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...
