Liver transplantation remains a life-saving therapy for a growing list of indications. Although 10,660 adult liver transplants were performed in the United States in 2023, a 50% increase over the preceding decade, the demand continues to far exceed the supply. Efforts to expand the liver donor pool by using donors that were previously considered unsuitable have remained an important strategy to help overcome shortages. We discuss the progress that has been made over the past decade, as well as potential future barriers that will need to be overcome to help successfully expand the liver donor pool.

Transplantation of the left lateral section (LLS) of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children, with variants of the LLS primarily used in infants. However, the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant. This review explores historical developments, various approaches to measuring the required functional liver mass, and techniques to prevent complications associated with large-for-size grafts in infants.

Over the past six decades, liver transplantation (LT) has evolved from an experimental procedure into a standardized and life-saving intervention, reshaping the landscape of organ transplantation. Driven by pioneering breakthroughs, technological advancements, and a deepened understanding of immunology, LT has seen remarkable progress. Some of the most notable breakthroughs in the field include advances in immunosuppression, a revised model for end-stage liver disease, and artificial intelligence (AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT, paired with ever-evolving technological advances. Additionally, the refinement of transplantation procedures, resulting in the introduction of alternative transplantation methods, such as living donor LT, split LT, and the use of marginal grafts, has addressed the challenge of organ shortage. Moreover, precision medicine, guiding personalized immunosuppressive strategies, has significantly improved patient and graft survival rates while addressing emergent issues, such as short-term complications and early allograft dysfunction, leading to a more refined strategy and enhanced post-operative recovery. Looking ahead, ongoing research explores regenerative medicine, diagnostic tools, and AI to optimize organ allocation and post-transplantation car. In summary, the past six decades have marked a transformative journey in LT with a commitment to advancing science, medicine, and patient-centered care, offering hope and extending life to individuals worldwide.

Extracorporeal liver surgery (ELS), also known as liver autotransplantation, is a hybrid (cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation (ELRA), ante-situm liver resection and autotransplantation (ALRA) and auxiliary partial liver autotransplantation (APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous efforts done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.

Living donor liver transplantation (LT) and deceased donor split-LT often result in congestion within liver grafts. The regenerative process and function of congested areas, especially graft congestion associated with LT, are not well understood. Therefore, we created new rat models with congested areas in partially resected livers and orthotopically transplanted these livers into syngeneic rats to observe liver regeneration and function in congested areas. This study aimed to compare liver regeneration and the function of congested areas after liver resection and LT, and to explore a new approach to ameliorate the adverse effects of graft congestion. Although the congested areas after liver resection regenerated normally on postoperative day 7, the congested areas after LT had poor regeneration with abscess development on postoperative day 7. Necrotic areas in congested areas were larger after LT than after liver resection on postoperative days 1, 3, and 7 ( p < 0.05, p < 0.05, and p < 0.01, respectively). Although congested areas after liver resection did not affect survival, in the LT model, the survival of rats with congested areas was significantly poorer even with larger grafts than that of rats with smaller noncongested grafts ( p = 0.04). Hepatocyte growth factor administration improved the survival rate of rats with congested grafts from 41.7% to 100%, improved the regeneration of congested areas, and significantly reduced the size of necrotic areas ( p < 0.05). Thus, congested areas in liver grafts may negatively impact recipients. Short-term administration of hepatocyte growth factor may improve postoperative outcomes of recipients with graft congestion and contribute to more effective use of liver grafts (approval number: MedKyo-23137, Institutional Ethics Committee/Kyoto University).

The increasing morbidity of liver cancer has led to a growing demand for transplantation. Split liver transplantation (SLT) is a promising way to ameliorate organ shortages. However, the safety and efficacy of SLT are still controversial. The aim of this study was to assess the clinical outcome of SLT in liver cancer patients at our center.

A total of 74 patients who received liver transplantation at a tertiary hospital from March 2019 to July 2023 were retrospectively studied, of whom 37 recipients underwent SLT and 37 recipients underwent whole-graft liver transplantation (WGLT). Clinical data were analyzed and compared between patients who underwent SLT and WGLT.

SLT and WGLT were successfully performed, with no intraoperative transplant-related mortality. Postoperatively, no significant differences in total bilirubin (TB, P=0.266), alanine transaminase (ALT, P=0.403) and aspartate transaminase (AST, P=0.160) levels within 30 d were detected between the two groups. The transplant-related mortality rates were 8.1% in the SLT group and 5.4% in the WGLT group within 30 d of surgery (P=1.000), and 10.8% and 8.1%, respectively, at 90 d after surgery (P=1.000). There were no significant differences in overall survival (OS) and progress-free survival (PFS) between the SLT and WGLT groups (P=0.910, P=0.190).

