Preemptive antiviral therapy in lung transplantation from hepatitis C donors results in a rapid and sustained virologic response

Mauricio A Villavicencio; Selena S Li; Ann Marie Leifer; Jenna L Gustafson; Asishana Osho; Stanley Wolfe; Yuval Raz; Jason Griffith; Isabel Neuringer; Emily Bethea; Thais Gift; Georgina Waldman; Todd Astor; Nathaniel B Langer; Raymond T Chung

doi:10.1016/j.xjon.2023.02.014

Preemptive antiviral therapy in lung transplantation from hepatitis C donors results in a rapid and sustained virologic response

JTCVS Open. 2023 Mar 10:14:602-614. doi: 10.1016/j.xjon.2023.02.014. eCollection 2023 Jun.

Authors

Affiliations

¹ Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn.
² Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Mass.
³ Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
⁴ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
⁵ Division of Pharmacology, Massachusetts General Hospital, Boston, Mass.

Abstract

Objective: The study objective was to assess the safety and efficacy of a preemptive direct-acting antiviral therapy in lung transplants from hepatitis C virus donors to uninfected recipients.

Methods: This study is a prospective, open-label, nonrandomized, pilot trial. Recipients of hepatitis C virus nucleic acid test positive donor lungs underwent preemptive direct-acting antiviral therapy with glecaprevir 300 mg/pibrentasvir 120 mg for 8 weeks from January 1, 2019, to December 31, 2020. Recipients of nucleic acid test positive lungs were compared with recipients of lungs from nucleic acid test negative donors. Primary end points were Kaplan-Meier survival and sustained virologic response. Secondary outcomes included primary graft dysfunction, rejection, and infection.

Results: Fifty-nine lung transplantations were included: 16 nucleic acid test positive and 43 nucleic acid test negative. Twelve nucleic acid test positive recipients (75%) developed hepatitis C virus viremia. Median time to clearance was 7 days. All nucleic acid test positive patients had undetectable hepatitis C virus RNA by week 3, and all alive patients (n = 15) remained negative during follow-up with 100% sustained virologic response at 12 months. One nucleic acid test positive patient died of primary graft dysfunction and multiorgan failure. Three of 43 nucleic acid test negative patients (7%) had hepatitis C virus antibody positive donors. None of them developed hepatitis C virus viremia. One-year survival was 94% for nucleic acid test positive recipients and 91% for nucleic acid test negative recipients. There was no difference in primary graft dysfunction, rejection, or infection. One-year survival for nucleic acid test positive recipients was similar to a historical cohort of the Scientific Registry of Transplant Recipients (89%).

Conclusions: Recipients of hepatitis C virus nucleic acid test positive lungs have similar survival as recipients of nucleic acid test negative lungs. Preemptive direct-acting antiviral therapy results in rapid viral clearance and sustained virologic response at 12 months. Preemptive direct-acting antiviral may partially prevent hepatitis C virus transmission.

Keywords: antivirals; hepatitis C; lung transplantation; outcomes.

Publication types

Clinical Trial