Dual, Split and Multi-Graft Liver Transplantation: Surgical Strategies to Maximize Liver Utilization

Abstract

Liver graft shortage remains a major limiting factor in contemporary liver transplantation, particularly in the setting of increasing waiting list pressure and constrained donor availability. While the biological quality of donor organs cannot be modified surgically, several operative strategies have been developed to optimize liver utilization and compensate for insufficient graft volume. These include split liver transplantation (SLT), dual-graft living donor liver transplantation (DGLT), auxiliary procedures, and selected multi-graft or hybrid configurations. This review provides an updated and structured overview of surgical concepts aimed at maximizing effective liver mass for transplantation. We discuss indications, technical considerations, and reported outcomes of split, dual, and combined graft approaches, with particular emphasis on graft-to-recipient weight ratio (GRWR), portal inflow modulation, and prevention of small-for-size syndrome. The role of machine perfusion technologies—including normothermic and hypothermic approaches—as enabling tools for graft assessment and safer utilization of partial grafts is also examined. Finally, we address ethical and logistical challenges associated with complex graft strategies and outline future directions in which advances in perfusion, graft assessment, and staged transplantation concepts may further refine patient selection and procedural safety. Collectively, these strategies represent complementary solutions for extending liver transplantation beyond conventional single-graft paradigms in highly selected settings.

1. Introduction

Liver transplantation remains the only definitive treatment for end-stage liver disease, acute liver failure, and selected metabolic disorders. Despite continuous advances in surgical technique, perioperative management, and immunosuppression, the persistent shortage of suitable liver grafts remains the principal limitation to broader access to transplantation. This imbalance is further exacerbated by an expanding waiting list, aging donor populations, and the rising prevalence of steatotic and extended-criteria donor livers. As a result, increasing numbers of candidates face prolonged waiting times or dropout due to disease progression [1,2,3].

Importantly, while surgical innovation cannot modify the intrinsic biological quality of a donor liver, it can substantially influence how available graft tissue is allocated, divided, or combined to meet recipient demands. In this context, the challenge of transplantation has progressively shifted from graft quality alone toward optimization of graft volume, hemodynamics, and utilization efficiency. Ensuring an adequate functional liver mass—expressed by the graft-to-recipient weight ratio (GRWR)—has become a central determinant of post-transplant outcomes, particularly in partial graft transplantation [4,5,6,7].

To address insufficient graft volume and reduce waiting list mortality, several surgical strategies have been developed over the past decades. Split liver transplantation (SLT) enables a single deceased donor liver to benefit two recipients and has become standard practice in pediatric transplantation, with selective application in adults. In living donor liver transplantation (LDLT), dual-graft liver transplantation (DGLT) has emerged as a solution for adult recipients in whom a single partial graft would be inadequate, allowing for adequate liver mass while limiting donor risk. In highly selected scenarios, auxiliary procedures and hybrid or multi-graft configurations—including combinations of living donor, deceased donor, or domino grafts—have been reported as rescue or resource-maximizing strategies [8,9,10,11,12].

These approaches share a common objective: prevention of small-for-size syndrome (SFSS) through sufficient graft volume, appropriate portal inflow modulation, and meticulous vascular and biliary reconstruction. Advances in perioperative management and increasing experience in high-volume centers have improved outcomes of complex graft strategies; however, these procedures remain technically demanding and raise important ethical and logistical considerations [13,14,15,16].

The aim of this review is to provide a structured overview of split, dual, and multi-graft liver transplantation strategies, focusing on their indications, technical principles, outcomes, and limitations. Emphasis is placed on factors guiding graft selection and utilization—including GRWR, portal hemodynamics, and donor safety—as well as on emerging technologies such as machine perfusion that may facilitate safer application of partial grafts. By synthesizing current evidence, this review seeks to clarify the role of complex graft strategies within modern liver transplantation practice.

2. Split Liver Transplantation

2.1. Concept and History

Split liver transplantation (SLT) is based on dividing a single deceased donor liver into two partial grafts for transplantation into two recipients. The most common configuration involves allocation of the left lateral segment (segments II–III) to a pediatric recipient and the right or extended right graft to an adult recipient. Since its introduction in the late 1980s by Pichlmayr and Bismuth, SLT has become an established strategy to expand graft availability, particularly in pediatric liver transplantation [11,12,13].

Over time, refinements in donor selection, surgical technique, and perioperative management have enabled selective application of SLT in adult recipients. However, unlike pediatric SLT, adult-to-adult splitting remains technically demanding and outcome-sensitive, largely due to higher metabolic demands and increased susceptibility to small-for-size syndrome (SFSS) [4,5,15].

2.2. Technical Approaches

SLT can be performed either in situ—with parenchymal transection in the donor prior to aortic perfusion—or ex situ, on the back table following organ retrieval. In situ splitting may reduce cold ischemia time and facilitate anatomical identification of vascular and biliary structures, whereas ex situ splitting offers logistical flexibility and remains widely used in many centers. Standardized multi-step bench splitting protocols have been reported with acceptable outcomes when performed by experienced teams [14,15,16,17].

In adult recipients, full-left/full-right split liver transplantation (FSLT) requires meticulous preoperative planning and intraoperative execution. Adequate venous outflow reconstruction—particularly involving the middle hepatic vein—portal vein branching, arterial inflow, and biliary anatomy is critical to prevent congestion, ischemia, and biliary complications. Accurate volumetric assessment and anticipation of portal hemodynamics are essential to minimize the risk of SFSS [5,15,16].