Our results show that SLT does not imply additional risks in treating liver cancer compared with WGLT.

This study aimed to evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) within 3 days postoperative can identify 1-month graft failure after split liver transplantation (SLT).

A total of 58 consecutive patients who underwent SLT between February 2022 and September 2023 were included. The DUS and CEUS images and parameters within 3 days postoperatively were analyzed and recorded. The DUS parameters included peak systolic velocity (PSV), resistive index, and systolic acceleration time for the hepatic artery and PSV for the portal vein and hepatic vein. The CEUS qualitative analysis variables included the liver parenchyma enhancement pattern and the posterior enhancement attenuation. Logistic regression and Cox proportional hazard regression were used to evaluate the relationship between DUS/CEUS findings and 1-month graft failure.

Seven of the 58 liver grafts failed within 1 month. Poor CEUS enhancement (pattern Ⅱ/Ⅲ) was observed in five of seven patients (71.4%) of graft failure, whereas good contrast enhancement (pattern Ⅰ) was found in 47 of the 51 patients (92.1%) in the successful group on postoperative day 3. Multivariate logistic regression analysis revealed that 1-month graft failure was independently predicted by operative time (odds ratio [OR] = 3.79, 95% confidence interval [CI]: 1.27-11.29, p = .017) and CEUS enhancement pattern on postoperative day 3 (OR = 90.88, 95% CI: 2.77-2979.56, p = .011). Cox proportional hazard regression showed that operative time (hazard ratio [HR] = 1.6, 95% CI: 1.15-2.22, p = .005) and CEUS enhancement pattern on postoperative day 3 (HR = 11.947, 95% CI: 2.04-69.98, p = .006) were independent predictors for graft failure.

Poor CEUS enhancement (pattern Ⅱ/Ⅲ) was associated with 1-month graft failure in SLT recipients. CEUS may serve as a noninvasive, valuable prognostic tool to predict clinical outcomes early after SLT.

Recent advances in machine perfusion have revolutionised the field of transplantation by prolonging preservation, permitting evaluation of viability prior to implant and rescue of discarded organs. Long-term perfusion for days-to-weeks provides time to modify these organs prior to transplantation. By using long-term normothermic machine perfusion to facilitate liver splitting and subsequent perfusion of both partial organs, possibilities even outside the clinical arena become possible. This model remains in its infancy but in the future, could allow for detailed study of liver injury and regeneration, and ex-situ treatment strategies such as defatting, genetic modulation and stem-cell therapies. Here we provide insight into this new model for research and highlight its great potential and current limitations.

Liver transplantation is the only life-saving procedure for children with end-stage liver disease. The field is however heterogenic with various graft types, recipient age, weight, and underlying diseases. Despite recently improved overall outcomes and the expanded use of living donors, waiting list mortality remains unacceptable, particularly in small children and infants. Based on the known negative effects of elevated donor age, higher body mass index, and prolonged cold ischemia time, the number of available donors for pediatric recipients is limited. Machine perfusion has regained significant interest in the adult liver transplant population during the last decade. Ten randomized controlled trials are published with an overall advantage of machine perfusion techniques over cold storage regarding postoperative outcomes, including graft survival. The concept of hypothermic oxygenated perfusion (HOPE) was the first and only perfusion technique used for pediatric liver transplantation today. In 2018 the first pediatric candidate received a full-size graft donated after circulatory death with cold storage and HOPE, followed by a few split liver transplants after HOPE with an overall limited case number until today. One series of split procedures during HOPE was recently presented by colleagues from France with excellent results, reduced complications, and better graft survival. Such early experience paves the way for more systematic use of machine perfusion techniques for different graft types for pediatric recipients. Clinical reports of pediatric liver transplants with other perfusion techniques are awaited. Strong collaborative efforts are needed to explore the effect of perfusion techniques in this vulnerable population impacting not only the immediate posttransplant outcome but the development and success of an entire life.

Historically, pediatric liver transplantation has achieved significant milestones, yet recent innovations have predominantly occurred in adult liver transplantation due to higher caseloads and ethical barriers in pediatric studies. Emerging methods subsumed under the term artificial intelligence offer the potential to revolutionize data analysis in pediatric liver transplantation by handling complex datasets without the need for interventional studies, making them particularly suitable for pediatric research. This review provides an overview of artificial intelligence applications in pediatric liver transplantation. Despite some promising early results, artificial intelligence is still in its infancy in the field of pediatric liver transplantation, and its clinical implementation faces several challenges. These include the need for high-quality, large-scale data and ensuring the interpretability and transparency of machine and deep learning models. Ethical considerations, such as data privacy and the potential for bias, must also be addressed. Future directions for artificial intelligence in pediatric liver transplantation include improving donor-recipient matching, managing long-term complications, and integrating diverse data sources to enhance predictive accuracy. Moreover, multicenter collaborations and prospective studies are essential for validating artificial intelligence models and ensuring their generalizability. If successfully integrated, artificial intelligence could lead to substantial improvements in patient outcomes, bringing pediatric liver transplantation again to the forefront of innovation in the transplantation community.

