Minireviews Open Access
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Sep 18, 2025; 15(3): 103015
Published online Sep 18, 2025. doi: 10.5500/wjt.v15.i3.103015
Impact of donor obesity on paediatric liver transplantation; current evidence and potentials for graft pool expansion
Amr Alnagar, Department of General Surgery, University Hospitals of Birmingham, Birmingham B13 0QB, United Kingdom
Ahmed Amgad, Faculty of Medicine, Helwan University, Cairo 4034572, Al Qāhirah, Egypt
Tassos Grammatikopoulos, Department of Paediatric Liver, GI and Nutrition, King's College Hospital, London SE5 9RS, United Kingdom
Eirini Kyrana, Roger Williams Institute of Liver Studies, King's College London, London SE5 9NT, United Kingdom
ORCID number: Amr Alnagar (0000-0003-3434-6459); Ahmed Amgad (0000-0002-7907-1471); Tassos Grammatikopoulos (0000-0002-0174-4787); Eirini Kyrana (0000-0002-4696-4855).
Co-first authors: Amr Alnagar and Ahmed Amgad.
Author contributions: Alnagar A and Amgad A designed the study, conducted the literature review, and wrote the manuscript draft; they contribute equally to this study as co-first authors; Grammatikopoulos T and Kyrana E performed the critical revision and final drafting of the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare that are relevant to the content of this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Amr Alnagar, PhD, Department of General Surgery, University Hospitals of Birmingham, 6 Chamberlain Road, Birmingham B13 0QB, United Kingdom. amr.alnagar@nhs.net
Received: November 5, 2024
Revised: March 12, 2025
Accepted: March 26, 2025
Published online: September 18, 2025
Processing time: 164 Days and 12.2 Hours

Abstract

Paediatric liver transplantation (PLT) is a life-saving procedure for children with advanced liver disease or hepatoblastoma. The number of available grafts is limited in relation to the number of children on PLT waiting list. This graft shortage has led transplant societies and healthcare organizations to explore ways to investigate possible options and expand the donor pool. The safe use of grafts from obese donors has always been a subject of debate among PLT specialists. Donors’ obesity is strongly associated with hepatic steatosis which can affect graft function by impairing microcirculation and maximizing the potential of ischemia-reperfusion injury. Donor body mass index consideration should go hand in hand with the workup for hepatic steatosis which is an independent predictor for early graft dysfunction. New strategies to optimize the grafts before PLT such as normothermic regional perfusion and ex vivo liver perfusion can potentially mitigate the risk of using grafts from obese donors. This review summarizes the available evidence about the impact of donor obesity on PLT and highlights the current policies to widen the graft pool and suggest future research directions to improve donor selection and patient outcomes.

Key Words: Paediatric liver transplantation; Obesity; Graft pool; Steatosis; Graft failure

Core Tip: Paediatrics liver transplantation is primarily dependent on graft availability. Currently there is a gap between is the available grafts and number of children on transplant waiting list resulting in graft shortage. Grafts from obese donors has the risk of hepatic steatosis which could negatively impact transplantation outcomes. Donor obesity should not substitute steatosis work-up as the latter is viewed as independent predictor of graft dysfunction. New strategies to optimize grafts before transplantation might within limits mitigate the risk of using grafts from obese donors.



INTRODUCTION

Paediatric liver transplantation (PLT) is a life-saving procedure for children with underlying advanced liver diseases, including biliary atresia, metabolic liver disorders, and acute liver failure[1-3]. As the only viable option for children with end-stage liver disease or advanced-stage hepatoblastoma, PLT can significantly extend survival and enhance quality of life. However, the success of PLT is heavily dependent on the availability of suitable donor organs[4]. The global rise in obesity makes the decision of accepting a potential graft more challenging, as many donors now present with a body mass index (BMI) classified as obese (BMI > 30 kg/m²)[5,6]. This imposes new challenges for transplant programs, which must balance the graft shortage with the risks associated with donor obesity.

Obesity in liver donors is frequently linked with hepatic steatosis, a condition marked by fat accumulation in liver cells that can impair graft quality by reducing microcirculation and increasing the risk of ischemia-reperfusion injury[7,8]. These factors contribute to a higher likelihood of graft dysfunction and post-transplant complications such as primary non-function, acute rejection, and biliary complications[9-11]. Despite these concerns, recent studies suggest that, with careful management including innovative surgical techniques and strict donor selection criteria, organs from obese donors can achieve comparable outcomes to those from non-obese donors[6,12].

This review was conducted to highlight the recent evidence on the impact of donor obesity in PLT, explore the mechanisms involved, evaluate current management strategies, and suggest future research directions to improve donor selection and patient outcomes.

LITERATURE SEARCH

A comprehensive search was performed across multiple databases, including MEDLINE (via PubMed), Embase, Web of Science, and the Cochrane Library, covering studies from inception through December 2023. Search terms included combinations of "donor obesity", "body mass index", "liver transplantation", and "paediatric", utilizing both Boolean operators and MeSH/Emtree terms. No restrictions on study design were applied, and both living-donor and deceased-donor transplantation studies were considered. The search was limited to English-language publications to ensure accessibility of full texts, and reference lists of included articles were manually screened to identify additional relevant studies.