2.3. Indications and Selection

SLT is considered standard of care in pediatric liver transplantation, where the left lateral segment provides excellent size matching and outcomes comparable to whole-organ transplantation. In adult recipients, however, SLT is reserved for highly selected donor–recipient pairs. Optimal donor characteristics include young age, minimal steatosis, stable hemodynamics, and favorable vascular and biliary anatomy. Recipient selection prioritizes low portal hypertension, preserved cardiopulmonary reserve, and an anticipated graft-to-recipient weight ratio (GRWR) above accepted safety thresholds [11,15,18].

Adult recipients with severe portal hypertension, high Model for End-Stage Liver Disease (MELD) scores, or significant comorbidities are generally poor candidates for split grafts, particularly hemigrafts. In such settings, the risk of SFSS, vascular thrombosis, and biliary complications outweighs the potential benefit of increased graft utilization [5,18].

2.4. Outcomes

Outcomes of pediatric SLT are well established and largely comparable to those of whole-liver transplantation in experienced centers. In contrast, adult-to-adult FSLT has historically been associated with higher rates of early graft dysfunction, biliary complications, and inferior graft survival. Systematic reviews and registry analyses consistently demonstrate less favorable outcomes compared with whole-organ transplantation, although recent high-volume center series suggest progressive improvement with increased experience and refined selection criteria [5,13,16,19].

These findings underscore the importance of institutional expertise, standardized protocols, and careful donor–recipient matching. The learning curve effect remains a critical determinant of success, particularly in adult SLT programs [13,19].

2.5. Allocation and Policy

Allocation policies promoting an “intention-to-split” approach have significantly increased utilization of deceased donor livers for pediatric recipients. National and regional policies in Italy, the United Kingdom, and Eurotransplant prioritize pediatric access to split grafts and have been associated with reduced pediatric waiting list mortality without compromising overall transplant outcomes [20,21].

Recent EASL guidance recognizes SLT as a key strategy for expanding access to transplantation and emphasizes the need for harmonized donor selection, logistics, and center experience. Ongoing efforts focus on optimizing allocation algorithms and organ-sharing frameworks to balance equity, safety, and efficiency across transplant networks [1,20,21].

2.6. When (Not) to Perform Split Liver Transplantation?

SLT should be considered when high-quality donor organs are available, recipient selection criteria are met, and procedures are performed in experienced centers with established SLT protocols. Conversely, SLT is generally discouraged in the presence of poor donor quality, unfavorable anatomy, severe recipient portal hypertension, or limited institutional experience. Under such circumstances, alternative strategies—including whole-organ transplantation or combined graft approaches—may offer superior risk–benefit profiles [5,15,18].

3. Dual-Graft Liver Transplantation (DGLT)

3.1. Concept and Rationale

Dual-graft liver transplantation (DGLT) is a surgical strategy in which two partial liver grafts are implanted into a single recipient to achieve sufficient functional liver mass when a single graft would be inadequate. The concept was first introduced in the early 2000s in the setting of adult living donor liver transplantation, most notably through the use of dual left-lobe grafts, and was driven by the need to balance recipient safety with donor risk minimization [22,23,24].

The primary rationale for DGLT lies in overcoming insufficient graft volume while avoiding the elevated donor morbidity associated with right-lobe donation. In adult recipients with high metabolic demand or unfavorable size matching, a single left-lobe or left-lateral graft may result in an unacceptably low graft-to-recipient weight ratio (GRWR), increasing the risk of small-for-size syndrome (SFSS). By combining two smaller grafts—most commonly left-lobe or left-lateral grafts—from two donors, DGLT allows for the attainment of an adequate cumulative graft volume while preserving a lower-risk donation profile for each individual donor [22,25,26,27].

Beyond graft volume, portal hemodynamics represent a central consideration in the rationale for DGLT. Partial grafts are particularly vulnerable to excessive portal inflow, leading to sinusoidal injury, cholestasis, and impaired regeneration. Distributing portal inflow across two grafts reduces per-graft portal flow and shear stress, thereby mitigating the risk of small-for-flow injury. This hemodynamic advantage complements volumetric adequacy and distinguishes DGLT from single-graft partial transplantation [7,28,29].

DGLT should not be viewed as a routine alternative to standard living donor or deceased donor liver transplantation. Rather, it represents a highly selective solution for scenarios in which a timely whole-organ graft is unavailable and a single partial graft would be insufficient or unsafe. Its application is therefore closely tied to center experience, donor availability, and the ability to coordinate complex multi-team procedures while maintaining rigorous donor safety standards [23,24,30].

3.2. Indications and Selection

Dual-graft liver transplantation is primarily indicated in adult recipients for whom a single partial graft would not provide sufficient functional liver mass, while a right-lobe donation would expose the donor to disproportionate risk. Typical clinical scenarios include recipients with a large body size, high metabolic demand, or unfavorable donor–recipient size mismatch, in whom the anticipated graft-to-recipient weight ratio (GRWR) of a single left-lobe or left-lateral graft would fall below accepted safety thresholds [22,25,27].

Recipient selection for DGLT focuses on minimizing the risk of small-for-size and small-for-flow syndromes through combined volumetric and hemodynamic assessment. Candidates often exhibit moderate to advanced portal hypertension but remain physiologically stable enough to tolerate prolonged operative time and complex reconstruction. Preoperative evaluation should include detailed volumetry, assessment of portal vein diameter and flow, and careful exclusion of severe cardiopulmonary comorbidities that would compromise postoperative recovery [7,28,29].

