Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C

Abstract

IMPORTANCE For patients awaiting heart transplant, hepatitis C-positive donors offer an opportunity to expand the donor pool, shorten wait times, and decrease wait-list mortality. While early reported outcomes among few heart transplant recipients have been promising, knowledge of 1-year outcomes in larger cohorts of patients is critical to shared decision-making with patients about this option.OBJECTIVE To better define the association of hepatitis C-positive donors with heart transplant volumes, wait-list duration, the transmission and cure of donor-derived hepatitis C, and morbidity and mortality at 1 year. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, single-center observational study of 80 adult (age 18 years or older) patients who underwent heart transplant using hearts from hepatitis C-positive donors between September 2016 and April 2019 at a large academic medical center. Among donors, who were considered hepatitis C-positive if results from hepatitis C antibody and/or nucleic acid testing were positive, 70 had viremia and 10 were seropositive but did not have viremia. Follow-up was available through May 15, 2019. Comparisons were drawn with patients who underwent transplant with hearts from hepatitis C-negative donors during the same period.EXPOSURES In addition to standard posttransplant management, transplant recipients who developed donor-derived hepatitis C infection were treated with direct-acting antivirals. MAIN OUTCOMES AND MEASURESThe main outcomes included wait-list duration and 1-year survival in all patients, and for those who developed donor-derived hepatitis C, the response to direct-acting antiviral treatment. RESULTSOf 80 patients, 57 (71.3%) were men, 55 (68.7%) were white, and 17 (26.3%) were black; the median age at transplant was 54.5 years (interquartile range, 46-62 years). Following consent to accept hearts from hepatitis C-exposed donors, the median days to heart transplant was 4 (interquartile range, 1-18). No recipients of donors with negative nucleic acid testing results (10 [12.5%]) developed donor-derived hepatitis C. Of 70 patients who were recipients of donors with positive nucleic acid testing results, 67 (95.7%) developed donor-derived hepatitis C over a median follow-up of 301 days (interquartile range, 142-617). Treatment with direct-acting antivirals was well tolerated and yielded sustained virologic responses in all treated patients. Within the cohort with infection, 1-year patient survival was 90.4%, which was not significantly different compared with the cohort without infection or with patients who received transplants from hepatitis C-negative donors during the same period. CONCLUSIONS AND RELEVANCEIn the era of direct-acting antivirals, hepatitis C-positive donors are a viable option to expand the donor pool, potentially reducing wait-list duration and mortality. In heart transplant recipients with donor-derived hepatitis C, infection is well-tolerated and curable, and 1-year survival is equivalent to that in recipients of hepatitis C-negative donors.

Evaluation of Case Volumes of a Heart Transplant Program and Short-term Outcomes After Changes in the United Network for Organ Sharing Donor Heart Allocation System

“… 1 , 2 For example, donor sequence number dictates how likely it is that the heart will be used, but donor sequence number correlates poorly with posttransplant outcomes. 3 In addition, donor hearts traditionally perceived as high risk, including those from hepatitis C virus–positive donors 4 and those with donation after circulatory death status, 5 are being considered as potentially suitable donor hearts. The evolving perception of acceptable donor hearts may lead centers to apply a more inclusive set of criteria for accepting hearts.…”

Systematic review: hepatitis C viraemic allografts to hepatitis C‐negative recipients in solid organ transplantation

“…Our initial search terms resulted in a set of 2186 articles, of which 35 studies satisfied the inclusion and exclusion criteria (Figure 1), 13‐46 including one paper identified with reference search 47 . There were 852 SOTs, which included 343 kidney, 233 heart, 204 liver and 72 lung transplants.…”

“… 25 A total of 12 deaths occurred. Five deaths were from primary graft failure, one death from graft dysfunction, 45 one from a pulmonary embolism, 26 one from disseminated bacteremia, 27 one from heart failure, 22 two deaths from necrotizing pancreatitis 39,46 and one death from multi‐organ failure with antibody‐mediated rejection 24 . None of the causes of death was reported to be specifically related to or associated with HCV transmission.…”

Hepatitis C viraemic organs in solid organ transplantation

“…9/11 (85%) developed detectable HCV viremia post-transplant and were started on SOF/ledipasvir (LDV) for 12 weeks (genotype 1) or SOF/VEL for 12-24 weeks (genotype 3) as an outpatient at a median 33 days posttransplant with 100% SVR12. Following this study, several other centers reported their own experiences with similar strategies 22,[26][27][28]35,36 . In total, this included 165 HCV-nonviremic recipients who received viremic hearts followed by surveillance NAT and treatment with J o u r n a l P r e -p r o o f various DAA regimens if positive.…”

“…However, this strategy has several potential barriers, including (1) payor approval of therapy prior to documented HCV transmission; (2) interruptions in therapy for patients requiring prolonged ventilation, however, in the largest, real-world prospective cohort this led to delay in initiation of therapy for median of 72 days for kidney recipients, 51 days for liver recipients, and 103 days for heart recipients with 2 cases of fibrosing cholestatic hepatitis due to HCV at 11 and 14 weeks posttransplant 35 . Given nearly 100% SVR 12 with regimens that are started post-transplant and given for 12 or more weeks and the high number of patients who required re-treatment with a second line DAA in the short prophylaxis regimens, our practice is to wait until patients become viremic post-transplant and treat for full 12 week course with regimen based on genotype and resistance testing, recognizing that the preliminary data with prophylactic strategy and of shorter duration (4-8 weeks) with G/P and SOF/VEL is promising 24,28,29,32,33,[36][37][38] .…”