In order to ensure the quality of the included studies, a quality assessment was performed using the Newcastle-Ottawa Scale for cohort studies and the Jadad scale for randomized controlled trials. The criteria for inclusion were studies focusing on pediatric liver transplant recipients, specifically examining donor obesity and its relation to transplant outcomes. Studies focusing solely on adult recipients and those examining recipient obesity were excluded.

The inclusion/exclusion process was quantitatively measured by screening titles and abstracts first to eliminate irrelevant studies. Following this, a full-text review of the potentially eligible articles was conducted. A study was included if it met the following criteria: (1) Clear definition of donor obesity (BMI > 30 kg/m²); (2) Documented PLT outcomes; and (3) Detailed data on graft function and complications. Any disagreements regarding eligibility were resolved through consensus between the two independent reviewers, ensuring a rigorous and objective process.

DONOR OBESITY AND GRAFT FUNCTION: WHAT DO WE KNOW?

Hepatic steatosis, or fatty liver, is a critical factor when evaluating the suitability of liver grafts from obese donors for PLT[12-14]. When fat accumulation within liver cells exceeds 30%, the risk of primary non-function and graft failure increases substantially. Macrovesicular steatosis, characterized by large fat droplets in hepatocytes, disrupts normal liver metabolism, impairs mitochondrial function, and creates a pro-inflammatory environment. These conditions make the liver more prone to ischemia-reperfusion injury, a leading cause of graft failure in paediatric recipients[13-15].

Evidence demonstrates that donor obesity has a profound impact on graft function in PLT, primarily due to its association with hepatic steatosis. For instance, studies show that donor BMI > 35 kg/m² is associated with a 20%-30% increased risk of primary graft non-function and a 15%-25% increased likelihood of early graft failure compared to grafts from non-obese donors[16,17]. Furthermore, macrosteatosis—fat accumulation exceeding 30% in the donor liver—has been linked to a 30%-40% higher risk of ischemia-reperfusion injury, leading to poorer graft survival[9,11]. Statistical models examining the impact of donor obesity, such as the Donor Risk Index (DRI), demonstrate that obese donors increase the DRI by 5-10 points, significantly influencing post-transplant complications and graft survival[18,19].

Additionally, multivariate analyses incorporating donor BMI, steatosis grade, and recipient factors suggest that while obesity alone may not dramatically reduce long-term survival, its combined effect with steatosis and ischemia significantly elevates the risk of graft dysfunction in the first year post-transplant[14].

Evidence suggests that liver grafts from obese donors with moderate steatosis which is defined by The American Association of Clinical Endocrinologists and the American Association for the Study of Liver Diseases as involving 33% to 66% of liver parenchyma may retain sufficient regenerative capacity under optimal conditions[20-22]. Moderate steatosis, a key component of the non-alcoholic fatty liver disease (NAFLD) activity score, is assessed using diagnostic methods such as ultrasound, controlled attenuation parameter (CAP) with FibroScan, and liver biopsy. CAP values between 233 dB/m and 290 dB/m typically indicate moderate steatosis[23]. Understanding the degree of steatosis is crucial for managing patients with NAFLD or other liver conditions, as it can influence the risk of progression to more severe liver diseases, such as non-alcoholic steatohepatitis and cirrhosis.

Studies show that targeted metabolic therapies and specific dietary regimens before organ retrieval can enhance the condition of fatty livers, minimizing post-transplant complications. Furthermore, the use of donor-specific biomarkers is being explored to better assess liver quality, improving the selection of viable grafts even in the presence of steatosis[24]. This approach promotes a shift from excluding all grafts based only on donor obesity to a more selective strategy that considers various health factors to ensure favorable transplantation outcomes.

Consideration of donor BMI should not substitute the workup for hepatic steatosis, as recent reports suggest that graft macrosteatosis is an independent predictor for early graft dysfunction[16,18]. Consequently, instead of excluding all obese donors, taking into account the degree of hepatic steatosis and other health factors beyond BMI could safely expand the donor pool while maintaining favourable transplantation outcomes[6,15]. This should be practiced with caution in severely obese donors (BMI > 35 kg/m2) as that was independently associated with graft loss and mortality[15]. Due to lack of organ availability and increasing waiting lists for PLT these criteria are under review by the United Kingdom’s Liver Advisory Group in terms of donor weight and BMI.

SURVIVAL OUTCOMES AND COMPLICATIONS: INSIGHTS FROM AVAILABLE REPORTS

The survival outcomes and the complications associated with PLT are substantially influenced by donor obesity, which remains a focal point of interest for transplant teams. Several reports have indicated that liver grafts from donors with a BMI between 25-35 kg/m² do not carry a significantly increased risk of graft failure or mortality compared to grafts from non-obese donors[12,17]. However, the risk profile dramatically changes when the donor's BMI exceeds 35 kg/m², leading to a marked increase in graft loss and patient mortality[15,17]. This increase is attributed to a higher incidence of complications such as primary graft non-function, acute rejection, and biliary complications, suggesting a complex interaction between donor BMI and transplant outcomes in paediatric recipients[12,15,17,25,26].

The elevated risk of complications in grafts from obese donors can be explained by several interrelated factors. Hepatic steatosis, prevalent in obese donors, exacerbates inflammatory responses and compromises liver function post-transplant[15,17]. However, innovative perioperative management strategies, such as optimizing hemodynamic stability and minimizing cold ischemia time, have shown a promising effect in mitigating these risks, thereby allowing for a safer expansion of the donor pool[12,26].

