The Use of Hepatitis C Positive Livers in Hepatitis C Negative Liver Transplant Recipients

This is a prospective, single center, pilot, open-label study of transplantation of livers of
HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir
(Epclusa®). Recipients of a liver from HCVAb+/NAT- donors will be in arm 1 (the
transmission-triggered arm) of the study. In this arm, the study will monitor transmission of
HCV by measuring HCV RNA in liver transplant recipients. If HCV RNA is detected, indicating
transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12
weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after
completion of therapy.

Recipients of a liver from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the
study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir
(Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for
evidence of transmission.

To be eligible for the study, subjects need to be listed for liver transplantation, be not
infected with HCV, HBV or HIV, and sign informed consent.

Inclusion criteria (recipients):

1. Patients with end-stage liver disease listed for liver transplantation at UPMC.

2. Age ≥ 18

3. No available living liver donor

4. Listed for an isolated liver transplant at UPMC

5. Have panel reactive antibody level of <98%

6. Able to travel to UPMC for routine post-transplant visits and study visits for a
minimum of 12 months after transplantation

7. Able to provide informed consent

8. Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

1. HIV positive

2. HCVAb or HCV RNA positive

3. Presence of behavioral risk factors for contracting HCV. These behavioral risk factors
are current injection drug use, current intranasal illicit drug use, current
percutaneous/parenteral exposures in an unregulated setting.

4. Hepatitis B surface antigen positive

5. History of atrial fibrillation requiring the use of amiodarone over the past 12m

6. Receipt of prior organ transplant

7. Waitlisted for a multi-organ transplant

8. Pregnant women

9. Known allergy to sofosbuvir/velpatasvir

10. Any condition, psychiatric or physical, that in the opinion of the investigator would
make it unsafe to proceed with transplantation or interfere with the ability of the
subject to participate in the study

Inclusion criteria (donors):

1. HCV antibody positive

2. HCV NAT negative or positive

Exclusion criteria (donors):

1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24
antigen and/or positive HIV NAT)

2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)

3. Known ongoing therapy for HCV