Transplanting Lungs From Donors Who Are Hepatitis C-Positive: Effective Antiviral Therapies Expand the Donor Pool
August 8, 2022
In medicine, advances in one field can translate into improvements in other fields, even if distantly related. Second generation direct-acting antiviral (DAA) medications that effectively treat hepatitis C are a major advancement in infectious diseases and have also propelled solid organ transplantation forward. In the Division of Lung Transplant and Lung Failure, part of the UPMC Department of Cardiothoracic Surgery, Pablo Sanchez, MD, and his team have adopted protocols utilizing DAAs to expand the donor pool for lung transplant. These protocols have rapidly become standard of care to allow lung transplants from hepatitis C virus (HCV)-positive donors to HCV-naïve recipients and increase the number of lung transplants possible.
Lung transplantation is the only definitive treatment for end-stage lung disease, but there is an overwhelming disproportion between the high demand for the life-saving procedure and the low supply of organs available for transplant. In 2019, 316 people in the United States died while on the lung transplant waiting list, a waitlist mortality rate of 14.6%.1 Some improvements have increased the number of available organs. Technology-driven strategies, such as ex vivo lung perfusion (EVLP), allow transplant surgeons to better evaluate donated lungs that were initially considered marginal to determine if the lungs may, in fact, be suitable to transplant; protocols are being tested to recondition lungs of marginal quality using EVLP. The number of donor lungs available has also increased through expanded donor eligibility criteria, including the use of lungs from donation after circulatory death (DCD). Additionally, over the last five years, the number of possible lung transplants has increased due to the number of individuals who have tragically died of a drug overdose. These individuals are typically younger and have fewer comorbidities than potential donors who die from other causes, such as trauma or cardiovascular accident (CVA). However, injection drug use is the most common mode of hepatitis C virus (HCV) transmission in the United States, and it is estimated that the prevalence of HCV in injection drug users is approximately 50%.2
The development of effective DAAs with limited adverse profiles to treat approximately 2 million people in the United States living with HCV was a major advancement that decreased the morbidity and mortality associated with chronic HCV. Prior to the development of these second-generation DAAs, organs from HCV-positive (HCV+) donors were rarely used in HCV-naïve recipients. The ethical considerations of potentially trading one life-threatening disease for another, the potential for clinical complications, and documented poorer survival outcomes were considerable barriers. Transmission to the recipient is almost guaranteed when the donor has an active HCV infection. The current generation of DAAs has expanded efficacy against multiple HCV genotypes and has improved safety profiles and more limited drug interactions than previous therapeutics. These second generation DAAs made substantially increasing the donor pool by allowing the use of HCV-positive donors possible. Many organs discarded in the past because of the HCV status of the donor would have been otherwise suitable for transplantation. Using data from the Scientific Registry of Transplant Recipients to inform a donor prediction model, Mooney and colleagues estimated that the ability to use HCV+ donors for lung transplant would increase the number of lung transplants performed in the United States by at least 55 lung transplants per year.3 DAAs have been shown to effectively treat HCV infection that arises after transplant of kidney, liver, heart, and lung.4,5
Clinical trials and retrospective series have established that transplant of lungs from an HCV+ donor into an HCV-naïve recipient with treatment with DAAs either prophylactically or after detection of HCV transmission yields transplant outcomes that are at least as good as transplant of lungs from an HCV-negative (HCV-) donor. Woolley and colleagues performed 36 lung and eight heart transplants from March 2017 through July 2018 using organs from HCV+ donors and then prophylactically treated recipients with DAAs for four weeks. HCV was undetectable after two weeks in most patients and was undetectable in all patients six months after transplant. Low-grade acute cellular rejection occurred in 13 recipients of HCV+ organs, which was significantly more than in than recipients of HCV- organs, but all patients responded to treatment of rejection.6,7 Cypel and colleagues compared outcomes in recipients of lungs from 22 donors who were HCV+ with outcomes of recipients of lungs from 187 HCV- donors over an approximately one-year study period. All the lungs from HCV+ donors were placed on EVLP prior to transplant. Waitlist time was significantly shorter for the recipients of lungs from an HCV+ donor. Almost all recipients (90%) of lungs from HCV+ donors developed HCV viremia within one week of transplantation, and those patients then underwent 12-week treatment with DAAs. Two patients had relapse of HCV viremia and required further treatment to eventually achieve a sustained virologic response at 12 weeks. Survival six months posttransplant (95%) was similar to survival of recipients of lungs from HCV- donors (94%). Other outcome variables assessed, including primary graft dysfunction three days posttransplant, length of hospital and intensive care unit stay, and incidence of acute rejection, were also not significantly affected by the use of an HCV+ donor and DAA therapy posttransplant.8 Similarly, a UNOS database study comparing outcomes of lung transplants in 189 patients who received donated lungs from HCV+ donors with almost 10,000 recipients who underwent lung transplant using lungs from an HCV donor found no differences in survival up to one year posttransplant or in any of the other outcome indicators evaluated, which included graft failure, airway dehiscence, acute rejection, and reintubation. The HCV+ donors were younger, and their lungs had better gas exchange function than the HCV donors.9 Lung transplantation using HCV+ donors quickly became standard of care at UPMC due to strong evidence of safety and the potential to provide a life-saving procedure to more patients by expanding the donor pool. In our experience in the high-volume center in the UPMC Department of Cardiothoracic Surgery, the quality of the lungs from HCV+ donors is very often exceptionally good.
