Roger is a 48-year-old man with end-stage heart failure due to amyloid cardiomyopathy. He is tolerating maximal medical therapy including an angiotensin converting enzyme inhibitor, cardio-selective beta-blocker, aldosterone antagonist, and cardiac resynchronization therapy. He also has an implantable defibrillator. Despite maximal medical treatment, he has Class IV New York Heart Association Heart Failure symptoms with dyspnea at rest. Recently, Roger had an episode of ventricular tachycardia, requiring hospitalization. Roger is aware of the challenges associated with cardiac transplantation but given his symptoms and prognosis, cardiac transplantation is recommended as therapy.
A suitable cardiac transplant has become available, but the donor has active hepatitis C virus (HCV) infection with a positive HCV nucleic acid amplification test. Roger is negative for HCV infection and concerned about accepting the organ. However, the advent of direct-acting antiviral agents to treat HCV raises the possibility of transplanting HCV-infected organs to uninfected recipients without transmitting HCV infection.
In an open-label pilot study recently published in NEJM, Wooley et al. investigated the safety and efficacy of a preemptive course of direct-acting antiviral therapy in HCV uninfected adults after transplantation of thoracic organs from thoracic organs from donors with evidence of active HCV infection. Organ recipients were treated with sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for four weeks, with the first dose administered a few hours after transplant. The results showed that in patients without HCV infection who received a heart or lung transplant from donors with HCV viremia, prompt antiviral treatment for 4 weeks prevented the establishment of chronic HCV infection.
The following Journal Watch summary explains the study and findings:
Hearts and Lungs from Hepatitis C Virus–Infected Donors Were Safely Transplanted into HCV-Negative Recipients
Daniel Kaul, MD reviewing Woolley AE et al. N Engl J Med 2019 Apr 3
Preemptive short courses of direct-acting antivirals prevented clinically significant donor-transmitted hepatitis C.
The opioid epidemic has produced a growing number of potentially transplantable organs from donors who had hepatitis C virus (HCV) infection. At the same time, the use of direct-acting antivirals (DAAs) has decreased the pool of HCV-infected recipients. To avoid waste of these organs, the liver and kidney transplant community offered HCV-infected organs to HCV-negative recipients, curing and preventing infection with posttransplant DAAs (NEJM JW Infect Dis May 2018 and Ann Intern Med 2018; 168:533). Now, investigators report a single-center study of outcomes in heart and lung recipients.
Forty-four HCV seronegative recipients received organs (36 lung; 8 heart) from HCV-infected donors. Most (42/44) developed detectable posttransplant HCV viremia, and all received 4 weeks of the pangenotypic combination DAA sofosbuvir-velpatasvir, initiated immediately after transplant. Viremia cleared within 2 weeks in all recipients. The trial was stopped early when the efficacy stopping boundary was met. All 35 patients who survived to 6 months posttransplant had undetectable HCV and graft survival. No drug-related serious adverse events occurred, but a trend toward increased incidence of low-grade acute cellular rejection was noted in lung, but not heart, recipients compared with contemporaneous recipients of organs from HCV-negative donors.
Comment: This study provides further reassurance that DAAs successfully cure donor-transmitted HCV infection. In this study, a pangenotypic DAA was given immediately after transplant, with rapid clearance of infection. Rather than the typical 12-week treatment course, a short, 4-week course was selected, which would considerably decrease cost. Patient education and informed consent are critical aspects of intentional donor transmission of infection. Interestingly, this study demonstrated widespread acceptance among recipients, as only eight patients declined to participate.
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Angela is a 2018-2019 NEJM editorial fellow. She is an endocrine fellow who trained at Flinders Medical Centre and the Royal Adelaide Hospital. Angela recieved her medical degree from the University of Adelaide, and masters of public health from the University of Sydney. Her clinical and research interests are in the areas of glucocorticoid and cardiovascular endocrinology and diabetes medicine.