From a donor perspective, DGLT is most commonly pursued when two suitable low-risk donors are available for left-lobe or left-lateral segment donation. This approach preserves donor safety by avoiding right-lobe hepatectomy, which carries higher morbidity and mortality rates. Donor selection must adhere to strict criteria, including favorable anatomy, the absence of steatosis, and independent informed consent free of coercion, particularly given the involvement of two donors for a single recipient [27,31,32,33].

Conversely, DGLT is generally contraindicated in recipients with severe portal hypertension refractory to modulation, advanced systemic illness, or an urgent need for rapid transplantation when coordination of two donor procedures would cause unacceptable delay. In such cases, alternative strategies—such as whole-organ deceased donor transplantation or, in selected settings, auxiliary or staged approaches—may provide a more appropriate balance of risk and benefit [22,28,30].

Overall, DGLT represents a highly selective solution situated between standard single-graft transplantation and experimental multi-stage approaches. Its successful application depends on rigorous recipient selection, meticulous donor evaluation, and the availability of experienced multidisciplinary teams capable of managing the increased technical and logistical complexity inherent to dual-graft procedures [23,24].

3.3. Operation Strategy and Technical Challenges

Dual-graft liver transplantation requires meticulous preoperative planning and precise intraoperative coordination, as two independent grafts must be implanted with separate vascular inflow, venous outflow, and biliary reconstructions. The procedure is typically performed using parallel surgical teams to minimize operative time and ischemia, underscoring the need for substantial institutional resources and experience [23,24].

Graft positioning and orientation represent a central technical challenge. When a left-lobe or left-lateral segment is used as the second graft, it is frequently rotated by 180 degrees and implanted heterotopically, most commonly in the right upper quadrant. This orientation facilitates alignment of the portal vein, hepatic artery, and biliary structures while allowing for adequate venous outflow reconstruction, often via direct anastomosis to the inferior vena cava or hepatic vein confluence. Such modifications, however, increase technical complexity and require careful attention to avoid kinking, torsion, or tension on vascular and biliary anastomoses [28,29,30,34].

Each graft in DGLT necessitates independent portal venous inflow, hepatic arterial inflow, and venous outflow. Venous drainage is particularly critical, as inadequate outflow can result in graft congestion, impaired regeneration, and early graft dysfunction. Reconstruction strategies may involve direct hepatic vein anastomoses, venous graft interposition, or creation of a common outflow channel, depending on graft anatomy and orientation. Biliary reconstruction is similarly demanding, with separate biliary anastomoses increasing the risk of leaks and strictures [23,30,34].

Portal inflow modulation is frequently employed as an adjunct to prevent small-for-flow injury, even when cumulative graft volume appears sufficient. Techniques such as splenic artery ligation, splenectomy, or splenic artery embolization may be used to reduce portal pressure and distribute flow more evenly between grafts. Intraoperative assessment of portal pressures and flows can guide the need for and extent of modulation, emphasizing the dynamic nature of hemodynamic management in DGLT [28,29].

Collectively, these technical demands translate into longer operative times and higher procedural complexity compared with single-graft transplantation. Consequently, DGLT should be confined to centers with established expertise in living donor liver transplantation, access to multidisciplinary teams, and the capacity for intensive postoperative monitoring. In such settings, careful execution of operative strategy can mitigate risks and allow DGLT to achieve outcomes comparable to conventional approaches in selected patients [23,24].

3.4. Outcomes

Reported outcomes of dual-graft liver transplantation largely originate from high-volume living donor liver transplantation centers and reflect careful recipient selection and accumulated institutional experience. The largest single-center series to date, comprising approximately 400 adult DGLT procedures, demonstrated 1-, 5-, and 10-year patient survival rates of 89%, 85%, and 80%, respectively. These outcomes were comparable to matched cohorts undergoing single-graft adult living donor liver transplantation, despite significantly longer operative times and increased technical complexity [23,24,35].

While overall survival appears acceptable, DGLT is consistently associated with higher rates of surgical complications compared with single-graft transplantation. These include biliary complications, vascular thrombosis, and postoperative infections, reflecting the need for multiple anastomoses and prolonged operative duration. Importantly, complication rates are generally reported on a per-patient basis rather than per-graft, emphasizing the cumulative procedural burden inherent to dual-graft approaches [23,24,30].

Early graft dysfunction and small-for-size or small-for-flow syndromes are uncommon when adequate cumulative graft volume is achieved and portal inflow is appropriately modulated. This highlights the central role of hemodynamic management in determining outcomes, often outweighing volumetric considerations alone. Centers reporting favorable results uniformly emphasize strict preoperative planning, intraoperative portal pressure monitoring, and readiness to perform inflow modulation when indicated [7,28,29].

Smaller series and case reports from additional centers corroborate the feasibility of DGLT but also underline its sensitivity to center experience. Programs with limited exposure to complex living donor transplantation have reported higher complication rates and variable outcomes, reinforcing the notion that DGLT should remain confined to specialized, high-volume centers [24,26,30].

In summary, DGLT can achieve long-term survival comparable to conventional living donor liver transplantation in carefully selected recipients, albeit at the cost of increased surgical complexity and perioperative morbidity. These outcomes support its role as a selective strategy for addressing graft size mismatch rather than a broadly applicable alternative to standard transplantation [23,24,35].