As we established this program, we collaborated with infectious disease specialists at UPMC to define our care protocols. When the lung donor has a positive antibody testing result for HCV but a negative nucleic acid testing result, transmission rates are very low. We monitor the recipients of these lungs and treat with DAAs if they seroconvert to an HCV+ state. When the lung donor is HCV+ by both antibody and nucleic acid testing, we treat the recipient with DAAs prophylactically starting 60 to 90 days after transplant. None of the 20 patients we have transplanted with lungs from an HCV+ donor as of March 2022 have developed chronic HCV infection. When a potential lung transplant recipient is listed for a transplant, they are given the option of considering lungs from an HCV+ donor along with being asked to consider lungs from an extended criteria donor. It is unusual for a potential lung transplant recipient to turn down an offer due to the HCV+ status of the donor. In last five to 10 years, the idea of receiving donated organs from an HCV+ individual has become more accepted by potential transplant recipients. Although there is still room for improvement, it has been satisfying to see this progression. When formally surveyed, only 12.5% of recipients of a lung transplant from an HCV+ donor reported second thoughts about accepting the organ. In fact, most (83%–87%) never felt any anxiety about HCV posttransplant and did not think HCV had impacted them.10
Beginning with the approval of clinical trials for thoracic transplants using organs from HCV+ donors in 2017, UPMC has been committed to developing this care protocol to increase the number of patients who can be treated annually with a life-saving procedure for end-stage disease. The multidisciplinary care that our lung transplant candidates and recipients rely on is well-established and a priority at UPMC. Above all, the goal of the entire UPMC Lung Transplantation Program is to provide as many patients as possible with healthy lungs via expertly performed procedures with excellent care before and after the transplant surgery.
References
1. Valapour M, Lehr CJ, Skeans MA, Smith JM, Miller E, Goff R, et al. OPTN/SRTR 2019 Annual Data Report: Lung. Am J Transplant. 2021;21 Suppl 2:441-520.
2. Hepatitis C Questions and Answers for Health Professionals: U.S. Department of Health & Human Services; 2020 [updated August 7, 2020]. Available from: https:// www.cdc.gov/hepatitis/hcv/hcvfaq.htm.
3. Mooney JJ, Purington N, Mohabir P, Dhillon GS. Estimated impact of hepatitis C-positive lung donor utilization on US donor lung supply. Am J Transplant. 2020;20(1):289-97.
4. Raasikh T, Jamali T, Flores A, Cotton RT, Ramanathan V, Tan HP, et al. Systematic review: hepatitis C viraemic allografts to hepatitis C-negative recipients in solid organ transplantation. Aliment Pharmacol Ther. 2021;54(5):571-82.
5. Kappus MR, Wolfe CR, Muir AJ. Direct-Acting Antivirals and Organ Transplantation: Is There Anything We Can’t Do? J Infect Dis. 2020;222(Suppl 9):S794-S801.
6. Woolley AE, Singh SK, Goldberg HJ, Mallidi HR, Givertz MM, Mehra MR, et al. Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients. N Engl J Med. 2019;380(17):1606-17.
7. Chan EG, Chan PG, Sanchez PG. Expanding the pool: the use of hepatitis C RNA positive organs in lung transplantation. J Thorac Dis. 2019;11(Suppl 15):S1888-S90.
8. Cypel M, Feld JJ, Galasso M, Pinto Ribeiro RV, Marks N, Kuczynski M, et al. Prevention of viral transmission during lung transplantation with hepatitis C-viraemic donors: an open-label, single-centre, pilot trial. Lancet Respir Med. 2020;8(2):192-201.
9. Li SS, Osho A, Moonsamy P, Wolfe S, Villavicencio MA, Langer N, et al. Outcomes of Lung Transplantation From Hepatitis C Viremic Donors. Ann Thorac Surg. 2021.
10. Humar SS, Pinzon N, Cypel M, Abbey S. Lung transplant recipient attitudes and beliefs on accepting an organ that is positive for hepatitis C virus. Transpl Infect Dis. 2021;23(4):e13684.