Normothermic liver machine perfusion (NLMP) is advancing the field of liver transplantation (LT). Beyond improved preservation and organ assessment, NLMP helps to increase organ utilization. We herein address the feasibility and merit of NLMP in split liver transplantation (SLT) to postpone the transplantation of the second split graft to the following day.

We analyzed the perfusion characteristics and outcomes of all consecutive adult recipients who underwent SLT following NLMP from February 1, 2018, to June 30, 2023. The primary endpoint was 90-d graft and patient survival. Secondary endpoints were posttransplant complications and 90-d morbidity.

Three right and 3 extended right SLT following NLMP have been performed. NLMP was uneventful in all cases. Perfusion characteristics differed according to graft volume. Mean perfusion time was 17:00 h (±05:13) and bile production ranged between 8 and 21 mL/h. All split grafts fulfilled predefined center viability criteria during NLMP and were transplanted on the following day. The 90-d graft and patient survival rate was 100%. Three patients (50%) required an early relaparotomy, and 2 patients (33.3%) developed biliary complications. The 90-d morbidity as recorded by the comprehensive complication index was 62.7 (±24.7).

NLMP of split liver grafts is technically feasible and safe. Through prolongation of preservation time, NLMP allows to safely postpone transplantation of the second split liver graft to the next day.

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.

This editorial contains comments on the article "Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature" in the recent issue of World Journal of Gastrointestinal Surgery. It points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation (ELRAT) and systemic therapy, underlying molecular mechanisms for targeted therapy in perihilar cholangiocarcinoma (pCCA) management. pCCA is a tough malignancy with a high proportion of advanced disease at the time of diagnosis. The only curative option is radical surgery. Surgical excision and reconstruction become extremely complicated and not always could be performed even in localized disease. On the other hand, ELRAT takes its place among surgical options for carefully selected pCCA patients. In advanced disease, systemic therapy becomes a viable option to prolong survival. This editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with kinase inhibitors and immunotherapy in both palliative and adjuvant settings. Fibroblast grow factor and fibroblast grow factor receptor, human epidermal growth factor receptor 2, isocitrate dehydrogenase, and protein kinase cAMP activated catalytic subunit alpha (PRKACA) and beta (PRKACB) pathways have been actively investigated in CCA in last years. Several agents were introduced and approved by the Food and Drug Administration. They all demonstrated meaningful activity in CCA patients with no global change in outcomes. That is why every successfully treated patient counts, especially those with advanced disease. In conclusion, pCCA is still hard to treat due to late diagnosis and extremely complicated surgical options. ELRAT also brings some hope, but it could be performed in very carefully selected patients. Advanced disease requires systemic anticancer treatment, which is supposed to be individualized according to the genetic and molecular features of cancer cells. Targeted therapy in combination with chemo-immunotherapy could be effective in susceptible patients.

Technical variant liver transplantation (TVLT) is a strategy to mitigate persistent pediatric waitlist mortality in the United States, although its implementation remains stagnant. This study investigated the relationship between TVLT utilization, transplant center volume, and graft survival.

Pediatric liver transplant recipients from 2010 to 2020 (n = 5208) were analyzed using the Scientific Registry of Transplant Recipients database. Transplant centers were categorized according to the average number of pediatric liver transplants performed per year (high-volume, ≥5; low-volume, <5). Graft survival rates were compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were used to identify predictors of graft failure.

High-volume centers demonstrated equivalent whole liver transplant and TVLT graft survival ( P = 0.057) and significantly improved TVLT graft survival compared with low-volume centers ( P < 0.001). Transplantation at a low-volume center was significantly associated with graft failure (adjusted hazard ratio, 1.6; 95% confidence interval, 1.14-2.24; P = 0.007 in patients <12 y old and 1.8; 95% confidence interval, 1.13-2.87; P = 0.013 in patients ≥12 y old). A subset of high-volume centers with a significantly higher rate of TVLT use demonstrated a 23% reduction in waitlist mortality.

Prompt transplantation with increased TVLT utilization at high-volume centers may reduce pediatric waitlist mortality without compromising graft survival.

Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.

Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time.

The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993-2005, 2006-2014, and 2015-2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period.

SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25-50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001).

Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure.

Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all consecutive in situ SLTs performed in Italy from May 1993 to December 2019. With more than 1,700 cases, it is one of the largest series, examining long-term national trends in in situ SLT since its introduction. The data presented indicate that the outcomes of SLT improved during this 25-year period. Improvements are probably due to better recipient selection, refinements in surgical technique, conservative graft-to-recipient matching, and the continuous, yet carefully managed, expansion of donor selection criteria under a strict mandatory split liver allocation policy. These results could help to dispel reservations regarding the use of this procedure.

Recently, efforts have been made to recognize the precise reason(s) for transplant failure and the process of rejection utilizing the molecular signature. Most transplant recipients do not appreciate the unknown length of survival of allogeneic grafts with the existing standard of care. Two noteworthy immunological pathways occur during allogeneic transplant rejection. A nonspecific innate immune response predominates in the early stages of the immune reaction, and allogeneic antigens initiate a donor-specific adaptive reaction. Though the adaptive response is the major cause of allograft rejection, earlier pro-inflammatory responses that are part of the innate immune response are also regarded as significant in graft loss. The onset of the innate and adaptive immune response causes chronic and acute transplant rejection. Currently employed immunosuppressive medications have shown little or no influence on chronic rejection and, as a result, on overall long-term transplant survival. Furthermore, long-term pharmaceutical immunosuppression is associated with side effects, toxicity, and an increased risk of developing diseases, both infectious and metabolic. As a result, there is a need for the development of innovative donor-specific immunosuppressive medications to regulate the allorecognition pathways that induce graft loss and to reduce the side effects of immunosuppression. Efferocytosis is an immunomodulatory mechanism with fast and efficient clearance of apoptotic cells (ACs). As such, AC therapy strategies have been suggested to limit transplant-related sequelae. Efferocytosis-based medicines/treatments can also decrease the use of immunosuppressive drugs and have no detrimental side effects. Thus, this review aims to investigate the impact of efferocytosis on transplant rejection/tolerance and identify approaches using AC clearance to increase transplant viability.

In some pediatric patients undergoing living-donor liver transplantation, segment IV without the middle hepatic vein can be added to a left lateral segment graft to obtain larger graft volume. Because no clear consensus on this technique exists, this study investigated the effects of congested areas on postoperative outcomes in pediatric patients with biliary atresia undergoing living-donor liver transplantation.

We retrospectively reviewed data of recipients with biliary atresia aged ≤15 y who had undergone living-donor liver transplantation at Kyoto University Hospital between 2006 and 2021 and with graft-to-recipient weight ratios (GRWR) of ≤2%. Based on the percentage of congested area in the graft, patients were classified into the noncongestion (n = 40; ≤10%) and congestion (n = 13; >10%) groups. To compare the differences between groups with similar nooncongestive GRWRs and investigate the effect of adding congested areas, patients in the noncongestion group with GRWRs of ≤1.5% were categorized into the small noncongestion group (n = 24).

GRWRs and backgrounds were similar between the noncongestion and congestion groups; however, patients in the congestion group demonstrated significantly longer prothrombin times, higher ascites volumes, and longer hospitalization. Further, compared with the small noncongestion group, the congestion group had significantly greater GRWR and similar noncongestive GRWR; however, the congestion group had significantly longer prothrombin time recovery (P = 0.020, postoperative d 14), higher volume of ascites (P < 0.05, consistently), and longer hospitalization (P = 0.045), requiring significantly higher albumin and gamma-globulin transfusion volumes than the small noncongestion group (P = 0.027 and P = 0.0083, respectively). Reoperation for wound dehiscence was significantly more frequent in the congestion group (P = 0.048).

In pediatric liver-transplant recipients, adding a congested segment IV to the left lateral segment to obtain larger graft volume may negatively impact short-term postoperative outcomes.

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava (RHIVC) and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.

In patients undergoing liver transplantation for metabolic diseases, removing the patient's liver for transplantation to another recipient is called "domino liver transplantation." The extracted liver can be divided and transplanted into 2 recipients, which is called domino split-liver transplantation in the literature. However, in our study, the domino liver was obtained from a pediatric patient.

A patient with maple syrup urine disease (MSUD) underwent a living donor liver transplant, and the explanted liver was divided in situ into right and left lobes and transplanted to 2 separate patients. Demographic data, surgical techniques, postoperative period, and patient follow-ups were evaluated.