3.5. Donor Safety and Ethical Considerations

Donor safety represents the central ethical concern in living donor liver transplantation and is further amplified in dual-graft liver transplantation, where two donors are exposed to operative risk for the benefit of a single recipient. The ethical acceptability of DGLT is therefore fundamentally linked to rigorous risk minimization for each individual donor [31,32,33].

Available data consistently demonstrate that left-lobe and left-lateral segment donations are associated with substantially lower morbidity and mortality compared with right-lobe hepatectomy. Reported donor mortality for left-sided donations is approximately 0.1%, whereas right-lobe donation carries a higher estimated mortality of 0.4–0.5%, alongside increased postoperative morbidity. Within this context, DGLT using two left-sided grafts may confer a lower cumulative donor risk than a single right-lobe donation, while still achieving adequate graft volume for the recipient [31,32,33].

Beyond quantitative risk assessment, ethical practice in DGLT requires robust informed consent processes and protection of donor autonomy. Given the involvement of two donors, particular attention must be paid to the potential for familial or social pressure, implicit coercion, or unequal risk perception. Comprehensive donor evaluation should include independent medical and psychological assessment, repeated consent discussions, and clear communication of both common and rare complications, including the possibility of severe morbidity or death [32,33].

From an ethical standpoint, DGLT is generally justified only when a timely whole-organ graft is unavailable and when alternative single-donor strategies would expose donors to higher individual risk. Most centers therefore restrict DGLT to highly selected cases managed within established living donor programs, supported by multidisciplinary teams and institutional oversight mechanisms. Transparent reporting of outcomes and ongoing audit are essential to ensure continued ethical justification of this approach [31,32,33,36].

In summary, donor safety considerations do not preclude the use of DGLT but impose strict conditions on its application. When performed within carefully defined ethical and clinical boundaries, DGLT represents a rational extension of living donor liver transplantation aimed at balancing recipient benefit against minimized donor risk.

3.6. Hybrid Configuration

Beyond conventional dual-graft living donor liver transplantation using two living donors, several hybrid dual-graft configurations have been reported in highly selected clinical scenarios. These approaches combine grafts from different sources to achieve adequate functional liver mass when standard options are unavailable or contraindicated [36,37].

One reported strategy involves pairing a living donor graft with a partial graft that would otherwise be discarded, such as a liver segment resected during surgery for a benign hepatic tumor. In urgent settings, this “waste-to-graft” concept has been used to augment graft volume and rescue recipients with insufficient liver mass, while avoiding additional donor morbidity [36].

Another hybrid configuration combines a living donor partial graft with a domino whole-liver graft obtained from a recipient undergoing transplantation for a metabolic disorder. In such cases, the domino graft provides baseline liver function, while the living donor graft supplements total volume and reduces the risk of small-for-size or small-for-flow syndromes. Although conceptually related to dual-graft transplantation, this approach occupies a transitional space between conventional DGLT and multi-graft or auxiliary strategies [37].

Despite their conceptual appeal, hybrid dual-graft configurations remain exceptional procedures. They are associated with increased technical complexity, logistical challenges, and unresolved ethical considerations regarding graft allocation and donor consent. Consequently, these strategies should be regarded as rescue or resource-maximizing options reserved for experienced centers and exceptional circumstances, rather than as standardized alternatives to established dual-graft or whole-organ transplantation [36,37].

4. Experimental “Triple” Approaches

4.1. Auxiliary Partial Orthotopic Liver Transplantation (APOLT)

Auxiliary partial orthotopic liver transplantation (APOLT) is a strategy in which a partial donor graft is implanted while a portion of the recipient’s native liver is preserved. The retained native liver contributes to early postoperative liver function and may undergo gradual replacement by the transplanted graft through regenerative processes. Historically, APOLT has been applied primarily in acute liver failure and selected metabolic disorders, where preservation of native liver tissue offers potential functional or metabolic advantages [38,39].

In the context of chronic liver disease and insufficient graft volume, APOLT has been explored as a means to mitigate small-for-size syndrome by sharing functional demand between the auxiliary graft and the native liver remnant. A recent systematic review reported that APOLT can achieve acceptable long-term survival in carefully selected patients; however, these outcomes are accompanied by high rates of postoperative morbidity and significant technical complexity. Critical challenges include balanced portal inflow distribution between the graft and native liver, reliable venous outflow reconstruction, and strict oncologic surveillance when the native liver is cirrhotic [38,39].

Technical execution of APOLT requires precise volumetric planning and intraoperative flow modulation to prevent competitive portal flow, which may impair graft regeneration or precipitate native liver hyperperfusion. Various strategies—including selective portal vein ligation or embolization—have been employed to favor graft hypertrophy while maintaining sufficient overall liver function during the early postoperative period. These demands contribute to prolonged operative times and increased perioperative risk [38].

Given these limitations, APOLT should not be considered a routine alternative to standard transplantation or dual-graft strategies. Its use is generally confined to highly specialized centers and exceptional clinical circumstances, such as when a whole-organ graft is unavailable and no single or dual partial graft can safely provide adequate liver mass. In such settings, APOLT represents a salvage or bridge strategy rather than a definitive solution [38,39].

4.2. Hybrid Dual-Graft Concepts (Combining Sources)

In situations where a second living donor is unavailable or unsuitable, hybrid dual-graft strategies combining grafts from different sources have been reported as exceptional solutions to achieve adequate functional liver mass. These approaches seek to maximize utilization of available hepatic tissue while minimizing additional donor risk, but remain limited to highly selected cases and experienced centers [40,41].

