Expanding donor liver utilization: triple recipient strategy using split, domino, and auxiliary techniques

Liver transplantation (LT) faces persistent organ shortages driving innovations like split liver transplantation (SLT), domino liver transplantation (DLT) and auxiliary liver transplantation (ALT). SLT emerges as a transformative approach, enabling the transplantation of a solitary donor liver into two beneficiaries—a pediatric and an adult, an undertaking that curbs waiting list mortality rates for both demographics (1). Complementing this breakthrough, the advent of DLT permits the utilization of a liver from one transplant recipient as the donor organ for another patient, effectively facilitating the transplantation of two recipients using a “conventional” donor (2). ALT was initially used as the treatment for reversible fulminant liver failure (3). ALT has also been reported to have effective and long-term favorable results in patients with noncirrhotic metabolic liver disease and chronic cirrhotic liver disease (4,5). By amalgamating diverse transplantation methodologies, these advances serve to mitigate the organ shortage conundrum and, consequently, abate mortality on the transplant waiting list. Remarkably, we report an innovative clinical practice of LT encompassing three techniques: SLT, DLT, and ALT. These combined techniques materialize a remarkable achievement, wherein a single donor liver breathes life into three patients afflicted by end-stage liver disease, including one patient with massive liver cancer.

The donor liver was obtained from a 23-year-old female who tragically succumbed to severe head trauma. Prior to the surgery, the donor’s liver function was excellent. Following the recommendations of the surgical team, the donor liver was split into two parts: the right lobe (segments V–VIII) and the left lobe (segments II–IV) plus segment I. The middle hepatic vein was split into two halves, and iliac artery patches from the donor were used to reconstruct both grafts. According to the organ allocation policies in China, the right lobe graft was transplanted into an adult female recipient (Recipient 1, 57 years old, 54.5 kg), while the left lobe plus segment I were allocated to a young boy (Recipient 2, 13 years old, 47 kg). The right lobe (segments V–VIII) of the pediatric recipient’s liver was further allocated as an ALT for a second adult recipient (Recipient 3, 70 years old, 72.5 kg) (Figure 1A, Table 1).

Figure 1 Schematic diagram and representative preoperative imaging for the triple-recipient strategy. (A) Schematic overview of the surgical procedures. (B,C) Contrast-enhanced MRI images of Recipient 3 at initial diagnosis. (D,E) Contrast-enhanced MRI images of Recipient 3 after downstaging therapy and prior to the combined tumor resection and ALT. (F,G) Three-dimensional reconstructions based on the preoperative MRI scan of Recipient 3; the FLR (segments II and III, in white) measured 353.24 mL (18.43% of the total liver volume). ALT, auxiliary liver transplantation; FLR, future liver remnant; MRI, magnetic resonance imaging.

The procurement, graft division, and transplantation surgeries for all three recipients were successfully performed at our center. The specific treatment processes for each recipient are described as follows:

• Recipient 1 was a 57-year-old female who was admitted due to hepatitis C virus-related liver cirrhosis. The patient had a Model for End-Stage Liver Disease score of 40, and had vomited blood twice due to rupture of gastroesophageal varices caused by refractory portal hypertension syndrome. The right hepatic vein, reconstructed middle hepatic vein, right portal branch and right hepatic artery were anastomosed to the corresponding structures in the recipient. Bile duct reconstruction was performed in an end-to-end fashion with a 7-F pancreatic duct stent to prevent postoperative stricture formation.
• Recipient 2 was a 13-year-old male diagnosed with argininemia, who had a Model for End-Stage Liver Disease score of 12. The patient presented with gait abnormalities and recurrent involuntary movements for seven years. Symptomatic episodes became more frequent in the two months prior to the consultation, characterized by head tilting and stuttering that was not fully controlled with medications. The hepatic vein, portal vein branch, and hepatic artery of the left split were successively anastomosed to the corresponding vessels of the recipient. While biliary reconstruction was performed using bilio-enteric anastomosis due to the mismatch of recipient and donor bile duct dimensions. Of note, prior to implanting the donor liver graft, the surgical team performed an in vivo split of the patient’s own liver. Subsequently, the right lobe was utilized as a “domino liver graft” for the third recipient.
• Recipient 3, a 70-year-old adult male, was diagnosed with hepatocellular carcinoma (HCC) and had no prior history of cirrhosis. The contrast-enhanced magnetic resonance imaging (MRI) showed multiple lesions in the right lobe of the liver with a maximum diameter of 147 mm, accompanied by invasion of the right hepatic vein and the right posterior branch of the portal vein (Figure 1B,1C). The patient underwent 6 months of preoperative treatments, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), sorafenib immunotherapy, microwave ablation, and ligation of the right portal vein, to downstage the tumor and create a surgical opportunity. Preoperative contrast-enhanced MRI showed disappearance of the lesions in the right hepatic vein and the right posterior branch of the portal vein, and the maximum diameter of the mass was reduced to 116 mm (Figure 1D,1E). Furthermore, three-dimensional volumetry based on this MRI revealed a future liver remnant (FLR) in segments II and III of only 18.43% (353.24 mL) of the total liver volume (Figure 1F,1G). Given this objective measurement indicating a high risk of post-hepatectomy liver failure, a combined procedure of tumor resection followed by ALT was undertaken. After complete resection of the tumor, left lateral lobe of the liver was preserved. Subsequently, an auxiliary liver transplant was performed using the domino liver graft from Recipient 2. The portal vein and the hepatic artery of the domino liver graft was lengthened using the donor’s iliac vein and splenic artery, respectively. Then, the right hepatic vein, the middle hepatic vein, the right branch of the portal vein, and the right hepatic artery in the graft were anastomosed to the matching structures of the Recipient 3. The bile duct reconstruction was performed using biliary-enteric anastomosis, and because of the thin bile duct of the domino liver graft, a biliary stent was inserted, which was threaded through the abdominal wall for external bile-intestinal drainage.