The father's left lobe liver graft was transplanted into a 12-year-old boy with MSUD. The removed liver was divided in situ into right and left lobes. The left lobe was transplanted to a 14-year-old male patient, whereas the right lobe was transplanted to a 67-year-old male patient. The donor and the first recipient were discharged on postoperative days 5 and 22. The second pediatric patient who underwent domino split-left lobe transplantation was discharged on postoperative day 23. The adult patient who underwent domino split-right lobe transplantation died on postoperative day 12 owing to massive esophageal variceal bleeding.

Patients who underwent liver transplantation due to MSUD are among the best donor choices for domino liver transplantation. If the extracted liver has a sufficient volume and anatomic features for a split, it can be used in "selected cases."

Tumor infiltration of the hepatic outflow comprising all three hepatic veins and the inferior vena cava remains a surgical challenge. Liver resection under total vascular exclusion with or without extracorporeal bypass has been described as a therapeutic option for these tumors. Here, we present our experience with these complex surgical methods.

We searched our database for patients treated with an in-situ or ante-situm liver resection (ISR and ASR, respectively) with extracorporeal bypass. We collected demographic and perioperative data.

From January 2010 to December 2021, we performed 2122 liver resections. Nine patients were treated with ASR and five were treated with ISR. Out of these 14 patients, six had colorectal liver metastases, six had cholangiocarcinoma, and two had non-colorectal liver metastases. The median operative time and bypass time in all patients were 536.5 and 150 min, respectively. Compared with ISR, ASR required a longer operative time (ASR 586 min and ISR 495 min) and a longer bypass time (ASR 155 min and ISR 122 min). Morbidity (Clavien-Dindo grade > 3A adverse events) occurred in 78.5% of patients. 90-day postoperative mortality was 7%. Median overall survival was 33 months. Seven patients experienced recurrence. In these patients, median disease-free survival was 9 months.

Resection of tumors infiltrating the hepatic outflow poses a high risk for patients. However, with rigorous selection and an experienced perioperative team, these patients can be treated surgically with reasonable oncological outcomes.

Split liver transplantation (SLT), where a single donor liver is divided for transplantation to 2 recipients, has the potential to increase the availability of size-matched livers for pediatric candidates and expand the supply of donor organs available for adult candidates. Although SLT is a well-established technique, the number of SLTs has remained flat during the past 2 decades, partly due to concerns about the posttransplant survival of SLT recipients compared with whole liver transplantation (WLT) recipients. Prior work on SLT versus WLT survival analysis had limitations because, for pediatric recipients, it did not consider the correlations between donor age/weight and the allograft type, and for adult recipients, it may have included records where the donor livers did not meet the split liver criteria (splittable).

Using the Organ Procurement and Transplantation Network's database (2003-2019), this study analyzes and compares (i) key characteristics of donors and recipients, (ii) donor-recipient match dynamics (organ offers and accept/decline decisions), and (iii) recipient posttransplant survival, for SLT and WLT.

The results in this study show that the posttransplant survival of SLT and WLT recipients is similar (controlling for other confounding factors that may impact posttransplant survival), highlighting the importance of SLT for increasing the liver supply and potential benefits for both pediatric and adult candidates.

Liver disease is increasing in incidence and is the third most common cause of premature death in the United Kingdom and fourth in the United States. Liver disease accounts for 2 million deaths globally each year. Three-quarters of patients with liver disease are diagnosed at a late stage, with liver transplantation as the only definitive treatment. Thomas E. Starzl performed the first human liver transplant 60 years ago. It has since become an established treatment for end-stage liver disease, both acute and chronic, including metabolic diseases and primary and, at present piloting, secondary liver cancer. Advances in surgical and anaesthetic techniques, refined indications and contra-indications to transplantation, improved donor selection, immunosuppression and prognostic scoring have allowed the outcomes of liver transplantation to improve year on year. However, there are many limitations to liver transplantation. This review describes the milestones that have occurred in the development of liver transplantation, the current limitations and the ongoing research aimed at overcoming these challenges.

Liver transplantation is a life-saving treatment for end-stage pediatric liver failure. We aimed to present the results of pediatric liver transplants performed in our center in the last 11 years (between 2012 and March 2022) in association with prognostic factors affecting survival.

Demographic characteristics, etiologic reasons, previous operations (Kasai procedure), morbidity, mortality, survival, and bilio-vascular complication rates were determined, and outcomes were evaluated. In the postoperative period, the duration of mechanical ventilation and intensive care unit stay and surgical and other complications were evaluated. Graft and patient survival rates were determined, and univariate and multivariate factors affecting these rates were evaluated.