One such strategy involves combining a living donor partial graft with a graft segment that would otherwise be discarded, such as a liver segment resected during surgery for a benign hepatic lesion. In urgent or high-acuity settings, this “salvage utilization” approach has been used to augment graft volume and prevent small-for-size syndrome, effectively transforming surgical waste into a life-saving resource. However, variability in graft quality, ischemia exposure, and biliary anatomy introduces substantial technical and functional uncertainty [40].

Another reported hybrid concept pairs a living donor graft with a deceased donor graft that does not meet criteria for standalone transplantation but can contribute meaningful functional mass when combined. Such configurations require careful assessment of graft viability and compatibility, as well as complex logistical coordination to synchronize procurement, implantation, and postoperative management [41].

Despite their innovative nature, hybrid dual-graft approaches are associated with significant technical, ethical, and regulatory challenges. Allocation fairness, consent processes, and outcome predictability remain unresolved issues, limiting their broader applicability. Accordingly, these strategies should be regarded as rescue solutions employed only when conventional single- or dual-graft options are unavailable and when the anticipated benefit outweighs the cumulative procedural risk [40,41].

4.3. Domino Transplantation Combined with Living Donor Grafts

Domino liver transplantation involves reuse of an explanted liver from a transplant recipient with a metabolic disorder, where the liver is structurally and functionally intact but carries a specific enzymatic defect. Traditionally, domino grafts have been transplanted as whole organs into carefully selected recipients, expanding the donor pool while accepting delayed metabolic risk [42,43].

In selected cases, domino grafts have been combined with a partial living donor graft to augment functional liver mass and reduce the risk of small-for-size or small-for-flow syndromes. In this configuration, the domino graft provides baseline hepatic function, while the living donor graft supplements overall volume and regenerative capacity. Although technically representing a dual-graft procedure, this approach is conceptually aligned with multi-graft strategies due to the combination of grafts with distinct biological and functional profiles [42].

Reported experience with domino-plus-living-donor transplantation is limited to isolated case reports and small series. These reports demonstrate technical feasibility but also highlight considerable uncertainty regarding long-term outcomes, particularly concerning metabolic disease transmission, graft interaction, and cumulative procedural risk. Careful recipient selection and extensive preoperative counseling are therefore essential [42,43].

Given these uncertainties, domino graft combinations should be regarded as rescue strategies rather than reproducible solutions. Their application should be restricted to highly specialized centers with experience in both domino and living donor liver transplantation, robust ethical oversight, and the ability to provide long-term metabolic surveillance [42,43].

4.4. Domino Pathways and Allocation Strategy

Beyond individual hybrid cases, renewed interest in domino liver transplantation has prompted discussion on broader allocation pathways aimed at maximizing utilization of structurally functional grafts that would otherwise remain underused. In carefully selected metabolic disorders, domino grafts can extend the donor pool while maintaining acceptable recipient outcomes, provided that disease transmission risks are well characterized and matched to recipient profiles [43,44].

Recent reports emphasize the importance of structured allocation frameworks when considering domino or hybrid graft strategies. Clear criteria regarding donor disease type, recipient life expectancy, and acceptable metabolic risk are essential to ensure ethical consistency and transparency. In some programs, domino grafts are preferentially allocated to older recipients or those with limited alternatives, thereby balancing long-term metabolic risk against immediate survival benefit [43].

When domino grafts are incorporated into multi-graft or hybrid configurations, allocation complexity increases further. These cases often require coordination across transplant networks, individualized ethical review, and deviation from standard allocation algorithms. As such, their use highlights the tension between individualized life-saving decisions and equitable organ distribution at the population level [44].

Current European guidance frameworks, including those from EASL and the EDQM, acknowledge domino transplantation as a legitimate but highly selective strategy and emphasize the need for outcome reporting, registry inclusion, and continuous audit. Within this context, domino-based pathways should be regarded as complementary tools rather than scalable solutions to organ shortage, reinforcing the principle that exceptional graft strategies demand exceptional oversight [43,44].

4.5. Take Home Message

Experimental and hybrid multi-graft strategies represent the outer limits of contemporary liver transplantation. Approaches such as auxiliary partial orthotopic liver transplantation, hybrid dual-graft configurations, and domino-based combinations have demonstrated technical feasibility in carefully selected cases, primarily as rescue solutions when standard graft options are unavailable.

However, these strategies are consistently associated with increased technical complexity, higher perioperative morbidity, and unresolved ethical and logistical challenges. Their success depends not only on surgical expertise but also on meticulous patient selection, advanced hemodynamic control, and comprehensive institutional oversight.

Consequently, multi-graft and “near-triple” transplantation concepts should not be viewed as scalable solutions to organ shortage. Instead, they should be reserved for exceptional circumstances within high-volume centers, where outcomes can be closely monitored and reported. Within these boundaries, experimental graft strategies may serve as valuable extensions of existing transplantation paradigms rather than replacements for established practice.

A concise comparison of the main surgical strategies discussed in Section 2, Section 3 and Section 4 is provided in

Table 1. Overview of surgical strategies to increase liver graft utilization and their main advantages and limitations.