The pediatric recipient developed pleural effusion due to hypoalbuminemia on postoperative day 3. After thoracocentesis drainage and administration of albumin supplementation, the pediatric recipient made a recovery. All three recipients were discharged. During the 12 months of follow-up, all three recipients remained alive with no recurrence of HCC observed in Recipient 3. Of note, Recipient 3 showed no clinical manifestations related to argininemia during the follow-up period.

All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of The Second Affiliated Hospital, Zhejiang University School of Medicine and with the Declaration of Helsinki and its subsequent amendments. Ethical approval was granted by the Ethics Committee of The Second Affiliated Hospital, Zhejiang University School of Medicine (approval No. 2023-0983). The patient provided informed consent for the publication of this article in an academic journal.

Discussion

This innovative integration of SLT, DLT, and ALT successfully addressed three distinct cases of end-stage liver disease, including a patient grappling with a large HCC. Reports on the combined application of these three techniques in a single clinical pathway have been exceedingly rare. Although Hashikura et al. previously described a two-stage domino procedure following temporary ALT in a patient with familial amyloid polyneuropathy (FAP), in which the explanted native liver was subsequently transplanted into a second recipient (6). Our approach is differentiated by its orchestrated, multi-stage design: an initial SLT was followed by an in vivo DLT from the metabolic disease recipient, culminating in an ALT for the HCC patient, thereby achieving “one donor for three recipients” through a carefully structured procedural sequence. The execution of this treatment regimen necessitates the simultaneous completion of three LT surgeries and one liver resection surgery, demanding meticulous surgical planning, excellent surgical techniques, a sufficient number of surgical personnel, and seamless teamwork. The crux of the surgical challenge lies in preserving the vascular structures of both the graft and the recipient, ensuring optimal compatibility and successful anastomosis. From an ethical perspective, this strategy was justified by its potential to save three lives with a single donor organ while providing the only curative option for the HCC patient. The favorable outcomes achieved—with all recipients surviving without recurrence or metabolic complications—affirm the ethical soundness of this approach.

This resounding success heralds a transformative breakthrough for patients confronted with prolonged waits for LT, particularly HCC patients who typically fail to meet the Milan criteria. Within our case series, the recipient presented with a large HCC, rendering complete tumor resection infeasible due to inadequate residual liver volume, a definitive surgical contraindication. In response, we adeptly harnessed the power of DLT to address this daunting challenge.

In contrast to preceding reports detailing whole LT cases, we deliberately diverged from the conventional approach of transplanting the liver of a child with argininemia into an HCC patient. Instead, we opted for ALT, deftly utilizing the right hepatic lobe of the pediatric donor. Within this framework, the remaining liver of the HCC recipient effectively compensates for the metabolic disorder inherent in the donated liver, while the donor liver seamlessly offsets the inadequate liver volume necessitated by HCC surgery. Our innovative approach effectively circumvents the potential hereditary impact of metabolic disorders on recipients.

Argininemia is a rare disorder of the urea cycle caused by arginase-1 deficiency (7). It has been reported that LT is an effective treatment for those who do not respond well to conservative treatment (8). However, there are few reports of DLT using the livers procured from patients with argininemia. Domino liver grafts are mostly obtained from patients with FAP and less common candidates are fibrinogen A α-chain amyloidosis, maple syrup urine disease (MSUD), hemochromatosis (2,9). In this article, we report a case of the patient with argininemia as a domino liver donor. The donor graft was successfully transplanted into the postoperative HCC patient during the subsequent transplantation procedure. This could provide additional experience in the use of argininemic donor livers in DLT.

Conclusions

LT is an effective and life-saving treatment for a wide range of liver disease, yet it is limited by the shortage of donor liver. Our case series represents a groundbreaking surgical strategy for the management of end-stage liver disease, successfully achieving the long-sought-after objective of “one donor for three recipients” transplantation. This significant milestone not only enriches the therapeutic armamentarium available to HCC patients but also extends the frontiers of the donor pool through judicious surgical design, thereby serving as an invaluable reference for the treatment of analogous cases in the future. In the future, different transplantation techniques should be combined more flexibly to optimize transplantation outcomes while expanding the donor liver pool.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-532/prf

Funding: This research was supported by National Natural Science Foundation of China (No. U23A20449) and Central Guidance on Local Science and Technology Development Fund of Zhejiang Province (No. 2024ZY01006).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-532/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the Ethics Committee of The Second Affiliated Hospital, Zhejiang University School of Medicine and with the Declaration of Helsinki and its subsequent amendments. Ethical approval was granted by the Ethics Committee of The Second Affiliated Hospital, Zhejiang University School of Medicine (approval No. 2023-0983). The patient provided informed consent for the publication of this article in an academic journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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