The Study of Hepatitis Eradication Receiving Protease Inhibitor Administration

4. STUDY PROCEDURES 4.1 Subject Enrollment The patient is considered to be enrolled when they sign study consent. This may be months or years prior to the date of transplantation and therefore all study patients will be asked to affirm consent at the time of transplantation. There are 2 non-randomized study groups: Those patients who receive a non-HCV donor and those who receive a donor with HCV infection. Subjects will re-sign the consent on the line reserved for this purpose at the time of the transplant.

If the patient presented with a hepatitis C donor heart decides not to take that heart, they would remain in the study and when a suitable heart is found (infected or not), they would be followed post-transplant in the study.

4.2 Study Procedures Following transplantation with an HCV infectious donor, HCV viral load (RNA assay) will be measured at days 3,7 and 14 days post-transplant. The HCV viral load assay is a routine FDA cleared laboratory test which is one of the standard labs available at Sentara Norfolk General Hospital. It involves a blood sample of 5 cc which is then processed in the lab. Based on prior work, it is likely that all transplant recipients with infectious donors will seroconvert within this time frame. If these patients remain negative for HCV RNA, it will be rechecked every month for a total of 6 months. This routine testing is covered by insurance as this is the clinical standard for donors with elevated risk (Public Health Service increased risk).

Once a patient seroconverts to HCV positive, insurance authorization for treatment will be sought for treatment with glecaprevir/pibrentasivir. Based on input from Dr. Michael Ryan of Gastroenterology, insurance carriers are approving therapy given the noted efficacy, low comparative cost and the recent FDA approval of this drug in renal and liver transplant recipients. The study treatment is oral glecaprevir/pibrentasivir, 3 tablets daily with food, for a total of 12 weeks. The medication will be paid by the patient's insurance prescription coverage.

Serial measurements of HCV NAT (every month) will be conducted including through 24 weeks post-transplant. In addition, coronary angiography plus coronary intravascular ultrasound will be conducted at 6-12 weeks post-transplant and at one-year post transplant which will allow careful evaluation for cardiac allograft vasculopathy. Of note, it has been the policy of the Sentara Heart Transplant program for more than 5 years to perform baseline (early post-transplant) and annual coronary angiography and coronary intravascular ultrasound, and regardless of study participation, all patients will undergo this standard of care surveillance.