Approach	Typical Indication/Goal	Key Technical Considerations	Main Advantages	Main Limitations/Risks
Split liver transplantation (SLT; deceased donor)	Increase utilization by dividing one donor liver to serve two recipients (often pediatric + adult, or two adults in selected cases).	Donor quality and anatomy; allocation logistics; precise vascular/biliary division; ischemia time control; recipient matching (size/GRWR).	Expands the donor pool; can benefit small recipients and reduce waiting list mortality; uses one donor to help two patients.	Higher technical complexity; increased biliary/vascular complications; requires experienced center and coordination; risk that issues in one graft affect outcomes for both recipients.
Dual-graft living donor liver transplantation (DGLT)	Provide adequate functional liver mass for an adult recipient when a single partial graft would be small-for-size.	Two donors; combined GRWR target; venous outflow reconstruction; portal inflow modulation to prevent hyperperfusion; meticulous donor safety assessment.	Adequate graft volume with smaller donor hepatectomies; mitigates small-for-size risk; increases feasibility for large recipients.	Two donors exposed to risk; longer operative time and complexity; higher resource use; complex inflow/outflow management and biliary reconstruction.
Hybrid dual-graft approaches (living + deceased donor/split combinations)	Bridge mismatch between available graft(s) and recipient needs when a single graft is marginal in size or quality.	Coordination of procurement and timing; tailored reconstruction (multiple inflow/outflow anastomoses); careful hemodynamic management.	Adds flexibility to overcome graft-size or quality constraints; can reduce dependence on a single marginal graft.	Logistically challenging; very center-dependent; higher operative complexity and complication burden.
Triple-graft/multi-graft (“near-triple”) transplantation	Extreme graft/recipient size mismatch or limited graft availability where two grafts are still insufficient.	Multiple graft implantation and reconstruction; prolonged operative and ischemia times; complex biliary/vascular planning; intensive perioperative monitoring.	Potentially life-saving option in exceptional cases; maximizes use of available partial grafts.	Highly complex and resource-intensive; increased risk of thrombosis, biliary complications, and infections; limited evidence and narrow applicability.
Auxiliary partial orthotopic liver transplantation (APOLT)	Provide temporary/supportive liver function while retaining the native liver (e.g., acute liver failure) or treat selected metabolic disorders.	Portal flow competition; graft positioning and outflow; possible native liver regeneration; immunosuppression strategy and follow-up.	Native liver recovery may allow for reduction/withdrawal of immunosuppression; smaller graft may suffice; preserves native liver function.	Technical complexity; risk of graft atrophy from low portal flow; thrombosis/biliary complications; strict patient selection needed.
Domino transplantation (including combinations with partial graft strategies)	Reuse an explanted liver from a donor with a metabolic disorder for a suitable recipient to expand graft availability.	Recipient selection and counseling; disease transmission risk; logistics of sequential transplantation; long-term follow-up.	Increases the number of usable grafts; can shorten waiting time for selected recipients.	Risk of transmitting donor metabolic disease; limited indications; ethical/consent considerations and long-term surveillance required.

.

5. Ethical and Logistical Concerns

5.1. Donor Risk (Two Donors, One Recipient)

Living-donor liver transplantation inherently involves exposing healthy individuals to surgical risk for the benefit of another person. In the context of dual- and multi-graft strategies, ethical justification relies on the principle of proportionality, whereby cumulative donor risk must remain acceptable relative to anticipated recipient benefit. Current evidence supports the preferential use of lower-risk left-sided grafts when multiple donors are involved, as this approach may result in equal or lower overall donor risk compared with a single right-lobe donation [31,32,33].

Accordingly, dual- or multi-graft transplantation should only be considered when donor risk can be minimized and when alternative single-graft strategies are either unavailable or associated with greater individual donor morbidity. These considerations place donor safety at the forefront of decision-making and underscore the need for strict institutional safeguards [31,32,33,36].

5.2. Informed Consent and Donor Autonomy

Robust informed consent is essential in all forms of living donor transplantation and assumes heightened importance when more than one donor is involved. Donors must be fully informed of both common and rare complications, including the possibility of severe morbidity or death, and must retain the freedom to withdraw consent at any stage without consequence. Independent donor advocacy, psychological assessment, and repeated consent discussions are widely regarded as best practice [32,33].

Particular attention should be paid to mitigating implicit coercion arising from familial or social dynamics, especially in dual-donor scenarios. Ensuring donor autonomy is a prerequisite for ethical acceptability and cannot be substituted by procedural success or recipient urgency [32].

5.3. Center Experience, Resources and Operative Burden

Dual-graft and auxiliary transplantation strategies impose substantial logistical demands on transplant programs. These procedures often require multiple operating rooms, parallel surgical teams, extended operative times, and advanced postoperative critical care. Consequently, outcomes are strongly influenced by institutional experience and resource availability [23,24,45].

Most authors and guideline bodies recommend restricting complex graft strategies to high-volume centers with established living donor programs and demonstrated expertise in vascular and biliary reconstruction. Centralization of such procedures may improve outcomes while preserving donor safety and efficient use of healthcare resources [36,45].

5.4. Allocation Fairness and Regulatory Frameworks

The application of split, dual, and hybrid graft strategies raises important questions regarding allocation fairness and transparency. While split liver transplantation is supported by structured national and regional policies—particularly for pediatric recipients—dual and multi-graft approaches often fall outside standard allocation algorithms and require individualized ethical review [1,37,38,46,47].

European guidance from organizations such as EASL and the EDQM emphasizes the need for transparent selection criteria, prospective outcome reporting, and continuous audit when employing non-standard graft strategies. Adherence to these frameworks is essential to balancing individualized life-saving decisions against equitable organ distribution at the population level [1,38].

