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

Abstract

Background: Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.

Methods: We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.

Results: A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.

Conclusions: In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).

Figure 1.. Trial Design and Patient Populations.

Panel A shows the trial design for treatment and monitoring tests after transplantation, and Panel B shows eligibility, screening, randomization, and transplantation in the trial patients. HBsAg denotes hepatitis B virus surface antigen, and NAT nucleic acid amplification test.

Figure 2.. Results of Patient Follow-up after Transplantation.

The black X indicates that Patient 1 died at week 32. The green bars represent patients who had not completed 16 weeks of follow-up by July 31, 2018.

Figure 3.. HCV RNA Levels.

Panel A shows the hepatitis C viral loads in the donors and recipients. Donor viral loads were measured at the time of organ procurement, and recipient viral loads were measured immediately after transplantation. There were 41 donors and 44 recipients; both the heart and lungs were procured from 3 donors, whereas a single organ, either the heart or lung, was procured from the other 38 donors. Panel B shows the decreases in the hepatitis C viral load in patients after transplantation. The viral load cleared in all recipients by approximately 2 weeks. The dashed line indicates the lower limit of quantification.