Emerging research suggests the importance of tailoring donor selection and donor management strategies to specific risk profiles rather than excluding all obese donors. Techniques like machine perfusion, which allows for continuous oxygenation and reduces ischemia-reperfusion injury, have been shown to help maintain graft quality even with grafts from obese donors[15,25]. This approach not only preserves the utility of organs from obese donors but also supports a more multifaceted strategy that incorporates factors beyond BMI, such as the degree of hepatic steatosis and overall metabolic health, thus contributing to alleviating organ shortages in PLT[6,15,17,26].

While short-term complications such as graft dysfunction and ischemia-reperfusion injury are well-documented, long-term risks including chronic rejection, biliary complications, and the development of metabolic disorders like insulin resistance and NAFLD are significant concerns[10,14]. Studies indicate that recipients of obese donor livers may experience accelerated fibrosis and reduced graft survival over time[9]. Longitudinal research is needed to evaluate how obesity-related factors, such as increased inflammation and oxidative stress, influence long-term graft function and recipient health[11]. Understanding these long-term outcomes is essential for developing strategies to improve the sustainability of grafts and optimize patient health in the years following transplantation.

HOW DOES HIGH BMI AFFECT LIVING DONORS?

Obesity in liver donors poses several surgical challenges that can significantly affect transplantation outcomes in paediatric patients. Donors with obesity are at a higher risk for perioperative complications such as wound infections, thromboembolic events, delayed recovery, and respiratory problems. These complications can arise from impaired immune responses and reduced tissue perfusion[6,15,27]. The overall approach to overweight donors focuses on counselling and encouragement to lose weight and lead a healthier lifestyle before they are considered for donation in non-urgent liver transplantation circumstances.

To overcome these risks, transplant centres are increasingly adopting advanced surgical techniques specifically designed for obese donors. Minimally invasive approaches, such as laparoscopic and robotic-assisted surgeries, help reduce incision size and tissue trauma, thereby decreasing infection risks and promoting faster recovery[6,25]. Moreover, perioperative strategies like the use of prophylactic antibiotics, aggressive anticoagulation therapy, and early postoperative mobilization are crucial in managing the heightened risk of complications associated with obese donors[6,15]. Optimizing anesthesia protocols and closely monitoring hemodynamic status during surgery further reduce surgical risks, providing a safer environment for paediatric recipients[6].

METABOLIC RISKS FOR PAEDIATRIC RECIPIENTS

Paediatric recipients of liver grafts do not face elevated metabolic risks specifically due to receiving grafts from obese donors. Instead, the development of post-transplant metabolic complications such as metabolic syndrome, insulin resistance, and type 2 diabetes stems from a complex interplay of factors unrelated to the graft. These factors include immunosuppressive therapies, post-transplant lifestyle changes, and pre-existing metabolic conditions in the recipient[12,15]. Current evidence suggests that the recipient's obesity status plays a more significant role. According to NHS Blood and Transplant (NHSBT) guidelines, obesity in transplant recipients is associated with increased postoperative morbidity, including higher rates of infective complications, extended intensive care unit (ICU) and hospital stays, and perioperative issues like vascular and biliary complications[28,29].

While paediatric obesity following liver transplantation is not yet prevalent, understanding how obesity affects adult recipients offers insight into potential risks for children. In adult recipients, overweight and obesity increase the incidence of postoperative infections (60.7% and 65.5%, respectively, compared to 50.4% in normal-weight patients). Morbidly obese patients also experience prolonged ICU and hospital stays, though long-term survival does not differ significantly between obese and non-obese recipients[28,29]. Given these risks, careful monitoring and management of obese paediatric recipients are essential to prevent complications and improve outcomes.

To manage metabolic risks effectively, a multidisciplinary approach is necessary. Routine assessments of blood glucose levels, lipid profiles, and liver function tests, combined with personalized dietary and physical activity programs, are critical. Pharmacological interventions may also be required to address insulin resistance or dyslipidemia. Although optimization of donor livers can be pursued for living donors through pre-retrieval interventions, this option is not available for deceased donors[14].

In summary, while obesity does not preclude liver transplantation, it is associated with increased postoperative complications and longer recovery times, necessitating careful management and monitoring of obese patients undergoing liver transplantation.

PRE-TRANSPLANT INTERVENTIONS: MINIMIZING THE RISKS

Pre-transplant interventions are essential in mitigating the risks associated with using grafts from obese donors for PLT (Table 1). Evidence suggests that structured weight loss programs in living donors, incorporating dietary changes and increased physical activity, can significantly reduce hepatic steatosis and improve liver function, enhancing donor suitability for transplantation. Even modest weight loss has been shown to decrease liver fat content, reduce inflammation, and improve overall liver health, thereby potentially improving graft outcomes[6,24].