5.5. When (Not) to Apply Complex Graft Strategies?

Across published experience and guideline recommendations, consensus converges on a limited set of conditions under which dual, auxiliary, or multi-graft transplantation may be ethically and clinically justified. These strategies should be considered only when (1) a timely whole-organ graft is unavailable, (2) donor risk can be minimized, and (3) the procedure is performed in a specialized, high-volume center with appropriate expertise and infrastructure [1,38,45].

Conversely, complex graft strategies should be avoided in settings characterized by poor donor quality, excessive recipient risk, limited institutional experience, or inability to provide comprehensive postoperative monitoring. Within these constraints, selective application of advanced graft strategies can complement—but not replace—conventional liver transplantation pathways.

6. Prospects

6.1. Liver Machine Perfusion as an Enabling Technology

Liver machine perfusion (LMP) is increasingly recognized not only as an advanced preservation modality, but also as an enabling technology that facilitates safer utilization of partial, extended-criteria, and technically complex grafts. By allowing for dynamic preservation, real-time viability assessment, and mitigation of ischemia–reperfusion injury, LMP addresses several limitations of static cold storage, particularly in grafts with limited functional reserve [39,40,41,42].

Clinical and experimental evidence accumulated over the past decade demonstrates that hypothermic oxygenated perfusion (HOPE/D-HOPE), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP) improve early graft function, reduce ischemic cholangiopathy, and increase utilization rates of donation-after-circulatory-death and extended-criteria grafts. These effects may be relevant in split, dual-graft, and auxiliary transplantation, where graft volume, microcirculatory stability, and biliary integrity critically influence outcomes [39,40,41,42,48,49].

Beyond preservation, LMP enables objective pre-implantation viability assessment. Parameters such as lactate clearance, bile production and composition, perfusion hemodynamics, and markers of hepatocellular and mitochondrial injury are increasingly incorporated into clinical decision-making algorithms. This capability is particularly valuable when considering complex graft strategies, as it allows for the exclusion of grafts with insufficient functional reserve before exposing recipients and donors to additional procedural risk [43,44,50,51].

Recent comprehensive analyses highlight the transition of LMP from an experimental technique toward routine application in high-risk graft scenarios, while also emphasizing unresolved issues related to protocol standardization, cost-effectiveness, and long-term outcome validation. In this context, LMP should be regarded as a complementary technology that enhances graft assessment and utilization rather than as a standalone solution to organ shortage [45,52,53,54,55].

Importantly, integration of LMP into complex graft strategies does not obviate the need for strict recipient selection, meticulous hemodynamic control, and institutional expertise. Instead, LMP provides an additional layer of safety and decision support, enabling transplant teams to extend graft utilization within controlled and ethically sound limits [56].

For clarity, the main machine perfusion modalities and their potential roles in split/dual-graft and auxiliary settings are summarized in

Table 2. Overview of machine perfusion modalities and potential applications relevant to split, dual-graft, and auxiliary liver transplantation.

Modality	Typical Temperature/Setting	Primary Goals	Practical Advantages	Potential Limitations/Considerations
Hypothermic oxygenated perfusion (HOPE/D-HOPE)	Hypothermic ex situ perfusion with oxygenation (often via portal ± arterial inflow).	Mitochondrial resuscitation; reduction in ischemia–reperfusion injury; improved microcirculation and biliary protection.	Relatively simple add-on to cold preservation; may improve graft quality before implantation; fits time-critical logistics.	Device availability; protocol heterogeneity; effect size may vary by donor type and injury severity; still requires careful recipient matching.
Normothermic machine perfusion (NMP; ex situ)	Physiological temperature ex situ perfusion with oxygenated blood-based or acellular perfusate.	Real-time functional assessment (e.g., lactate clearance, bile production/composition); active repair and resuscitation.	Enables viability testing and potential reconditioning; may reduce discard rates; may allow for better planning for complex reconstructions.	More resource-intensive; requires expertise and monitoring; longer preparation time; standardized viability thresholds still evolving.
Normothermic regional perfusion (NRP; in situ, typically DCD)	Restoration of oxygenated circulation in the donor region prior to organ retrieval.	Reversal of warm ischemic injury; improved organ quality from DCD donors; potential reduction in biliary complications.	Uses the donor as the “circuit”; may improve DCD graft outcomes; can increase usable grafts for high-demand recipients.	Ethical/legal constraints by jurisdiction; logistic complexity; requires trained procurement teams; not applicable to all donor types.
Static cold storage (SCS; baseline comparator)	Conventional cold preservation on ice.	Slow metabolism; transport and logistical simplicity.	Widely available; inexpensive; compatible with most procurement pathways.	Limited ability to assess or repair grafts; may be suboptimal for marginal grafts or complex multi-graft strategies.

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6.2. From Extended-Criteria to Transplantable: Assessment, Repair, and Regenerative Strategies

Advances in liver machine perfusion have shifted graft evaluation from static donor-based criteria toward dynamic functional assessment. Rather than classifying grafts solely according to donor characteristics, contemporary strategies increasingly emphasize functional performance during perfusion, enabling real-time decision-making regarding graft utilization prior to implantation [43,44,50].

During normothermic and hypothermic perfusion, targeted interventions aimed at graft optimization—such as modulation of ischemia–reperfusion injury, inflammatory pathways, and metabolic support—have been explored, particularly in steatotic and extended-criteria grafts. While early clinical experience suggests potential benefits, the reproducibility and durability of these effects remain variable [39,40,41,42,43].

