Organ transplantation, particularly pediatric liver transplantation (LT), has transformed medical practice over the past six decades, providing life-saving interventions for children with end-stage liver disease. This review demonstrated the historical milestones of pediatric organ transplantation, emphasizing Japan's contributions, mainly through the National Center for Child Health and Development. While early transplantation efforts in the 1950s and 1960s faced significant challenges, breakthroughs in preservation methods, immunosuppressive therapies, surgical techniques, and innovations such as living donor LT in Asia have greatly improved success rates. Japan's pediatric LT landscape is distinct, primarily due to its reliance on living donor LT, shaped by cultural and religious influences that have traditionally restricted deceased donor organ donation. This review manuscript discusses Japan's pioneering role in expanding the indications for pediatric LT to include rare conditions such as inherited metabolic disorders and hepatoblastoma. It highlights recent innovations such as hyper-reduced lateral segment grafts, machine perfusion, and minimally invasive surgery that have further improved outcomes. International collaboration has facilitated the sharing of expertise, advancing pediatric live transplantation practice worldwide. Despite these achievements, challenges remain, particularly in light of Japan's declining birth rate, which threatens the sustainability of pediatric transplant services. This review emphasizes the need for centralized transplant facilities, greater awareness of brain-dead organ donation, and continued medical advances to ensure that pediatric LT remains a viable, life-saving option for future generations.

Acute liver failure (ALF) caused by hepatic vascular injury during cholecystectomy is a rare but serious indication of liver transplantation (LT). We present a case of acute liver failure secondary to portal vein, hepatic artery, and common bile duct injury during laparoscopic cholecystectomy, requiring a same-day emergency living donor liver transplantation (LDLT). A 57-year-old man underwent elective laparoscopic cholecystectomy at an external facility. During the operation, uncontrolled bleeding from the liver hilum led to conversion to open surgery. Despite attempts to control the bleeding with sutures, the patient developed abnormal liver enzymes postoperatively. A computed tomography scan revealed necrosis of the right liver lobe and hypoplasia of the left lobe, leading to the patient to be transferred to our center. Upon admission, the patient was found to have encephalopathy, coagulopathy, hypotension, and oliguria, with elevated transaminase levels. Based on these findings, an emergency LT was deemed necessary. Due to the unavailability of a cadaveric organ, the patient's daughter was prepared as a living donor. Exploratory laparotomy revealed a necrotic right liver lobe, atrophic left lobe, transection of the right hepatic artery and common bile duct, and a thrombosed right portal vein. The patient successfully underwent LDLT from his daughter within 24 hours. At the seventh-month follow-up, he had no complications. Hepatic vascular injury during laparoscopic cholecystectomy can lead to ALF, which carries a high mortality risk. In such cases, LDLT may be a life-saving strategy. Early referral of a patient with ALF to a transplant center is life-saving.

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.

A strategic vision toward global convergence in transplantation must encourage and remove barriers to living organ donation and transplantation. Here, we discuss deliberations of a working group of the 2023 Santander Summit charged with formulating recommendations for the safe expansion of living donor kidney transplantation and living donor liver transplantation worldwide. Living donor kidney transplantation has grown to be the preferred treatment for advanced kidney failure. Living donor liver transplantation emerged more recently as a strategy to reduce waitlist mortality, with adoption influenced by cultural factors, regional policies, clinical team experience, and the maturity of regional deceased donor transplant systems. Barriers to living donor transplantation span domains of education, infrastructure, risk assessment/risk communication, and financial burden to donors. Paired donor exchange is a growing option for overcoming incompatibilities to transplantation but is variably used across and within countries. Effectively expanding access to living donor transplantation requires multifaceted strategies, including improved education and outreach, and measures to enhance efficiency, transparency, and shared decision making in donor candidate evaluation. Efforts toward global dissemination and vigilant oversight of best practices and international standards for the assessment, informed consent, approval, and monitoring of living donors are needed. Fostering greater participation in paired exchange requires eliminating disincentives and logistical obstacles for transplant programs and patients, and establishing an ethical and legal framework grounded in World Health Organization Guiding Principles. Sharing of best practices from successful countries and programs to jurisdictions with emerging practices is vital to safely expand the practice of living donation worldwide and bring the field together globally.

Acute post-surgical pain is a common concern for patients undergoing living donor hepatectomy (LDH), potentially leading to unfavorable outcomes if not treated adequately. This study aimed to evaluate the impact of the transition of surgical techniques from open and laparoscopic to robot-assisted minimally invasive surgical (MIS) approach, and the different types of graft resection, including right, left, and left lateral partial lobectomy (LL), on analgesia requirements during the first two postoperative days.

A single-center retrospective electronic chart review of all patients who underwent LDH procedures between 2018 and 2020 was performed.