Table 1 Strategies to optimize donor grafts.
Optimization Strategy
Description
Potential benefit
Preoperative weight loss programsEncourages weight reduction in living donors to minimize hepatic steatosis riskReduces liver fat content, improving graft function
Normothermic regional perfusionMaintains oxygenation and perfusion in the liver post-retrieval to reduce ischemia-reperfusion injuryEnhances graft quality, reducing early graft dysfunction risk
Ex vivo liver perfusionUtilizes machine perfusion to optimize steatotic grafts and improve viabilityIncreases chances of using grafts from obese donors safely
Steatosis screening via CAP & MRI-PDFFAdvanced imaging techniques used to assess liver fat content and determine graft suitabilityProvides more accurate donor liver assessment, reducing rejection risk

Advancements in non-invasive imaging techniques, such as magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and CAP, have greatly improved the ability to assess hepatic steatosis accurately, allowing for precise measurement of liver fat content[14]. This is crucial in determining the graft suitability for PLT, where even minor discrepancies in graft quality can have significant consequences for young recipients[6,14]. These methods can help the transplant teams to make decisions about accepting or rejecting a graft from obese donors and potentially can expand the donor pool for paediatric recipients[13,14].

Furthermore, transient elastography and ultrasound-based techniques have emerged as effective tools for detecting and quantifying liver steatosis. Transient elastography measures liver stiffness, aiding in the detection of fibrosis and steatosis, and is considered relatively inexpensive and non-invasive. Multiparametric ultrasound approaches further enhance the sensitivity and specificity of steatosis detection, offering a comprehensive evaluation without the need for invasive procedures[30].

In addition, technological innovations in preservation techniques, such as normothermic regional perfusion and ex vivo liver perfusion, have proven effective in optimizing grafts before transplantation. These methods help maintain the liver at physiological temperatures, enhance oxygenation, and minimize ischemia-reperfusion injury, thus improving graft function and viability[14,17,31]. By reconditioning marginal grafts and enhancing their quality, these techniques could significantly expand the donor pool by allowing the safe use of organs from obese donors who might otherwise be excluded[6,15,17].

The impact of graft splitting on the grafts from high BMI donors is still unknown, which is why transplant centers of PLT remain cautious in utilizing grafts from obese donors due to concerns of primary non-function or early vascular or biliary complications.

Besides that, weight management strategies have become an essential consideration in optimizing donor eligibility for liver transplantation, particularly in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). The increasing prevalence of hepatic steatosis among potential donors has necessitated targeted interventions aimed at reducing liver fat content and improving overall graft quality. Evidence suggests that structured dietary modifications, physical activity interventions, and pharmacological therapies can effectively mitigate hepatic fat accumulation, thereby enhancing the suitability of donors for transplantation[32,33]. Given the ongoing shortage of liver grafts, implementing weight reduction strategies may serve as a critical approach to expanding the donor pool, particularly in living donor liver transplantation[34]. Additionally, while these interventions are primarily applicable to living donors, retrospective evaluations of weight management in deceased donors could provide valuable insights into graft viability and long-term transplantation outcomes[33].

Several studies have explored the impact of short-term weight loss interventions on hepatic steatosis in potential liver donors. Systematic reviews and meta-analyses have demonstrated that structured lifestyle modifications, including dietary restrictions and exercise regimens, can significantly reduce liver fat content, leading to improved donor eligibility[34]. In addition to lifestyle interventions, pharmacological approaches have gained increasing attention. Glucagon-like peptide-1 receptor agonists have been shown to improve MASLD outcomes, with clinical trials reporting significant reductions in hepatic fat percentage and improvements in metabolic parameters[35,36]. Furthermore, newer pharmacological agents such as triple hormone receptor agonists have demonstrated enhanced efficacy in reducing liver fat content and improving metabolic function, suggesting their potential application in optimizing donor candidacy[37]. The feasibility of implementing structured, remotely monitored weight reduction programs has also been established, reinforcing the potential of lifestyle interventions in preconditioning liver donors[38]. While weight loss strategies are predominantly applied to living donors, the assessment of weight management history in deceased donors may provide additional prognostic information regarding graft quality[33]. Standardizing preconditioning protocols that integrate dietary, exercise, and pharmacological strategies could play a pivotal role in optimizing donor selection, improving transplantation success rates, and addressing the global shortage of liver grafts[32,33].

An emerging area of interest that has yet to be widely explored is the application of artificial intelligence (AI) and machine learning algorithms to assess and predict graft quality, particularly in organs from obese donors. AI models, trained on extensive datasets of donor and recipient outcomes, could be used to analyze multiple variables such as liver fat content, microcirculation, and overall graft function. These models could help identify marginal livers that may otherwise be excluded, by predicting which grafts are more likely to yield favorable transplant outcomes. By incorporating AI into donor evaluation, transplant teams may be able to make more accurate, individualized decisions, optimizing graft selection and expanding the donor pool in a safer and more efficient manner

BROADER ETHICAL AND PRACTICAL CONSIDERATIONS

Ethically, there is a need to balance the urgent demand for donor organs with the potential risks to both donors and recipients. While expanding donor criteria to include moderately obese individuals could help address the shortage of suitable organs, it is essential to ensure that this does not disproportionately increase the risk of poor outcomes for recipients. Transparent counseling of donors and recipients' families about the risks associated with using grafts from obese donors is crucial for obtaining informed consent and maintaining trust in the transplantation process[6,31]. Useful guidance on these risks and guidance is provided by NHSBT[39].

