Short-course prophylaxis with the Toronto HCV protocol for recipients of non-liver solid organ transplants from donors with hepatitis C viraemia: a retrospective, matched cohort study.

Authors

Wesam Aleyadeh, Marcelo Cypel, S Joseph Kim, Michael A McDonald, Jeffrey Schiff, Ana Carolina Alba, Shaf Keshavjee, Kaijo Yacht, Dipika Munyal, Rhonda Allan, June Wang, Deepali Kumar, Atul Humar, Jordan J Feld

Published in

The lancet. Gastroenterology & hepatology. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Organs from donors positive for hepatitis C virus (HCV) nucleic acid testing (NAT-positive) expand the non-liver solid organ donor pool. Standard post-transplantation direct-acting antiviral therapy requires an 8-12-week course, which might add logistical, financial, and pharmacological complexity. We therefore aimed to evaluate long-term follow-up from an initial pilot trial and outcomes after adoption of the short-course Toronto HCV protocol as the institutional standard of care in HCV-negative recipients of organs from HCV viraemic donors.
This retrospective, matched cohort study was conducted at a single transplant centre at Toronto General Hospital (Toronto, ON, Canada). Eligible patients were HCV NAT-negative recipients (aged ≥18 years) who received kidney, kidney-pancreas, pancreas, heart, or lung transplants from an HCV NAT-positive donor (aged <70 years). Recipients were categorised into the initial cohort (received treatment during the initial pilot study; n=30) and standard of care cohort (received treatment after institutional adoption of the Toronto HCV protocol on Jan 9, 2020; n=86). The Toronto HCV protocol consists of oral glecaprevir 300 mg/day and pibrentasvir 120 mg/day and oral ezetimibe 10 mg/day for 8 days. The first dose is administered 6-12 h before transplantation for 8 days (one pretransplantation dose and seven post-transplantation doses). Data were abstracted from electronic medical records. Each donor-positive, recipient-negative (D+R-) recipient of kidney, lung, and heart transplants was matched with up to four donor-negative, recipient-negative (D-R-) controls based on organ type, sex, age, transplantation date, and primary disease. The primary outcome was undetectable HCV RNA at 12 weeks post-transplantation or at the latest documented assessment for recipients who died before that timepoint. Secondary outcomes were 2-year overall survival, graft function at 1 year (mean estimated glomerular filtration rate [eGFR], mean forced expiratory volume in 1 s [FEV]₁, and left ventricular ejection fraction <40%), and safety. Survival was compared between D+R- recipients and matched D-R- controls separately for each organ type using a Cox proportional hazards regression model stratified by matched set.
Between Feb 4, 2019, and Dec 31, 2024, 116 D+R- non-liver solid organ transplantations were performed using organs from 72 unique HCV NAT-positive donors: 56 (48%) kidney, 34 (29%) lung, 16 (14%) heart, six (5%) kidney-pancreas, and four (3%) pancreas transplants. The mean recipient age was 54·6 years (SD 14·4). 79 (68%) recipients were male and 37 (32%) were female. The matched D-R- cohort consisted of 168 kidney, 103 lung, and 16 heart transplant recipients (matching was not done for other organs due to small numbers). All 116 (100%) D+R- recipients met the primary endpoint; 114 (98%) recipients had documented undetectable HCV RNA at 12 weeks post-transplantation and two (2%) recipients who died before 12 weeks had undetectable HCV RNA at the latest assessment before death. 25 (22%) deaths occurred during a median follow-up of 140 weeks (IQR 46-212). 2-year overall survival was 83·9% (95% CI 74·6-90·0) among the 106 kidney, lung, and heart recipients; no deaths occurred among the ten pancreas or kidney-pancreas recipients. Within each organ group, there was no difference in 2-year overall survival between D+R- and D-R- recipients for kidney (93·5% [95% CI 81·1-97·9] vs 94·8% [89·8-97·4]; hazard ratio [HR] 1·50 [95% CI 0·38-6·00], p=0·57), lung (70·6% [50·9-83·5] vs 78·7% [68·8-85·7]; HR 1·62 [0·70-3·73], p=0·26), or heart (81·3% [52·5-93·5] vs 81·3% [52·5-93·5]; HR 3·00 [0·31-28·84], p=0·34) transplants. Graft function at 1 year was similar between D+R- and D-R- recipients (mean eGFR 63·9 mL/min per 1·73m² [SD 22·2] vs 57·4 mL/min per 1·73m² [20·9], p=0·24; mean FEV₁ 2·18 L [SD 0·87] vs 2·29 L [0·85], p=0·59; and left ventricular ejection fraction <40% in one [6%] vs three [19%], p=0·60). No HCV-related complications were reported and there were no treatment-related deaths, treatment discontinuations, dose modifications, or clinically significant drug-drug interactions. One (1%) grade 3 elevation in alanine aminotransferase in a kidney recipient was deemed possibly related to treatment. Laboratory tests for cause of liver injury in this patient were unrevealing and liver biopsy showed non-specific acute hepatitis with moderate steatosis and no fibrosis.
The Toronto HCV protocol prevented or rapidly cleared HCV infection in D+R- recipients of non-liver solid organ transplants, with no difference in overall survival versus matched D-R- controls. This short-course approach offers a practical, lower cost alternative to standard post-transplantation antiviral regimens and supports routine use of organs from donors with HCV viraemia.
None.

PMID:
42810376
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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