Encouraging results from case series suggest it is medically feasible to transplant kidneys from hepatitis C (HCV)-positive donors to HCV-negative recipients by using direct-acting antivirals (DAAs), but the optimal timing and duration of DAA therapy still needs to be determined. Meanwhile, a survey of clinicians identifies a number of barriers to widespread adoption of HCV-viremic kidney transplantation to uninfected recipients.
In the REHANNA trial (Renal Transplants in Hepatitis C Negative Recipients With RNA Positive Donors; NCT03627299), Christine M. Durand, MD, and colleagues from Johns Hopkins School of Medicine in Baltimore, Maryland, tested a novel protocol of 4-week DAA prophylaxis for kidney transplantation from 10 deceased donors (aged 13 to 55 years) who tested positive for HCV nucleic acid to 10 adult recipients free of HCV, HIV, active hepatitis B virus, and liver disease. Recipients received a pangenotypic combination of glecaprevir (300 mg) and pibrentasvir (120 mg). The first dose was administered before organ perfusion, followed by 1 dose daily for 4 postoperative weeks.
HCV RNA was undetectable in all recipients after day 7, Dr Durand’s team reported in the Annals of Internal Medicine.
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No recipient had grade 3 or higher treatment-related adverse events or aminotransferase or bilirubin levels 2.5 times the upper limit of normal or more. At 12 weeks, the estimated glomerular filtration rate (eGFR) ranged from 30 to 79 mL/min/1.73 m2. One graft failed at day 261 due to venous thrombosis unrelated to HCV or DAA therapy. No rejection episodes occurred, and no patients died over 12 months of follow-up.
The first prophylaxis trial, EXPANDER (Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-Negative Recipients), previously showed that 12 weeks of grazoprevir-elbasvir was effective. A trial of very short-term prophylaxis failed: In DaPPER (Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients), HCV transmission occurred despite 1 dose of sofosbuvir-velpatasvir being administered before transplant and 1 to 3 doses given afterward. The opposite approach – transplant the HCV kidney then treat – explored in THINKER (Trial of Transplantation of HCV-Infected Kidneys Into Uninfected Recipients) led to complications, such as transaminitis, donor-specific antibodies, rejection, BK and cytomegalovirus viremia, and fibrosing cholestatic hepatitis.
According to Dr Durand’s team, “our study provides important proof of concept that HCV D+/R- kidney transplantation with 4-week DAA prophylaxis may prevent recipient HCV infection and shorten wait times.”
Challenges to adoption of HCV-viremic kidney donation
In a separate Kidney360 study, Krista L. Lentine, MD, PhD, of Saint Louis University Transplant Center in St. Louis, Missouri, and colleagues gauged attitudes, management strategies, and barriers with respect to the use of HCV-viremic donor organs in uninfected recipients. The team conducted the first national survey of staff at 112 transplant programs representing 54% of programs in the United States and 69% of adult deceased donor kidney transplant volume in 2019. Nearly half of respondents were transplant nephrologists (46%) or surgeons (43%).
Only 58% of responders reported that their programs offer HCV-positive donor kidney transplant to HCV-negative recipients, including 35% under clinical protocols, 14% as standard of care, and 9% under research protocols. Half of respondents only start DAA therapy after hospital discharge and viremia is documented, when recipients’ insurance programs are more likely to pay for the therapy. Slightly more than half of programs performing these transplants provide DAA therapy when insurance denies payment, according to survey results.
Survey respondents believed HCV-positive donor kidney transplants to uninfected recipients are justified if transplant waiting times are reduced by more than 18 months. But staff still voiced concerns, including lack of insurance coverage (72%), high costs (60%), and perceived risk of transmitting treatment-resistant infections (44%).
“Despite the published outcomes in clinical studies, the development of safe and effective strategies to utilize [HCV nucleic acid-positive] organs is challenging,” Dr Lentine’s team wrote. “Safe transplantation requires coordination to ensure universal posttransplant testing, access to DAAs for viremic patients, and appropriate monitoring to ensure compliance and viral clearance.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original references for a full list of authors’ disclosures.
References
Durand CM, Barnaba B, Yu S, et al.Four-week direct-acting antiviral prophylaxis for kidney transplantation from hepatitis C–viremic donors to hepatitis C–negative recipients: an open-label nonrandomized study. Ann Intern Med. Published online September 7, 2020. doi:10.7326/M20-1468
Lentine KL, Peipert JD, Alhamad T, et al. Survey of clinician opinions on kidney transplantation from hepatitis-C virus-positive donors: identifying and overcoming barriers. Kidney360. September 2020. doi:10.34067/KID.0004592020