Ethical considerations are paramount when deciding whether to accept liver grafts from obese donors, especially in pediatric recipients. While expanding the donor pool to include organs from obese donors may alleviate the pressure on waiting lists, the potential risks to the recipient's long-term health must be carefully evaluated. The ethical principle of beneficence supports the use of such grafts when no other suitable options are available. However, the principle of non-maleficence, which urges minimizing harm, raises concerns due to the higher likelihood of graft dysfunction, metabolic complications, and long-term morbidity in recipients of obese donor livers. Furthermore, the principle of autonomy requires that recipients and their families are fully informed of the associated risks and make decisions with a clear understanding of potential long-term outcomes. In addition, justice must guide decisions regarding fair organ allocation, ensuring that transplant criteria do not disproportionately favor one group over another. Therefore, the ethical decision to use organs from obese donors should involve a balanced, transparent approach, considering both immediate survival benefits and potential long-term health implications for pediatric patients.

From a practical standpoint, managing obese donors requires specialized surgical teams and facilities equipped to handle the increased complexity of these cases. This includes access to advanced surgical techniques, appropriate perioperative care, and robust postoperative monitoring to manage the potential complications associated with donor obesity. Developing standardized protocols for evaluating and managing obese donors will be critical to ensuring that the expansion of donor criteria does not compromise the safety or equity of the transplantation process. Such protocols should encompass guidelines for preoperative optimization, intraoperative management, and postoperative care tailored specifically to the unique challenges presented by obese donors[15,31].

Furthermore, the increasing incidence of fatty liver disease and MASLD in children, driven by the rising prevalence of paediatric obesity, may negatively impact the future cadaveric paediatric donor pool. Globally, the prevalence of obesity in children and adolescents aged 5-19 years has increased from 0.7% in 1975 to 5.6% for girls and from 0.9% to 7.8% for boys by 2016, with projections estimating 254 million children and adolescents living with obesity by 2030[40,41]. Although paediatric livers constitute a small proportion of overall organ availability, this trend poses potential challenges for PLT.

Adopting these ethical and practical approaches could help balance the urgent need for organs with the responsibility to ensure the highest safety standards for both donors and recipients in PLT[6,31].

LIMITATIONS

While this review provides a comprehensive analysis of the impact of donor obesity on PLT, several limitations should be acknowledged. First, the existing literature on this topic is limited, with most available studies focusing on adult liver transplantation, necessitating cautious extrapolation of findings to pediatric recipients[15,28]. Furthermore, conflicting data exist regarding the long-term impact of grafts from obese donors, particularly in cases where moderate steatosis is present. While some studies suggest comparable graft survival rates between obese and non-obese donors[15,16], others indicate a higher risk of early allograft dysfunction and post-transplant metabolic complications[11,18]. Additionally, donor BMI alone is an inadequate predictor of graft quality, as hepatic steatosis and other metabolic factors play a more critical role in determining post-transplant outcomes[7,8]. Variability in study methodologies, definitions of steatosis severity, and patient selection criteria further complicate direct comparisons, underscoring the need for multicenter prospective studies to refine donor selection guidelines and improve risk stratification.

FUTURE RESEARCH SUGGESTIONS

Future research should aim to improve the understanding and management of donor obesity in PLT by focusing on several critical areas. Longitudinal studies are needed to assess long-term outcomes for paediatric recipients of grafts from obese donors, particularly concerning growth, development, and metabolic health. The ongoing DeFat study exemplifies such efforts by evaluating strategies to optimize donor liver quality through fat reduction techniques[42]. Insights from this and similar studies will help refine clinical practices and donor selection criteria, ultimately improving outcomes for paediatric recipients[15,17].

Additionally, further investigation into the molecular mechanisms through which donor obesity affects graft function and recipient outcomes is crucial. Understanding these pathways could lead to the development of novel therapeutic approaches aimed at mitigating the risks associated with donor obesity[15,31]. Advancing preservation techniques, such as hypothermic and normothermic machine perfusion, will be essential for safely expanding the donor pool and improving graft viability[12,31].

Future studies should also look into the outcomes of PLT using stratified donor BMI (BMI = 25-35 vs BMI > 35) as authors suggested that donors’ BMI of 25-35 should not be an absolute contra-indication for PLT as it does not seem to negatively affect recipient or graft survival[15].

Moreover, developing comprehensive donor evaluation tools that integrate multiple health variables beyond BMI is imperative. These tools should go beyond simple BMI thresholds and consider the complex interplay of factors affecting donor and graft health. This approach could foster a more holistic strategy for donor selection, ultimately enhancing the safety and success rates of PLT in the context of increasing donor obesity[15].

Additional studies should delve deeper into understanding the biological mechanisms underlying graft dysfunction in PLT, especially in cases involving organs from obese donors. Studies should focus on the molecular pathways affected by hepatic steatosis and inflammation in donor livers, as these factors are known to contribute to ischemia-reperfusion injury and graft failure. Investigating the role of oxidative stress, mitochondrial dysfunction, and immune response modulation in these processes will provide valuable insights into how obesity-related factors influence graft viability[43]. Additionally, studies utilizing genetic and epigenetic analyses could identify biomarkers predictive of graft dysfunction in pediatric recipients. These insights could lead to the development of targeted therapeutic interventions aimed at minimizing graft injury and improving long-term outcomes in pediatric recipients of livers from obese donors. Furthermore, research on novel preservation techniques, such as ex vivo perfusion, in combination with these biological insights, could offer innovative strategies to optimize graft quality before transplantation.

