A groundbreaking clinical trial is underway in France, exploring an innovative surgical method known as the RAPID procedure, which has the potential to transform liver transplantation for patients with hepatocellular carcinoma (HCC). This novel approach aims to address the persistent challenges of organ shortage and prolonged waiting times that currently plague liver transplant candidates. By adopting a technique involving the resection and partial transplantation of split deceased donor livers, the RAPID procedure seeks to expand graft availability while improving patient survival outcomes.
Hepatocellular carcinoma, the most common primary liver cancer, often strikes patients who retain relatively preserved liver function. Despite advances in cancer therapy, liver transplantation remains a cornerstone treatment for early-stage HCC, conferring improved survival and disease control. Yet, the gap between transplant demand and available organs forces many patients into extended waiting periods, with increased risk of tumor progression and mortality. The RAPID-HCC trial, a prospective, multicenter study spanning five top university hospitals in France, was conceived to rigorously evaluate whether the RAPID procedure can break these barriers.
At the heart of this innovative surgical technique lies the concept of split liver transplantation from deceased donors. Traditionally, whole liver grafts from brain-dead donors are transplanted into recipients. However, the RAPID procedure divides one donor liver into two segments, enabling simultaneous transplantation into two adult recipients. The trial specifically enrolls adult HCC patients with preserved liver function, defined by MELD scores of 15 or below, to receive the left lateral lobe (segments II and III) as a living graft replacement for their marginal native liver.
The surgical process of the RAPID procedure unfolds in a meticulously timed two-phase operation. Initially, the donor’s left lateral segment is meticulously split and transplanted to replace the recipient’s left liver lobe, while the patient’s native right liver lobe remains intact to sustain hepatic function. This partial augmentation provides immediate functional support, allowing the patient’s physiology to adapt gradually. After a period of roughly four months, the native right lobe is removed in a delayed sequential hepatectomy, effectively transitioning the graft to full function.
Trial enrolment targets 50 adult HCC patients, among whom 34 are designated to undergo the RAPID procedure with split liver grafts. This multicentric study adopts rigorous criteria for patient selection and perioperative care to assess not only feasibility but also safety, tolerance, and overall efficacy. Primary endpoints focus on successful completion of both surgical stages and incidence of adverse events, while secondary measures examine crucial outcomes such as graft survival, patient survival, incidence of rejection, HCC recurrence, and comparative waiting times versus conventional whole liver transplantation.
Prior observational studies have hinted at the potential benefits of the RAPID technique. By maximizing the utility of a single donor organ among two recipients, the method significantly bolsters graft availability, potentially curtailing the current organ deficit crisis. For patients, this could translate into shorter waiting times, earlier transplantation, and consequently lower risk of tumor progression or dropout from the transplant list. However, quantitative evidence from robust prospective trials such as RAPID-HCC remains necessary to validate these promising early indications.
The RAPID-HCC trial carries profound implications for transplant medicine, especially for patients with HCC who are often caught in the precarious balance between liver function reserve and cancer progression. By targeting patients with preserved liver function, the trial leverages their native hepatic support as a safety buffer during the transplantation transition. This strategic approach contrasts with traditional transplant methodologies that replace the entire liver simultaneously, thereby potentially reducing surgical risk and postoperative complications.
Crucially, the delayed total hepatectomy aspect offers a novel pathway for the transplanted graft to gradually assume full functional responsibility. By staging the liver removal process, the patient’s hepatocyte function adapts progressively, minimizing risks associated with sudden hepatic failure or graft insufficiency. The physiological dynamics underpinning this gradual shift are being closely monitored through the study, offering valuable mechanistic insights into liver regeneration and adaptation post-transplant.
The prospective, non-randomized design across multiple high-volume centers in France ensures that data emerging from RAPID-HCC will reflect real-world applicability with diverse surgical teams and patient populations. Rigorous follow-up protocols will capture clinical outcomes including patient survival at various time points, graft function, rejection episodes governed by immunological assays, and cancer recurrence monitored via imaging and biomarkers. The wealth of data will help delineate the exact performance metrics and potential complications inherent to this new surgical paradigm.
While the RAPID technique offers exciting opportunities, challenges remain. Technical complexity in splitting the liver graft and orchestrating two separate yet coordinated surgeries demands high surgical expertise and interdisciplinary coordination. Additionally, close management of immunosuppressive therapy and vigilant monitoring for rejection phenomena are necessary to safeguard graft longevity. The trial’s comprehensive protocol is designed to address these intricacies through standardized operative and postoperative care pathways.
If successful, RAPID-HCC could redefine the transplant landscape, setting a new standard of practice by systematically expanding donor liver utilization and reducing mortality among HCC candidates. Moreover, the principles underpinning this approach may extend beyond HCC to other liver diseases amenable to partial transplantation strategies, magnifying its clinical impact globally.
This investigation is backed by the French national PHRC-K Inca 2020 grant, marking a significant investment in innovative liver transplant research. Registered under ClinicalTrials.gov (NCT05971628) before patient recruitment commenced, the trial exemplifies rigorous scientific transparency and adherence to ethical research standards. The consortium of transplant surgeons, oncologists, and hepatologists driving RAPID-HCC is poised to pioneer a transformative chapter in hepatic oncology and transplantation.
Ultimately, the RAPID procedure embodies a fusion of surgical ingenuity and clinical necessity, striving to reconcile the glaring mismatch between organ demand and supply. Its focus on timed, partial transplantation with delayed total hepatectomy creates a dynamic clinical model that balances risk, function, and oncologic control. As data accrues from this landmark trial, the transplant community worldwide keenly anticipates validation that could usher in a new era of liver transplant strategy for HCC patients.
In a field where innovation is deeply intertwined with patient survival, the RAPID-HCC trial is a beacon of hope—offering a pragmatic solution to one of the most stubborn bottlenecks in transplant medicine. Its pioneering approach challenges traditional doctrines, harnessing split grafts not only to increase organ availability but also to improve functional outcomes, thereby reshaping the future for thousands waiting for life-saving liver transplants.
As transplantation science progresses, studies like RAPID-HCC underscore the critical importance of adaptive surgical techniques informed by robust clinical trials. With liver cancer incidence rising globally and organ scarcity worsening, the timely results from this trial will be pivotal in guiding policies, surgical practices, and patient care pathways on a global scale.
The RAPID procedure is poised to become more than a novel technique; it represents a potential paradigm shift in how surgeons and clinicians approach one of the deadliest liver diseases. By expanding the boundaries of partial transplantation through staged hepatectomy, the method elegantly integrates regenerative biology with surgical precision, ultimately aiming to save lives and improve quality of life for patients with hepatocellular carcinoma.
Subject of Research: Liver transplantation for hepatocellular carcinoma using the RAPID procedure involving resection and partial liver transplantation from deceased donors.
Article Title: Resection and partial liver transplantation from deceased donors with delayed total hepatectomy (RAPID procedure) for hepatocellular carcinoma: a national, multicenter, non-randomized, prospective trial
Article References:
Peloso, A., Pietrasz, D., Daillier, E. et al. Resection and partial liver transplantation from deceased donors with delayed total hepatectomy (RAPID procedure) for hepatocellular carcinoma: a national, multicenter, non-randomized, prospective trial. BMC Cancer 25, 848 (2025). https://doi.org/10.1186/s12885-025-14127-7
Image Credits: Scienmag.com