The integration of biochemical, hemodynamic, and biliary parameters into structured viability assessment frameworks represents a critical step toward standardized utilization of higher-risk grafts. Consensus documents emphasize that such tools should complement, rather than replace, established clinical judgment and selection criteria [43,44,50].

At present, graft optimization strategies should be regarded as adjunctive measures that refine risk stratification and expand utilization within controlled limits, rather than as technologies that fundamentally transform graft quality. Further progress will depend on harmonization of perfusion protocols, multicenter validation, and incorporation into existing allocation frameworks [43,44,50,51,52].

6.3. Staged Transplantation and RAPID Concepts

Staged transplantation strategies have emerged as an alternative approach to address insufficient graft volume in selected recipients, aiming to bridge the gap between partial graft transplantation and whole-organ replacement. Among these, the resection and partial liver transplantation with delayed hepatectomy (RAPID) concept represents the most structured and extensively discussed model [44,50,51,52].

The RAPID approach involves implantation of a partial liver graft—most commonly segments II and III—followed by a period of graft hypertrophy under controlled portal inflow, after which the diseased native liver is removed in a second-stage hepatectomy. This staged strategy seeks to mitigate small-for-size syndrome by temporally separating graft implantation from full metabolic demand [44,50,51].

Early clinical experience and feasibility studies suggest that RAPID may allow for transplantation in patients who would otherwise be unsuitable for partial grafts alone. However, reported series remain limited, and the approach is associated with significant technical complexity, prolonged treatment course, and substantial perioperative risk. Careful patient selection, precise portal flow modulation, and close postoperative monitoring are critical determinants of success [44,50,51,52].

At present, RAPID should be regarded as a highly selective strategy rather than a broadly applicable solution to graft shortage. Its role appears confined to specialized centers and carefully chosen clinical scenarios, complementing—but not replacing—established split and dual-graft transplantation strategies. Further evaluation through structured clinical programs and registries is required before wider adoption can be considered [44,50,51,52].

6.4. Cell-Based (Hepatocyte) Therapy as Bridging Strategies

Cell-based therapies, particularly hepatocyte transplantation, have been explored as a potential bridge to liver transplantation or as temporary support in selected metabolic disorders and acute liver failure. The conceptual appeal lies in providing partial hepatic function without the need for whole-organ replacement, thereby stabilizing patients until definitive transplantation becomes feasible [53].

Clinical experience to date suggests that hepatocyte transplantation has a favorable short-term safety profile; however, durable clinical efficacy remains inconsistent. Limitations include poor long-term cell engraftment, loss of function over time, and lack of standardized protocols for cell sourcing, dosing, and delivery. Consequently, hepatocyte therapy has not achieved widespread adoption as a standalone treatment [53].

Within the context of graft-shortage mitigation, cell-based approaches may serve as adjunctive or bridging strategies rather than definitive alternatives to transplantation. Their potential role lies in temporizing liver dysfunction in carefully selected patients, complementing—but not replacing—surgical graft-based solutions [53].

6.5. Xenotransplantation and Extracorporeal Liver Support

Recent advances in genetic engineering have renewed interest in xenotransplantation as a form of temporary liver support. Experimental models using gene-edited porcine livers have demonstrated short-term metabolic and synthetic function, both in extracorporeal perfusion systems and in highly controlled in situ settings. These approaches are conceptually positioned as bridge therapies rather than permanent graft solutions [45,54,55]

Early human feasibility studies and regulatory-approved clinical trials have focused on extracorporeal porcine liver perfusion as a dialysis-like support for critically ill patients with acute liver failure. While these studies demonstrate proof of concept, they also highlight substantial challenges related to immunologic compatibility, coagulation disturbances, infection risk, and ethical oversight [45,54,55].

At present, xenogeneic liver support remains firmly within the experimental domain. Its relevance to graft utilization lies primarily in its potential role as a temporary stabilizing measure, buying time for recovery or allocation of a suitable human graft. As such, xenotransplantation should be viewed as a complementary investigational strategy rather than a near-term solution to organ shortage [45,54,55].

7. Conclusions

Persistent graft shortage remains the defining limitation of contemporary liver transplantation, progressively shifting clinical focus from donor availability alone toward strategies that optimize effective liver utilization. Within this framework, split liver transplantation has become an established and policy-supported solution for expanding access—particularly in pediatric recipients—while dual-graft living donor transplantation offers a selective yet validated approach for adult recipients in whom a single partial graft would be insufficient and donor risk can be proportionally minimized.

Beyond these established strategies, experimental and hybrid approaches—including auxiliary transplantation and multi-graft configurations—demonstrate that further extension of graft utilization is technically feasible but accompanied by substantial operative complexity, higher morbidity, and unresolved ethical and logistical challenges. As such, these techniques should remain confined to exceptional circumstances and centers with advanced expertise, rather than be considered scalable solutions to organ shortage.

Concurrently, advances in machine perfusion, standardized viability assessment, and staged transplantation concepts have emerged as important enabling technologies that refine decision-making in complex graft scenarios. By improving graft assessment, supporting safer utilization of partial and extended-criteria grafts, and reducing uncertainty in high-risk situations, these innovations complement—but do not replace—careful recipient selection, hemodynamic control, and institutional experience.

Ultimately, dual, split, and multi-graft strategies represent a continuum of increasingly complex solutions aimed at balancing recipient benefit, donor safety, and allocation fairness. Their appropriate integration into modern liver transplantation practice will depend on rigorous selection criteria, transparent governance, and continuous outcome evaluation, ensuring that surgical innovation remains aligned with ethical responsibility and durable clinical benefit.