To translate these research findings into clinical practice, transplant centers should implement standardized protocols that incorporate donor steatosis assessments alongside BMI considerations. The adoption of advanced imaging techniques, such as MRI-PDFF and CAP, could improve pre-transplant donor evaluations, allowing for more informed decision-making in marginal graft utilization. Furthermore, integrating machine perfusion technologies in routine clinical practice may serve as a viable approach to optimize steatotic grafts before transplantation, thus broadening donor eligibility criteria. These advancements, alongside structured metabolic optimization programs for potential living donors, will be essential steps toward refining donor selection practices and improving transplant outcomes in paediatric patients. By incorporating these strategies into existing transplantation policies, centers can better navigate the complexities of donor obesity while maintaining graft quality and patient safety.

CONCLUSION

In conclusion, addressing the challenges of donor obesity in PLT requires a multidisciplinary approach that combines innovative clinical practices, advanced imaging and surgical techniques, and robust post-operative care. By embracing collaborative research to understand the long-term effects of donor obesity and develop new preservation strategies, such as machine perfusion, the transplantation community can safely expand the donor pool and improve outcomes. The ultimate goal is to ensure that every child in need of a liver transplant receives the highest quality care and achieves the best possible outcomes, despite the complexities posed by donor obesity.

ACKNOWLEDGEMENTS

The authors would like to express their sincere gratitude to all the researchers, clinicians, and healthcare professionals whose work has contributed to this work. Their dedication and expertise have been instrumental in improving outcomes for children with liver disease. We extend our thanks to the institutions and organizations that have supported research and clinical initiatives in this field. Special appreciation is owed to the families and patients who have participated in studies and clinical trials, as their courage and cooperation have been vital to the progress made in PLT. We also acknowledge the editorial and peer review teams for their valuable feedback and guidance in shaping this review article. Their insights have greatly enhanced the quality and clarity of this work.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Transplantation

