An eight-day antiviral course let hepatitis C-positive organs go to uninfected patients

Thousands of transplantable organs are discarded each year because their donors carried hepatitis C, even though modern antiviral drugs cure the infection almost universally. The usual approach is to transplant the organ and then treat the recipient for eight to twelve weeks — effective, but costly and logistically heavy. Clinicians at Toronto General Hospital have pushed the idea further: give a much shorter antiviral course starting just before surgery, as prophylaxis rather than treatment. A new report on their "Toronto HCV protocol" describes what happened once that short course became the hospital's standard practice [s1].

What the study did

This was a retrospective, matched cohort study at a single centre, not a randomised trial — an important limit to bear in mind [s1]. It covered hepatitis C-negative adults who received a kidney, kidney-pancreas, pancreas, heart, or lung transplant from a donor who tested positive for hepatitis C viral material [s1]. The protocol is strikingly brief: oral glecaprevir and pibrentasvir (two direct-acting antivirals) plus ezetimibe for eight days, with the first dose given 6 to 12 hours before transplantation and seven doses after [s1]. Between February 2019 and December 2024, 116 such transplants were performed using organs from 72 infected donors — 56 kidney (48%), 34 lung (29%), 16 heart (14%), and ten pancreas or kidney-pancreas (8%) [s1]. The recipients spanned two periods: an initial pilot cohort of 30 patients and a larger group of 86 treated after the protocol became the hospital's standard of care in January 2020 [s1]. Their mean age was 54.6 years, and 68% were men [s1]. Each infected-donor recipient was matched with up to four comparable patients who received organs from uninfected donors, yielding matched comparison groups of 168 kidney, 103 lung, and 16 heart recipients [s1]. The funding line is notable for a transplant study: none [s1].

What it found

Every recipient cleared the hurdle the protocol was designed for. All 116 (100%) met the primary endpoint of undetectable hepatitis C RNA at 12 weeks or at their last assessment; 114 (98%) had confirmed undetectable virus at the 12-week mark, and the two others died of unrelated causes before then with no detectable virus [s1]. Over a median follow-up of 140 weeks, 25 recipients (22%) died — a reminder that these are gravely ill patients regardless of donor status [s1]. Two-year overall survival was 83.9% across the kidney, lung, and heart recipients [s1]. Crucially, survival did not differ between those who got infected-donor organs and matched recipients of uninfected organs: for kidneys, 93.5% versus 94.8%; for lungs, 70.6% versus 78.7%; for hearts, 81.3% versus 81.3%, with none of the differences statistically significant [s1]. Graft function at one year was also comparable: average kidney filtration rates were 63.9 versus 57.4 mL/min per 1.73m², and average lung function (FEV1) was 2.18 versus 2.29 litres, neither difference statistically significant [s1]. On safety, there were no hepatitis C-related complications and no treatment-related deaths or discontinuations; a single recipient (1%) had a liver-enzyme rise possibly linked to the drugs [s1].

How to read it

The clinical signal is strong and the design is weak, and both statements are true at once. A 100% primary-endpoint success rate and survival that tracks uninfected-donor controls make a persuasive case that short-course prophylaxis works [s1]. But this is observational evidence from one hospital, not a randomised comparison, so unmeasured differences between who received which organ cannot be ruled out. The survival comparisons within each organ type rest on small numbers, which is why their confidence intervals are wide — the heart analysis, for instance, spans a hazard ratio from 0.31 to 28.84 [s1]. The honest reading is that the data cannot detect anything but a large survival penalty, and they find none.

What makes the finding matter is the resource argument. If eight days of prophylaxis is as safe as eight-to-twelve weeks of treatment, more infected-donor organs can be used at lower cost and complexity, expanding a desperately short supply [s1]. Shortening the drug course also reduces the window for drug interactions and the out-of-pocket burden on patients, both of which matter in the fragile early weeks after a transplant. That is a reason to run the randomised trials this cohort cannot substitute for. Related coverage has examined a trial of eight-week antiviral therapy in chronic hepatitis C and why Europe is off track on hepatitis elimination.

What to watch

The study authors position the eight-day regimen as a practical standard of care; the field will want confirmation from multi-centre, ideally randomised, work and longer follow-up before it becomes routine everywhere [s1][s2].

This article describes research and is not medical advice. Transplant decisions are a matter for patients and their transplant teams.

Sources

• Short-course prophylaxis with the Toronto HCV protocol for non-liver organ transplant recipients — The Lancet Gastroenterology & Hepatology, 29 September 2026
• Toronto HCV protocol pilot trial registration (NCT04017338) — ClinicalTrials.gov