In the last 10 years, 229 pediatric liver transplantaion (Pe-LT)/1513 adult liver taransplantation (Ad-LT) (21.35%) were performed in our center. This ratio (Pe-LT/Ad-LT ratio) is 1741/15,886 (10.95%) for our country. A total of 229 liver transplants were performed in 214 pediatric patients. Retransplantation was performed in 15 patients (6.55%). Cadaveric liver transplantation was performed in 9 patients. Graft survival rates were 87%, 83%, 78%, 78%, 78%, and 78% at <30 days, 30 to 90 days, 91 to 364 days, 1 to 3 years, and >3 years, respectively. Patient survival rates for <30 days, 30 to 90 days, 91 to 364 days, 1 to 3 years, and >3 years were 91.5%, 85.7%, 82%, 81.5%, and 81.5%, respectively. Our 5-year survival rates in metabolic diseases and the acute fulminant failure group are 93.8% and 100%, respectively.

The fact that the 1- and 5-year survival rates are the same shows that when patients overcome biliary vascular and infectious problems, their survival is prolonged.

The liver is a complicated organ within the body that performs wide-ranging and vital functions and also has a unique regenerative capacity after hepatic tissue injury and cell loss. Liver regeneration from acute injury is always beneficial and has been extensively studied. Experimental models including partial hepatectomy (PHx) reveal that extracellular and intracellular signaling pathways can help the liver recover to its equivalent size and weight prior to an injury. In this process, mechanical cues possess immediate and drastic changes in liver regeneration after PHx and also serve as main triggering factors and significant driving forces. This review summarized the biomechanics progress in liver regeneration after PHx, mainly focusing on PHx-based hemodynamics changes in liver regeneration and the decoupling of mechanical forces in hepatic sinusoids including shear stress, mechanical stretch, blood pressure, and tissue stiffness. Also discussed were the potential mechanosensors, mechanotransductive pathways, and mechanocrine responses under varied mechanical loading in vitro. Further elucidating these mechanical concepts in liver regeneration helps establish a comprehensive understanding of the biochemical factors and mechanical cues in this process. Proper adjustment of mechanical loading within the liver might preserve and restore liver functions in clinical settings, serving as an effective therapy for liver injury and diseases.

Graft-recipient size matching is a major challenge in pediatric liver transplantation, especially for adolescent recipients. Indeed, adolescents have the lowest transplantation rate among pediatric recipients, despite prioritization policies and the use of split grafts. In case of an important graft-recipient size mismatch, ex situ graft reduction with right posterior sectionectomy (RPS) may optimize the available donor pool to benefit adolescent recipients.

We present three cases of liver graft reduction with ex situ RPS for adolescent recipients. The surgical strategy was guided by GRWR (graft/recipient weight ratio), GW/RAP (right anteroposterior distance ratio), and CT-scan volumetric and anthropometric evaluation.

Recipients were 12, 13, and 14-year-old and weighed 32, 47, and 35 kg, respectively. All liver grafts were procured from brain-dead donors with a donor/recipient weight ratio >1.5. RPS was performed ex situ, removing 20% of the total liver volume leading to a decrease of the GRWR <4% and the GW/RAP <100 g/cm in each case. All three reduced grafts were successfully transplanted with a static cold storage time ranging from 390 to 510 min without the need for delayed abdominal closure. We did not observe any primary non-function, vascular complication, or delayed graft function with a median follow-up of 6 months. One biliary anastomotic stenosis occurred which required surgical treatment.

Ex situ liver graft reduction with RPS allowed for successful transplantation in case of anthropometric graft-recipient size mismatch in adolescent liver transplant candidates. Although the use of split grafts remains the gold standard, RPS should be acknowledged as a way to optimize the donor pool, especially for adolescent recipients.

The utilization of split liver grafts can increase access to liver transplantation (LT) for adult patients, particularly when liver grafts are shared between 2 adult recipients. However, it is yet to be determined whether split liver transplantation (SLT) increases the risk of biliary complications (BCs) compared with whole liver transplantation (WLT) in adult recipients. This retrospective study enrolled 1441 adult patients who underwent deceased donor LT at a single-site between January 2004 and June 2018. Of those, 73 patients underwent SLTs. Graft type for SLT includes 27 right trisegment grafts, 16 left lobes, and 30 right lobes. A propensity score matching analysis selected 97 WLTs and 60 SLTs. Biliary leakage was more frequently seen in SLTs (13.3% vs. 0%; p <0.001), whereas the frequency of biliary anastomotic stricture was comparable between SLTs and WLTs (11.7% vs. 9.3%; p=0.63). Graft and patient survival rates of patients undergoing SLTs were comparable to those undergoing WLTs (p=0.42 and 0.57, respectively). In the analysis of the entire SLT cohort, BCs were seen in 15 patients (20.5%) including biliary leakage in 11 patients (15.1%) and biliary anastomotic stricture in 8 patients (11.0%) [both in 4 patients (5.5%)]. The survival rates of recipients who developed BCs were significantly inferior to those without BCs (p <0.01). By multivariate analysis, the split grafts without common bile duct increased the risk of BCs. In conclusion, SLT increases the risk of biliary leakage compared with WLT. Biliary leakage can still lead to fatal infection and thus should be managed appropriately in SLT.