Patients underwent LDH procedure (n = 414) through open (n = 93, 22%), laparoscopic (n = 68, 16%), or robot-assisted MIS (n = 253, 61%) approaches; and had right lobectomy (n = 215, 52%), left lobectomy (n = 121, 29%), or LL (n = 78, 19%). Postoperatively within the first 48 h, the pain reported on a 3-point Visual Analogue Scale (VAS), was mild 77%, moderate 21%, or severe only 2%. The laparoscopic approach and LL resection were associated with higher pain scores, whereas the robotic approach was the least painful overall.

Robot-assisted MIS approach for LDH procedure resulted in lower acute pain scores when compared with other surgical approaches, obviating the need for intravenous (IV) patient-controlled analgesia (PCA).

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.

Living donor liver transplantation (LDLT) has been proposed in many countries to reduce organ shortage. While the early postoperative outcomes have been well investigated, little is known about the long-term follow-up of the living donors. We, therefore, designed a systematic review of the literature to explore long-term complications and quality of life among living donors. We searched MEDLINE and EMBASE registries for studies published since 2013 that specifically addressed long-term follow-up following living-donor liver donation, concerning both physical and psychological aspects. Publications with a follow-up shorter than 1 year or that did not clearly state the timing of outcomes were excluded. A total of 2505 papers were initially identified. After a thorough selection, 17 articles were identified as meeting the eligibility criteria. The selected articles were mostly from North America and Eastern countries. Follow-up periods ranged from 1 to 11.5 years. The most common complications were incision site discomfort (13.2-38.8%) and psychiatric disorders (1-22%). Biliary strictures occurred in 1-14% of cases. Minimally invasive donor hepatectomy could improve quality of life, but long-term data are limited. About 30 years after the first reported LDLT, little has been published about the long-term follow-up of the living donors. Different factors may contribute to this gap, including the fact that, as healthy individuals, living donors are frequently lost during mid-term follow-up. Although the reported studies seem to confirm long-term donor safety, further research is needed to address the real-life long-term impact of this procedure.

Background: Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction technique" to correct the narrowed remnant portal vein just or late after right lobe living donor hepatectomy. Methods: Demographic and clinical data of 12 living liver donors with narrowed remnant portal veins and treated with the "elbow patch reconstruction technique" were prospectively collected and retrospectively evaluated. Anatomic variation of the portal vein was defined in accordance with the Nakamura classification; six of the living liver donors had type A, three had type B, and the remaining three had type C. In eight of the living liver donors with a narrowed remnant portal vein, diagnosis was detected by intraoperative Doppler ultrasonography and visual inspection by experienced transplant surgeons in the living donor hepatectomy procedure. In the remaining four living liver donors, diagnosis was performed postoperatively when elevation of liver enzymes was noticed during the routine liver function test and Doppler US. The diagnosis was confirmed by multidetector computed tomography. Results: Data from nine males and three females aged 18 to 54 years were analyzed. All of the living liver donors were followed up for a median of 1710 days (min-max: 1178-4447 days; IQR: 1516 days), and none of the living liver donors had any structural or functional complications in the portal vein. Conclusions: Narrowing remnant portal veins are rare, but they are a life-threatening complication in living liver donors, and this condition requires urgent management. Image guided interventions and narrowed segment resection with end-to-end anastomosis using a vascular graft carried a potential risk for thrombosis and restenosis. To avoid these complications, we shared a technique named "elbow patch reconstruction technique". This technique can be very effective in relieving the narrowing of the remnant portal vein after right lobe living donor hepatectomy.

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.

Living Donor Liver Transplantation (LDLT) has seen great advancements since its inception in 1988. Herein, the nuances of LDLT are discussed spanning from donor evaluation to the recipient operation. Special attention is given to donor anatomy and graft optimization techniques in the recipient.

ND2 in Ho Chi Minh City is currently the only public center that performs PLT in Southern Vietnam. In 2005, the first PLT was successfully performed, with support from Belgian experts. This study reviews the implementation of PLT at our center and evaluates the results and challenges.

Implementation of PLT at ND2 required medico-surgical team building and extensive improvement of hospital facilities. Records of 13 transplant recipients from 2005 to 2020 were studied retrospectively. Short- and long-term complications, as well as the survival rates, were reported.

The mean follow-up time was 8.3 ± 5.7 years. Surgical complications included one case of hepatic artery thrombosis that was successfully repaired, one case of colon perforation resulting in death from sepsis, and two cases of bile leak that were drained surgically. PTLD was observed in five patients, of whom three died. There were no cases of retransplantation. The 1-year, 5-year, and 10-year patient survival rates were 84.6%, 69.2%, and 69.2%, respectively. There were no cases of complication or death among the donors.

