Real-world Experiences in the Transplantation of Hepatitis C-NAAT–positive Organs

Background. Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)–positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients with donor-derived HCV infection without significant adverse effects, although variability remains in the timing and duration of antivirals. Methods. This retrospective study analyzed all adult HCV-NAAT–negative transplant recipients who received an organ from HCV-NAAT–positive donors from November 24, 2018, to March 31, 2022, at Duke University Medical Center with protocolized delay of DAA initiation until after hospital discharge, with at least 180-d follow-up on all patients. Transplant and HCV-related outcomes were analyzed. Results. Two hundred eleven transplants (111 kidneys, 41 livers, 34 hearts, and 25 lungs) were performed from HCV-NAAT–positive donors to HCV-NAAT–negative recipients. Ninety percent of recipients became viremic within 7 d posttransplant. Ninety-nine percent of recipients were initiated on pangenotypic DAAs in the outpatient setting a median of 52 d posttransplant, most commonly with 12-wk courses of sofosbuvir–velpatasvir (lungs) and glecaprevir–pibrentasvir (heart, kidney, and liver). Ninety-seven percent of recipients had SVR after a first-line DAA; all ultimately achieved SVR at 12 wk after subsequent treatment courses. The median peak HCV RNA for all organ systems was 2 436 512 IU/mL; the median time from antiviral to undetectable RNA was 48 d, although differences were noted between organ groups. No patient deaths or graft losses were directly attributable to HCV infection. Conclusions. One hundred percent of transplant recipients of HCV-NAAT–positive organs ultimately developed SVR without significant adverse effects when HCV antivirals were initiated in the outpatient setting after transplant hospitalization, suggesting that this real-world treatment pathway is a viable option.

[1]  S. Naggie,et al.  Antiviral Treatment Failures After Transplantation of Organs From Donors With HCV Infection: A Report of 4 Cases. , 2023, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[2]  K. Washburn,et al.  Kidney transplant from hepatitis C viremic donors into aviremic recipients and risk for post‐transplant BK and cytomegalovirus infection , 2022, Transplant infectious disease : an official journal of the Transplantation Society.

[3]  J. Friedewald,et al.  One-Year Outcomes of the Multi-Center StudY to Transplant Hepatitis C-InfeCted kidneys (MYTHIC) Trial , 2021, Kidney international reports.

[4]  R. Chung,et al.  Association of donor hepatitis C virus infection status and risk of BK polyomavirus viremia after kidney transplantation , 2021, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[5]  R. Barth,et al.  The Impact of Treatment Delay on Hepatitis C Liver Transplant Outcomes , 2021, Journal of pharmacy practice.

[6]  R. Sterling,et al.  Outcomes of short‐duration antiviral prophylaxis for hepatitis C positive donor kidney transplants , 2021, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  N. Narula,et al.  Increased early acute cellular rejection events in hepatitis C-positive heart transplantation. , 2020, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[8]  C. Quintini,et al.  Hepatitis C Virus NAT‐Positive Solid Organ Allografts Transplanted Into Hepatitis C Virus–Negative Recipients: A Real‐World Experience , 2020, Hepatology.

[9]  Udobi C. Campbell,et al.  Clinical pharmacy programmatic perspectives on use of direct-acting antivirals for acquired hepatitis C infection in solid organ transplant recipients. , 2020, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[10]  H. Dahari,et al.  Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study. , 2020, The lancet. Gastroenterology & hepatology.

[11]  R. Sterling,et al.  Ultra‐short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients , 2020, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[12]  M. Buti,et al.  Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: the EXPEDITION-8 trial. , 2020, Journal of hepatology.

[13]  M. Molnar,et al.  Transplantation of kidneys from hepatitis C–infected donors to hepatitis C–negative recipients: Single center experience , 2019, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[14]  K. Reddy,et al.  Early emergence of anti‐HCV antibody implicates donor origin in recipients of an HCV‐infected organ , 2019, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[15]  P. Camp,et al.  Heart and Lung Transplants from HCV‐Infected Donors to Uninfected Recipients , 2019, The New England journal of medicine.

[16]  R. Hasz,et al.  Twelve-Month Outcomes After Transplant of Hepatitis CInfected Kidneys Into Uninfected Recipients , 2018, Annals of Internal Medicine.

[17]  P. Angus,et al.  Glecaprevir/Pibrentasvir Treatment in Liver or Kidney Transplant Patients With Hepatitis C Virus Infection , 2018, Hepatology.

[18]  D. Segev,et al.  Direct-Acting Antiviral Prophylaxis in Kidney Transplantation From Hepatitis C VirusInfected Donors to Noninfected Recipients , 2018, Annals of Internal Medicine.

[19]  T. Asselah,et al.  Glecaprevir–Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection , 2018, The New England journal of medicine.

[20]  S. Mohanty,et al.  Diagnosis and Management of Hepatitis C Infection in Primary Care Settings , 2018, Journal of General Internal Medicine.

[21]  K. Patel,et al.  Genotype 3 Infection: The Last Stand of Hepatitis C Virus , 2017, Drugs.

[22]  T. Asselah,et al.  Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. , 2015, The New England journal of medicine.

[23]  T. Berg,et al.  Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. , 2015, The New England journal of medicine.

[24]  Stefan Zeuzem,et al.  Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. , 2014, The New England journal of medicine.

[25]  D. Lanfear,et al.  High rates of false-positive hepatitis C antibody tests can occur after left ventricular assist device implantation. , 2013, ASAIO journal.

[26]  E. Cantu,et al.  Hepatitis B Core Antibody Positive Donors as a Safe and Effective Therapeutic Option to Increase Available Organs for Lung Transplantation , 2005, Transplantation.

[27]  Treatment of HCV-Uninfected Transplant Recipients Receiving Organs From HCV-Viremic Donors , 2020 .

[28]  L. Vasovic,et al.  False positive hepatitis C antibody test results in left ventricular assist device recipients: increased risk with age and transfusions. , 2017, Journal of thoracic disease.

[29]  M. Serper,et al.  DIVISION OF GASTROENTEROLOGY , 2009 .

[30]  Don Zoellner,et al.  National data. , 1992, Occasional paper.