected organs for transplantation

Moayedi

Gulamhusein

Khush

2020

The Journal of Thoracic and Cardiovascular Surgery

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An unprecedented number of heart transplants were performed in the United States during 2016, 1 yet 15% of patients on the waitlist either died or became too sick for transplant. 2 Wait times remain unacceptably high for heart transplant candidates. As a result, there has been growing interest in the development of innovative strategies to mitigate the donor organ shortage. During the past decade, the opioid epidemic in the United States has led to a dramatic increase in the number of organ donors who died as a result of drug intoxication. 3 Closely associated with this rise, hepatitis C virus (HCV) infection increased by 400% among 18-to 29-year olds and 325% in 30-to 39-year olds during the same time period. 4 Historically, many of these HCVviremic (herein referred to as HCV-infected) donor organs would be discarded due to anticipated poor recipient shortand long-term survival after transplantation. However, mechanistic insights into the replication of HCV have enabled the development of highly effective and well tolerated direct acting antivirals (DAA) for HCV treatment. 5 This article provides an overview of the management of HCV-infected donor organs, highlighting important considerations in the setting of thoracic transplantation. We discuss the current status of using HCV-infected organs for transplantation, the remaining long-term uncertainties of this approach, and novel strategies for using HCVinfected organs. Currently, a minority of HCV-infected organs are accepted for thoracic transplantation. Based on a United Network Organ Sharing registry analysis, only 64 of 1078 HCV-infected donor hearts were accepted for transplantation from 2014 to 2017. 6 These donors had otherwise favorable characteristics: they were young with a median age of 32 years (interquartile range [IQR], 27-37 years) and had significantly fewer comorbidities such as diabetes and hypertension when compared with the general donor population. 6,7 Based on this registry analysis, more than 800 donor hearts were discarded due to HCV infection, which may represent a valuable missed opportunity for critically ill candidates on the waitlist. Many transplant centers, those particularly in United Network Organ Sharing regions 3, 4, 7, 8, 9, and 10 have been very cautious about accepting HCV-infected organs (Figure 1). The treatment of chronic HCV infection has evolved from the highly toxic and poorly tolerated interferon-and ribavirin-containing regimens to the new landscape of DAA agents. 8 There are currently 4 classes of DAAs, each targeting a unique nonstructural viral protein: NS3/NS4A protease inhibitors, inhibitors of the NS5A complex, and inhibitors of the NS5B polymerase that are subdivided into nucleos(t)ide inhibitors and nonnucleos(t) ide inhibitors and differ in individual potency and barriers to resistance. 8,9 In 2014, the Food and Drug Association approved the first interferon and ribavirin-free regimen consisting of a once-daily combination pill (sofosbuvir/ ledipasvir). 8 Early studies in the transplant setting established t...

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Intracoronary Intimal Thickness in Transplant Recipients of Hepatitis C-Positive Donor Hearts

Cited by 6 publications

References 0 publications

Effect of Hepatitis C donor status on heart transplantation outcomes in the United States

Effect of Hepatitis C donor status on heart transplantation outcomes in the United States

Heart Transplantation From Hepatitis C–Positive Donors in the Era of Direct Acting Antiviral Therapy: A Comprehensive Literature Review

Treading lightly as we step into a new era: Use of hepatitis C virus-infected organs for transplantation

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