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

Transplantation of Livers of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa®)

This is an open-label, pilot trial to test the safety and efficacy of transplantation of livers from Hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the liver transplant waitlist. Treatment and prophylaxis will be administered, using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

Study Overview

• Status: Completed
• Conditions: Hepatitis C; Liver Transplant
• Intervention / Treatment: Drug: sofosbuvir/velpatasvir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HCV seropositive non-viremic (HCV Ab+/NAT-) donor; Liver recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated. Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).	Drug: sofosbuvir/velpatasvir; 12 week, oral, fixed dose; Other Names: Epclusa
Experimental: HCV seropositive viremic (HCV Ab+/NAT+) donor; Post-operative day 1, liver recipients will be treated with 12-week oral course of sofosbuvir/ velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).	Drug: sofosbuvir/velpatasvir; 12 week, oral, fixed dose; Other Names: Epclusa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events Due to Sofosbuvir/Velpatasvir (Epclusa)	Adverse events due to sofosbuvir/velpatasvir (Epclusa)	5 years
HCV Free at 1 Year Following Transplantation		1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transmission Rate of HCV From HCVAb+/NAT- Donors to HCVAb- Recipients		5 years
Incidence of Allograft Rejection at 5 Years		5 years
Incidence of Graft Loss at 5 Years		5 years
All-cause Mortality at 5 Years		5 years
Waitlist Time After Enrollment	In days	5 years

Collaborators and Investigators

• Sponsor: Fernanda P Silveira, MD, MS
• Collaborators: University of Pittsburgh Medical Center
• Investigators: Study Director: Fernanda Silviera, MD, University of Pittsburgh; Principal Investigator: Naudia Jonassaint, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2019
• Primary Completion (Actual): March 17, 2025
• Study Completion (Actual): March 17, 2025

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; Flaviviridae Infections; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; sofosbuvir-velpatasvir drug combination
• Other Study ID Numbers: STUDY19100082

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not plan to share individual patient data outside of our investigative team. Aggregate data will be shared in publications as appropriate.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No