The shortage of donors' livers for pediatric recipients inspired the search for alternatives including donation after cardiac death (DCD).

Retrospective review of pediatric liver transplant (PLT) using DCD grafts. Patients were divided into either FLG or RLG recipients. Pre-transplant recipient parameters, donor parameters, operative parameters, post-transplant recipient parameters, and outcomes were compared.

Overall, 14 PLTs from DCD donors between 2005 and 2018 were identified; 9 FLG and 5 RLG. All donors were Maastricht category III. Cold ischemia time was significantly longer in RLG (8.2 h vs. 6.2 h; p = .038). Recipients of FLG were significantly older (180 months vs. 7 months; p = .012) and waited significantly longer (168 days vs. 22 days; p = .012). Recipients of RLG tended to be sicker in the immediate pre-transplant period and this was reflected by the need for respiratory or renal support. There was no significant difference between groups regarding long-term complications. Three patients in each group survived more than 5 year post-transplant. One child was re-transplanted in the RLG due to portal vein thrombosis but failed to survive after re-transplant. One child from FLG also died from a non-graft-related cause.

Selected DCD grafts are an untapped source to widen the donor pool, especially for sick recipients. In absence of agreed criteria, graft and recipient selection for DCD grafts should be undertaken with caution.

Split liver transplantation (SLT) is a strategy to address organ shortage, but is a technically more demanding procedure than whole graft liver transplantation (LT). We aimed to determine the outcomes following SLT in adult recipients as well as to highlight the impact that having a pediatric LT program has on SLT implementation.

All SLTs conducted at a single-center from 2010 to 2019 were identified. Patient data was obtained through retrospective review of the electronic medical record. Kaplan-Meier analysis assessed primary outcomes of 1-,3-, and 5-year graft and patient survival.

We identified 37 SLTs performed at our institution from 2010 to 2019. Twenty-four donated livers resulted in 21 extended right lobes and 16 left lateral segments for adults and pediatrics recipients, respectively. Eighty-one percent (30/37) of the SLTs were performed after introduction of the combined pediatric program in 2016. 13/24 donor livers were split with both grafts allocated and used at our institution and 92% occurred after introduction of the pediatric program. Graft survival rates at 1-, 3-, and 5-years were 94% in adult recipients and 100% for all time periods in pediatric recipients. Actuarial post-transplant patient survival was 100% at 1-, 3-, and 5-years in both.

The introduction of a pediatric liver transplantation program resulted in more than a fourfold increase in the number of SLTs performed at our center. Increase in allocation and use of both grafts at our institution was also seen.

Over the last decades, liver transplantation (LT) has evolved into a life-saving procedure. Due to limited deceased donor activities in the eastern world, living donor liver transplantation (LDLT) had flourished tremendously in most Asian countries. Yet, these LDLT activities fall short of meeting the expected demands. Pakistan, a developing country, bears a major burden of liver diseases. Currently, only few centers offer LDLT services in the country. On the other hand, deceased donor liver transplantation (DDLT) activities have not started due to social, cultural, and religious beliefs. Various strategies can be adopted successfully to overcome the scarcity of live liver donors (LLDs) and to expand the donor pool, keeping in view donor safety and recipient outcome. These include consideration of LLDs with underlying clinical conditions like G6PD deficiency and Hepatitis B core positivity. Extended donor criteria can also be utilized and relaxation can be made in various donors' parameters including upper age and body mass index after approval from the multidisciplinary board. Also, left lobe grafts, grafts with various anatomical variations, and a low graft-to-recipient ratio can be considered in appropriate situations. ABO-incompatible LT and donor swapping at times may help in expanding the LLDs pool. Similarly, legislation is needed to allow live non-blood-related donors for organ donations. Finally, community education and awareness through various social media flat forms are needed to promote deceased organ donation.

Several surgical strategies, including split donor transplantation and living donor transplantation, have been used to increase the donor liver pool. This report focuses on the effects of whole, split, and LDLT on recipient outcomes.

We retrospectively analyzed the records of all patients with biliary atresia at Tianjin First Central Hospital between April 2013 and December 2019.

