Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients

Woolley, Ann E.; Singh, Steve K.; Goldberg, Hilary J.; Mallidi, Hari R.; Givertz, Michael M.; Mehra, Mandeep R.; Coppolino, Antonio; Kusztos, Amanda E.; Johnson, Megan E.; Chen, Kaiwen; Haddad, E.; Fanikos, John; Harrington, David P.; Camp, Phillip C.; Baden, Lindsey R.

doi:10.1056/nejmoa1812406

Cited by 289 publications

(290 citation statements)

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“…Of our 6 viremic patients, there was evidence of significant posttransplant leukopenia in 5 (83%). Recent studies suggest a seroconversion rate of ~ 50% in recipients of HCV NAT + organs . It is worth noting that none of our 6 patients seroconverted despite persistent viremia.…”

Section: Discussionmentioning

confidence: 55%

“…Thus, we theorized that at least in some cases the inoculum of donor virus might be small enough to enable spontaneous clearance or clearance with a short prophylactic course of DAA. It is important to note that we developed and initiated our study prior to detailed published results for the THINKER and EXPANDER‐1 studies and well before the study in heart and lung transplant recipients . We also took into account the pharmacokinetics of sofosbuvir in patients with end‐stage renal disease.…”

Section: Discussionmentioning

confidence: 99%

“…Another small real‐world study on 4 patients reported 100% SVR12 with initiation of G/P immediately pretransplant and then continued for 8 weeks posttransplant as per the approved label . It is of interest that the heart/lung transplant trial that reported on a 4‐week regimen used no T cell depletion induction immunosuppression in their recipients . Containment of HCV infection requires a coordinated CD4 T cell, CD8 T cell, and NK cell response to the virus .…”

Section: Discussionmentioning

confidence: 99%

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Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

Gupta

Yakubu

Bhati

et al. 2020

American Journal of Transplantation

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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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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

Gupta

Yakubu

Bhati

et al. 2020

American Journal of Transplantation

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“…First, the introduction of new DAA treatments has considerably reshaped the landscape of HCV treatment, prompting a discussion about the optimal timing of HCV treatment and trade‐offs between pre‐LT and post‐LT treatment, given the potential for liver recovery . At the same time, the notion of donor‐derived HCV transmission in transplantation has also received a great deal of attention due to the possibility of significantly increasing the pool of transplantable organs . These findings highlight the importance of constantly updating the guidelines in the context of the rapidly changing landscape of HCV in LT.…”

Section: Discussionmentioning

confidence: 99%

Temporal Changes and Regional Variation in Acceptance of Hepatitis C Virus–Viremic Livers

Mazur

Goldberg

2019

Liver Transpl

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The high efficacy of current hepatitis C virus (HCV) therapy and increased numbers of HCV‐infected deceased donors have changed the paradigm of HCV in liver transplantation (LT). Modeling studies have been performed to evaluate the optimal timing of HCV treatment (before versus after LT) in HCV‐infected patients and to assess the cost‐effectiveness of transplanting HCV‐infected livers into HCV− patients. However, these models rely on historical data and have not quantified the temporal changes in the median Model for End‐Stage Liver Disease (MELD) score at transplant of recipients of an HCV‐infected liver across geographic areas. We performed a retrospective cohort study of Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data of nonstatus 1 deceased donor LT recipients from January 1, 2016, to December 31, 2018, and we calculated the difference in allocation MELD score in recipients of HCV nucleic acid test (NAT)− versus NAT+ livers by year and UNOS region. We used Pearson correlation coefficients to assess the relationship between MELD score difference in recipients of HCV NAT+ versus HCV NAT− livers and the proportion of non‐HCV recipients of HCV NAT+ livers. Nationally, the allocation MELD score difference at LT in recipients of HCV NAT+ versus NAT− livers did not change (4‐point difference). This stability was seen in regions 3, 5, and 10. In regions 1, 7, 8, 9, and 11, the MELD score difference decreased, which is a diminishing advantage. However, in regions 2 and 4, it increased, which is a rising advantage. In 2018, recipients of HCV NAT+ livers had a lower MELD score in 9/11 regions, and the MELD score advantage of accepting HCV NAT+ livers had a moderate inverse correlation with the regional use in non‐HCV patients (r = −0.53). These data should be used to inform clinicians of the pre‐ and post‐LT trade‐offs of HCV treatment.

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“…Wooley et al conducted a single‐center, open‐label pilot trial of patients receiving organ transplantation from HCV‐infected donors of various genotypes (n = 44 with 36 lung and 8 heart transplants) who received 4 weeks of sofosbuvir and velpatasvir immediately after transplantation. The authors found that, on follow‐up, all 35 patients (100%) were alive with excellent graft function and undetectable viral load 6 months after transplantation . Further data are needed regarding outcomes associated with liver transplantation, as well as optimal treatment duration and timing.…”

Section: Hepatitis C: From Chronic Malady To Robust Curementioning

confidence: 99%

Chronic Viral Hepatitis: Current Management and Future Directions

Reau

2020

Hepatol Commun

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The past decade has seen transformation in the strategies for identifying and managing viral hepatitis, most dramatically the transformation of hepatitis C virus from a mostly chronic affliction to a curable disease that is accessible to wide populations through direct‐acting antiviral therapies. More recently, shifting of hepatitis C virus burden to younger patients driven by intravenous drug use has shaped screening recommendations. Future work focusing on effective screening, linkage to care, treatment initiation, and post‐cure management will allow countries to work toward meeting goals of eliminating viral hepatitis as a major public health threat. Concurrently, hepatitis B virus has also seen advances in management using oral nucleos(t)ide therapies with high‐resistance barriers. However, virologic cure remains elusive in the setting of viral genetic persistence within the hepatocyte nucleus, even with suppressive antiviral therapy. Future directions include a refined definition of “cure,” new biomarkers, and development of therapies targeting multiple pathways in the viral pathogenic and replication pathway. Progress is additionally being made on the management of hepatitis D infection. This review summarizes the recent evolution in disease characteristics, associated affected population, and changes in our understanding of management for these infections. We also discuss future directions in the management of viral hepatitis, including discussion on issues related to management before and after antiviral therapy. Conclusion: We summarize recent advances in the identification and management of viral hepatitis, which hold the potential to markedly reduce disease burden and therefore associated liver‐related complications. However further work is needed to adequately identify and manage these diseases.

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Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients

Abstract: Dr. Mehra reports receiving fees for serving as a clinical trial leader from Abbott, Medtronic, and Janssen, and advisory board fees from NuPulseCV, Portola, Bayer, and FineHeart. No other potential conflict of interest relevant to this article was reported.

Cited by 289 publications

References 20 publications

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients

Temporal Changes and Regional Variation in Acceptance of Hepatitis C Virus–Viremic Livers

Chronic Viral Hepatitis: Current Management and Future Directions

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