Country of origin: United Kingdom

Peer-review report’s classification

Scientific Quality: Grade B, Grade C, Grade C

Novelty: Grade A, Grade B, Grade C

Creativity or Innovation: Grade A, Grade B, Grade C

Scientific Significance: Grade A, Grade B, Grade C

P-Reviewer: Hussain DWG; Labusca L S-Editor: Lin C L-Editor: A P-Editor: Guo X

References
1.  Vilca-melendez H, Mieli-vergani G.   Chapter 26 - Pediatric liver transplantation. In: Organ Transplantation: A Clinical Guide. Klein AA, Lewis CJ, Madsen JC, editors. Cambridge: Cambridge University Press, 2011: 220-230.  [PubMed]  [DOI]  [Full Text]
2.  Vimalesvaran S, Dhawan A. Liver transplantation for pediatric inherited metabolic liver diseases. World J Hepatol. 2021;13:1351-1366.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 3]  [Cited by in RCA: 6]  [Article Influence: 1.5]  [Reference Citation Analysis (2)]
3.  Yoshimaru K, Matsuura T, Yanagi Y, Takahashi Y, Kohashi K, Kaku N, Oda Y, Ohga S, Taguchi T. Successful Urgent Living Donor Liver Transplantation for Massive Liver Necrosis Accompanied by Nonocclusive Mesenteric Ischemia in a Biliary Atresia Infant: A Case Report. Transplant Proc. 2020;52:2802-2808.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Reference Citation Analysis (0)]
4.  Hackl C, Schlitt HJ, Melter M, Knoppke B, Loss M. Current developments in pediatric liver transplantation. World J Hepatol. 2015;7:1509-1520.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 58]  [Cited by in RCA: 51]  [Article Influence: 5.1]  [Reference Citation Analysis (0)]
5.  Parikh ND, Marrero WJ, Wang J, Steuer J, Tapper EB, Konerman M, Singal AG, Hutton DW, Byon E, Lavieri MS. Projected increase in obesity and non-alcoholic-steatohepatitis-related liver transplantation waitlist additions in the United States. Hepatology. 2019;70:487-495.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 65]  [Cited by in RCA: 81]  [Article Influence: 13.5]  [Reference Citation Analysis (0)]
6.  Alnagar AMT, Hajibandeh S, Hajibandeh S, Hakeem AR, Dasari BVM. Impact of Donor Obesity on Graft and Recipient Survival Outcomes After Liver Transplantation: A Systematic Review and Meta-analysis. Transplant Direct. 2024;10:e1656.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Reference Citation Analysis (0)]
7.  Álvarez-Mercado AI, Gulfo J, Romero Gómez M, Jiménez-Castro MB, Gracia-Sancho J, Peralta C. Use of Steatotic Grafts in Liver Transplantation: Current Status. Liver Transpl. 2019;25:771-786.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 25]  [Cited by in RCA: 20]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
8.  Cesaretti M, Addeo P, Schiavo L, Anty R, Iannelli A. Assessment of Liver Graft Steatosis: Where Do We Stand? Liver Transpl. 2019;25:500-509.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 18]  [Cited by in RCA: 22]  [Article Influence: 3.7]  [Reference Citation Analysis (0)]
9.  Hejlova I, Honsova E, Sticova E, Lanska V, Hucl T, Spicak J, Jirsa M, Trunecka P. Prevalence and risk factors of steatosis after liver transplantation and patient outcomes. Liver Transpl. 2016;22:644-655.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 38]  [Cited by in RCA: 38]  [Article Influence: 4.2]  [Reference Citation Analysis (0)]
10.  Cotter TG, Charlton M. Nonalcoholic Steatohepatitis After Liver Transplantation. Liver Transpl. 2020;26:141-159.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 25]  [Cited by in RCA: 45]  [Article Influence: 9.0]  [Reference Citation Analysis (0)]
11.  Alqahtan SA, Brown RS. Management and Risks Before, During, and After Liver Transplant in Individuals With Obesity. Gastroenterol Hepatol (N Y). 2023;19:20-29.  [PubMed]  [DOI]
12.  Perito ER, Glidden D, Roberts JP, Rosenthal P. Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987-2010. Pediatr Transplant. 2012;16:41-49.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 35]  [Cited by in RCA: 31]  [Article Influence: 2.4]  [Reference Citation Analysis (0)]
13.  Tamura S, Sugawara Y, Kokudo N. Donor evaluation and hepatectomy for living-donor liver transplantation. J Hepatobiliary Pancreat Surg. 2008;15:79-91.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 18]  [Cited by in RCA: 18]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
14.  Perito ER, Vase T, Ramachandran R, Phelps A, Jen KY, Lustig RH, Feldstein VA, Rosenthal P. Hepatic steatosis after pediatric liver transplant. Liver Transpl. 2017;23:957-967.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 14]  [Cited by in RCA: 10]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
15.  Perito ER, Rhee S, Glidden D, Roberts JP, Rosenthal P. Impact of the donor body mass index on the survival of pediatric liver transplant recipients and post-transplant obesity. Liver Transpl. 2012;18:930-939.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 11]  [Cited by in RCA: 12]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
16.  Spitzer AL, Lao OB, Dick AA, Bakthavatsalam R, Halldorson JB, Yeh MM, Upton MP, Reyes JD, Perkins JD. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl. 2010;16:874-884.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 244]  [Cited by in RCA: 246]  [Article Influence: 16.4]  [Reference Citation Analysis (0)]
17.  Takagi K, de Wilde RF, Polak WG, IJzermans JNM. The effect of donor body mass index on graft function in liver transplantation: A systematic review. Transplant Rev (Orlando). 2020;34:100571.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 3]  [Cited by in RCA: 7]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
18.  de Graaf EL, Kench J, Dilworth P, Shackel NA, Strasser SI, Joseph D, Pleass H, Crawford M, McCaughan GW, Verran DJ. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. J Gastroenterol Hepatol. 2012;27:540-546.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 118]  [Cited by in RCA: 133]  [Article Influence: 10.2]  [Reference Citation Analysis (0)]
19.  Vogel AS, Roediger R, von Ahrens D, Fortune BE, Schwartz JM, Frager S, Chacko KR, Tow CY. The Impact of Metabolic Health and Obesity on Liver Transplant Candidates and Recipients. Life (Basel). 2024;14.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Reference Citation Analysis (0)]
20.  Han S, Ha SY, Park CK, Joh JW, Kwon CH, Kwon GY, Kim G, Gwak MS, Jeong WK, Ko JS. Microsteatosis may not interact with macrosteatosis in living donor liver transplantation. J Hepatol. 2015;62:556-562.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 21]  [Cited by in RCA: 22]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
21.  Cho JY, Suh KS, Kwon CH, Yi NJ, Cho SY, Jang JJ, Kim SH, Lee KU. The hepatic regeneration power of mild steatotic grafts is not impaired in living-donor liver transplantation. Liver Transpl. 2005;11:210-217.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 43]  [Cited by in RCA: 42]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
22.  Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28:528-562.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 365]  [Cited by in RCA: 512]  [Article Influence: 170.7]  [Reference Citation Analysis (1)]