A total of 882 patients were included and divided into three groups by graft type, with 198 in the whole-liver-transplantation group, 78 in the split liver transplantation group, and 606 in the LDLT group. The median follow-up time was 39 months, patient survival rates of three groups were 94.4%, 88.5%, and 95.0%, respectively, and graft survival rates were 90.2%, 83.3%, and 94.7%, respectively. We divided the split liver transplantation group into two subgroups according to the donor's age, and patient survival rates exhibited a significant difference only in the group whose donor age was over 45 years. The postoperative complication rates were significantly higher with respect to hepatic artery thrombosis, portal stenosis, and AR; and lower in hepatic venous stenosis, PTLDs, CMV virus, and EBV infection in the WLT group. Our multivariate model showed that donor age ≥45 years, RBC transfusion, pneumonia, and HAT were the independent predictors of allograft loss.

The survival of split liver transplantation group was slightly lower. The types of complications are different from different graft types. Therefore, postoperative monitoring and treatment need to be adjusted according to the different graft types used.

In spite of substantial technical improvements and conceptual revolutions in advanced liver surgery, there are still straitened circumstances that pose difficulties for in-situ liver resections. Ex-vivo liver resection and autotransplantation (ELRA) is a hybrid technique combining experiences from conventional liver surgery and liver transplantation. This technique is becoming more comprehensive and popular among leading centers recently.

Short-term and long-term outcomes are now the focus of the technique after more than a decade of cumulative progress and technical evolution. As the 5-year survival nowadays reaches over 80%, this technique is believed to be beneficial for advanced tumors. In recent years, ELRA has been applied by more centers on larger scales, and the learning curve was set at 53 cases. Progresses in disease selection, surgical indications, individualized outflow reconstruction, or autograft implantation, management of co-morbidities (e.g., Budd-Chiari syndrome, caval and/or neighboring organ involvements, obstructive jaundice) propelled the development of the technique.

This hybrid liver surgery will benefit for carefully selected patients presented with advanced benign diseases and well-differentiated malignancies.

Liver transplantation (LT) for children results in excellent short- and long-term patient and graft survival. LT is a lifesaving procedure in children with acute or chronic liver disease, hepatic tumors, and select genetic metabolic diseases in which it can significantly improve quality of life. In this article, the authors discuss the unique aspects of pediatric LT, including the indications, appropriate patient selection and evaluation, allocation of organs, transplant surgery including the use of variant grafts, posttransplant care including immunosuppression management, prognosis, and transition of care.

Pediatric patients constitute an important group within the general transplant population, given the opportunity to significantly extend their lives with successful transplantation. Children have historically received special consideration under the various abdominal solid organ allocation algorithms, but matching patients with size and weight restrictions with appropriate donors remains an ongoing issue. Here, we describe the historical trends in pediatric organ allocation policies for liver, kidney, intestine, and pancreas transplantation. We also review recent changes to these allocation policies, with particular attention to recent amendments to geographical prioritization, with the dissolution of donor service areas and United Network for Organ Sharing (UNOS) regions and the subsequent creation of acuity circles.

Outcomes of left lateral segment (LLS) grafts in pediatric recipients were compared between living (LD-LLS) and deceased donor (DD-LLS) grafts.

195 LLS grafts (99DD-LLS-96LD-LLS) were analyzed with a median follow-up of 9.1years. The primary endpoints were overall patient/graft survival.

LD-LLS grafts were younger (0.9vs.1.4years, p = 0.039), more likely to have a fulminant liver failure (17.9%vs.5.3%,p = 0.002), less likely to have a metabolic disorder (6.3%vs.25.5%,p = 0.002), and less likely to be undergoing retransplantation (5.3% vs.16.2%,p = 0.015). There was a trend toward decreased hepatic artery thrombosis in LD-LLS grafts (6.6% vs. 15.5%,p = 0.054). No differences in the overall biliary complications occurred. The LD-LLS group had prolonged survival compared to the DD-LLS group with 10-year survival rates of 81%, and 74% (p = 0.005), respectively. LD-LLS grafts had longer graft survival compared to DD-LLS grafts (10-year graft survival 85%vs.67%,p = 0.005). Recipient age >1year (HR 2.39,p = 0.026), aortic reconstruction (HR 2.12,p = 0.046) and vascular complication (HR 3.12,p < 0.001) were independent predictors of poor patient survival. Non-biliary liver disease (HR 2.17,p = 0.015), DD-LLS (HR 2.06,p = 0.034) and vascular complication (HR 4.61,p < 0.001) were independent predictors of poor graft survival.

The use of SLT remains a viable option with excellent long-term outcomes. We show improved graft and patient survival with living donor grafts.