Resection and partial liver transplantation from deceased donors with delayed total hepatectomy (RAPID procedure) for hepatocellular carcinoma: a national, multicenter, non-randomized, prospective trial

Abstract

Background: This trial wants to ascertain whether the RAPID procedure could improve graft availability and patient survival in hepatocellular carcinoma (HCC) setting. RAPID-HCC trial, which aims to decrease waiting times and mortality for patients on the transplant list by adopting a novel surgical approach, could be a major step forward in liver transplantation (LT). If successful, the RAPID procedure could become a new standard of care for LT, addressing the critical shortage of organs and improving outcomes for selected patients with early-stage HCC. We expected to provide critical evidence to support the wider adoption of this new approach.

Methods: The RAPID-HCC trial is a prospective, multicentre study conducted across five major university hospitals in France aiming to assess the feasibility, safety, tolerance, and efficacy of the RAPID procedure on HCC patients. A total of 50 adult HCC patients with preserved liver function (MELD score ≤ 15) will be enrolled and 34 of these will receive a split liver graft from a brain-dead donor (DBD). The RAPID procedure consists in splitting a deceased donor liver and transplanting it into two adult recipients. The operation consists of two phases: first, the donor's left lateral lobe (G23) replaces the recipient's left liver lobe (H1234), while the native right lobe stays to support hepatic function. The recipient's right lobe (H5678) is removed four months later, leaving the graft fully functional. Primary outcomes will focus on the feasibility and safety of the procedure, assessed by successful completion of both surgical stages and monitoring for adverse events. Secondary outcomes will include graft and patient survival, incidence of rejection and HCC recurrence, waiting times and overall patient outcomes compared to conventional whole liver transplantation.

Discussion: Early insights from several studies hint that the RAPID method might improve graft availability and recipient survival. Still, further studies are needed to confirm these benefits, especially for HCC patients. RAPID HCC trial pushes forward liver transplants for HCC patients who still have good liver function. This method could reduce waiting times and mortality in transplant candidates. If successful, the RAPID procedure could be adopted as a new standard for LT. TRIAL REGISTRATION {2A} {2B}: ClinicalTrials.gov NCT05971628. Registered on August 2, 2023, before the start of inclusion. Project Code: APHP210351 / N° IDRCB: 2022-A02151-42.

Grant support: This study was supported by the French national PHRC-K Inca 2020.

Keywords: Auxiliary liver transplantation; Delayed hepatectomy; Graft split; HCC; Partial liver transplantation; Two stages hepatectomy.

Fig. 1

Two stages of RAPID protocol. First Stage: In case of left-sided HCC, left hepatectomy (H1234) will be performed and the native left liver will be replaced with the RAPID small graft (G23), while the native right liver will be left intact. In case of right-sided HCC, the HCC must have been pre-operatively controlled by TACE or thermoablation technic. If persistent tumour activity in the right liver despite preoperative treatment, limited resection/radioablation of active HCC will be performed concomitantly with the left hepatectomy. This is followed by a left hepatectomy including resection of the Spiegel lobe (H1234) and the terminal branches of the middle hepatic vein to allow subsequent anastomosis of the common venous trunks. The native right liver will not be mobilized. Second Stage: A right hepatectomy (H5678) will be carried out using the same abdominal incision

Fig. 2

Left lobe split-liver graft and graft implantation. A Anatomical aspect of the left lobe split-liver graft. The common portal trunk, complete arterial hepatic trunk and left hepatic duct are preserved. The suprahepatic anatomy includes the common venous trunk with left hepatic vein and the origin of the median vein. B The RAPID graft implantation involves (in color the graft, in grey the recipient): venous anastomosis between the common venous trunks; portal anastomosis between the donor portal vein and the recipient portal vein (preferably avoiding the left portal branch), ideally in a side-to-end fashion; arterial anastomosis between the celiac trunk of the graft to the common (or proper) hepatic artery or the stump of left hepatic artery or splenic artery of the recipient; biliary anastomosis with an hepaticojejunostomy between the left biliary duct and jejunum with a R-and-Y reconstruction

Fig. 3

RAPID-HCC trial timeline chart. The RAPID-HCC Protocol includes the following phases: Selection (0–6 months, informed consent); Pre-Transplant Evaluation (6–12 months, imaging and serology); Inclusion Validation (12–13 months, committee approval); Pre-Surgical Follow-Up (13–18 months, routine checks); First Surgery (18–19 months, partial hepatectomy with auxiliary graft); Interval Evaluations (19–30 months, graft monitoring via imaging and ICG tests); Second Surgery (30–31 months, right liver resection); Postoperative Follow-Up (31–67 months, routine imaging and labs); End-of-Study Visit (67–70 months, final AFP measurement and imaging)