23.  Cardoso AC, Perez RM, de Figueiredo-Mendes C, Carvalho Leite N, Moraes-Coelho HS, Villela-Nogueira CA. Prevalence and predictive factors of moderate/severe liver steatosis in chronic hepatitis C (CHC) infected patients evaluated with controlled attenuation parameter (CAP). J Viral Hepat. 2018;25:1244-1250.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 7]  [Cited by in RCA: 5]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
24.  Zhao X, He Y, Liu J, Zhang Q, Liu L, Qu W, Liu Y, Zeng Z, Zhang H, Jia J, Sun L, Wei L, Zhu Z. Impact of living donor liver with steatosis and idiopathic portal inflammation on clinical outcomes in pediatric liver transplantation: Beijing experience. Hepatobiliary Surg Nutr. 2022;11:340-354.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Cited by in RCA: 4]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
25.  Alnagar A, Daradka K, Kyrana E, Mtegha M, Palaniswamy K, Rajwal S, Mulla J, O'meara M, Karam M, Shawky A, Hakeem AR, Upasani V, Dhakshinamoorthy V, Prasad R, Attia M. Predictors of patient and graft survival following pediatric liver transplantation: Long-term analysis of more than 300 cases from single centre. Pediatr Transplant. 2022;26:e14139.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 1]  [Cited by in RCA: 1]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
26.  Covarrubias K, Luo X, Massie A, Schwarz KB, Garonzik-Wang J, Segev DL, Mogul DB. Determinants of length of stay after pediatric liver transplantation. Pediatr Transplant. 2020;24:e13702.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 13]  [Cited by in RCA: 7]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
27.  Gunay Y, Guler N, Dayangac M, Taskesen F, Yaprak O, Emek E, Akyildiz M, Altaca G, Yuzer Y, Tokat Y. Living donor liver transplantation for obese patients: challenges and outcomes. Liver Transpl. 2014;20:311-322.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 19]  [Cited by in RCA: 19]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
28.  Hakeem AR, Cockbain AJ, Raza SS, Pollard SG, Toogood GJ, Attia MA, Ahmad N, Hidalgo EL, Prasad KR, Menon KV. Increased morbidity in overweight and obese liver transplant recipients: a single-center experience of 1325 patients from the United Kingdom. Liver Transpl. 2013;19:551-562.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 91]  [Cited by in RCA: 100]  [Article Influence: 8.3]  [Reference Citation Analysis (0)]
29.  Tejedor-Tejada J, Garcia-Pajares F, Safadi R, Mauriz-Barreiro V, Molina E, Juan-Casamayor L, Fernández-Prada S, Helal A, Fuentes-Valenzuela E, Alonso-Martin C, Almohalla-Alvarez C. The impact of obesity on postoperative complications and short-term survival after liver transplantation. Eur J Gastroenterol Hepatol. 2023;35:782-789.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 5]  [Cited by in RCA: 1]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
30.  Pandyarajan V, Gish RG, Alkhouri N, Noureddin M. Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Clinic. Gastroenterol Hepatol (N Y). 2019;15:357-365.  [PubMed]  [DOI]
31.  Goto R, Kawamura N, Watanabe M, Ganchiku Y, Nagatsu A, Okada K, Ito YM, Kamiyama T, Shimamura T, Taketomi A. Long-term risk of a fatty liver in liver donors. Ann Gastroenterol Surg. 2023;7:645-653.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 4]  [Reference Citation Analysis (0)]
32.  Chung JH, Ryu JH, Yang KH, Choi BH, Park Y, Lee TB, Shim JR, Ko HJ, Cho SH. Efficacy and Safety of Weight Reduction of the Donor in Hepatic Steatosis for Living Donor Liver Transplantation. Ann Transplant. 2020;25:e923211.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 1]  [Cited by in RCA: 3]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
33.  Imamura H, Sano K, Saiura A. Reconsiderations for the liver donation from a living donor: addressing hepatic steatosis with weight loss preconditioning. Hepatol Int. 2024;18:1382-1384.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Reference Citation Analysis (0)]
34.  Trakroo S, Bhardwaj N, Garg R, Modaresi Esfeh J. Weight loss interventions in living donor liver transplantation as a tool in expanding the donor pool: A systematic review and meta-analysis. World J Gastroenterol. 2021;27:3682-3692.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in CrossRef: 18]  [Cited by in RCA: 18]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
35.  Havranek B, Loh R, Torre B, Redfield R, Halegoua-DeMarzio D. Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes. Sci Rep. 2025;15:4947.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Reference Citation Analysis (0)]
36.  Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA; NN9931-4296 Investigators. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2021;384:1113-1124.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 513]  [Cited by in RCA: 1117]  [Article Influence: 279.3]  [Reference Citation Analysis (0)]
37.  Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30:2037-2048.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Reference Citation Analysis (0)]
38.  Rose JT, Vargas P, Seay T, Pesch AJ, Williams T, Sites A, Henry Z, Northup PG, Pelletier SJ, Oberholzer J, Argo CK, Goldaracena N. Lose Weight to Donate: Development of a Program to Optimize Potential Donors With Hepatic Steatosis or Obesity for Living Liver Donation. Transplant Direct. 2021;7:e702.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Full Text (PDF)]  [Cited by in Crossref: 1]  [Cited by in RCA: 1]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
39.  NHS Blood and Transplant  Organ transplantation: Risks from the donated liver. [cited 25 October 2024]. Available from: https://www.nhsbt.nhs.uk/organ-transplantation/liver/receiving-a-liver/risks-from-the-donated-liver/.  [PubMed]  [DOI]
40.  Jebeile H, Kelly AS, O'Malley G, Baur LA. Obesity in children and adolescents: epidemiology, causes, assessment, and management. Lancet Diabetes Endocrinol. 2022;10:351-365.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 39]  [Cited by in RCA: 404]  [Article Influence: 134.7]  [Reference Citation Analysis (0)]
41.  Lobstein T. Obesity prevention and the Global Syndemic: Challenges and opportunities for the World Obesity Federation. Obes Rev. 2019;20 Suppl 2:6-9.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 3]  [Cited by in RCA: 7]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
42.  Clinical Trials Unit  DeFat. [cited 25 October 2024]. Available from: https://www.nhsbt.nhs.uk/clinical-trials-unit/trials-and-studies/organ-donation-and-transplantation/defat/.  [PubMed]  [DOI]
43.  Barbetta A, Rocque B, Bangerth S, Street K, Weaver C, Chopra S, Kim J, Sher L, Gaudilliere B, Akbari O, Kohli R, Emamaullee J. Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection. Sci Adv. 2024;10:eadm8841.  [RCA]  [PubMed]  [DOI]  [Full Text]  [Cited by in Crossref: 2]  [Reference Citation Analysis (0)]