Living-donor PLT was developed at ND2 for providing a life-saving treatment to children with end-stage liver disease. Early surgical complication rate was low, and the patient survival rate was satisfactory at 1 year. Long-term survival decreased considerably due to PTLD. Future challenges include surgical autonomy and improvement of long-term medical follow-up with a particular emphasis on prevention and management of Epstein-Barr virus-related disease.

Background: Under the circumstance of the increasing waiting list for liver transplantation, living donor liver transplantation (LDLT) can alleviate the shortage of liver donors to some extent. However, how to reduce both donor and graft ischemia-reperfusion injury (IRI) is still an unsolved problem in LDLT. Hypoxia-induced transcription factor 1 (HIF1) activation is considered an important mechanism of cellular adaptation to hypoxia, and early activation of HIF1 may be a new way to alleviate liver IRI. Therefore, we aimed to investigate the impact of the HIF1 stabilizer dimethyloxalylglycine (DMOG) on IRI and the survival rate of donors and recipients of rat LDLT. Methods: Seventy percent partial liver resection and 30% partial liver transplantation were used to simulate donor and recipient of clinical LDLT. Rats were treated with DMOG (40 mg/kg) or with an equivalent amount of saline. The expression of HIF1 and downstream targets was analyzed after 2 h of reperfusion. Liver function and histopathology, apoptosis and oxidative stress levels were detected 6 h after reperfusion. At the same time, the 7-day survival rate of rats was calculated. Results: DMOG pretreatment significantly reduced IR-induced injury in the donor and recipient, which was manifested by reducing liver function damage and promoting tissue recovery. Meanwhile, compared with the untreated group, the oxidative stress level and the cell apoptosis rate were decreased in the group pretreated with DMOG. In addition, the transcription and expression of HIF1 target genes in the DMOG group were significantly enhanced. Remarkably, DMOG also increased the survival rate of the recipient. Conclusion: This study provides the first evidence that DMOG pretreatment of donors significantly alleviates liver IRI in both donors and recipients and increases the survival rate of recipients in LDLT. Therefore, DMOG may be a promising strategy for improving LDLT in the future.

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.

Living donor liver transplantation (LDLT) has become a popular treatment option because some countries lack a deceased organ program and the growing demand for liver transplants. Although postoperative outcomes are similar to deceased donor liver transplants, there is still an element of risk to the donor. The Clavien-Dindo classification system has been used to standardize reporting across different institutions and surgeons to categorize surgical outcomes.

Between January 1, 2022, and December 31, 2022, 207 living donors underwent hepatectomies at our center. All donors underwent a 3-step process of mandatory screening. Postsurgical complications were classified using the Clavien-Dindo classification.

A total of 207 donor hepatectomies for LDLT were performed during our study period. Most donors (92.8%) were aged between 18 and 39 years. The most common type of graft used was a right lobe without the middle hepatic vein (82.6%). Most donors (91.7%) experienced an intraoperative blood loss of ≤500 mL. A total of 140 patients had an ordinary postoperative course. Grade 1 complications were observed in 16.9%, grade 2 in 12.1%, and grade 3 in 3.4% of the remaining patients. No grade 4 or grade 5 (patient death) complications were observed in this cohort.

Living donor liver transplantation remains the most practiced liver transplant surgery in Pakistan. Our findings highlight the safety of the LDLT program with minimal risk of significant complications. The study also underscores the importance of careful screening and monitoring of living donors and the need for standardized reporting of surgical outcomes using the Clavien-Dindo classification system.

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.

With an incidence exceeding 30%, biliary complications after pediatric liver transplantation remain a great challenge. In addition, the database includes numerous controversial papers about the safety of duct-to-duct anastomosis compared to Reux-en-Y hepaticojejunostomy for pediatric living donor liver transplantation (LDLT). We aim to compare the two techniques in pediatric LDLT by conducting a systematic review and meta-analysis. PUBMED, Web of Science, Scopus, and Cochrane Library were searched for eligible studies from 1989 to October 2022. According to our eligibility criteria, seven articles (561 pediatric LDLT) were included in our study. On one hand, DD anastomosis is associated with a higher rate of biliary stricture in comparison to RYHJ (OR: 2.47, 95% CI = 1.20-5.09, P = 0.01; I2 = 12%). On the other hand, the incidence of cholangitis was higher in RYHJ (OR: 0.10 95% CI = 0.01- 0.84, P = 0.03; I2 = 0%). However, there was no significant difference in the overall incidence of complications, leakage and mortality between the two groups (overall incidence of complication OR: 1.12, 95% CI = 0.34-3.68, P = 0.86; I2 = 62%), (Leakage OR: 2.22, 95% CI = 0.79-6.23, P = 0.13; I2 = 18%) and (Mortality OR: 2.53, 95% CI = 0.61-10.57, P = 0.30; I2 = 0%). In conclusion, with a lower incidence of cholangitis, an equal overall incidence of biliary complication, and the possibility of RY conversion in case of stricture, DD anastomosis offers a feasible, safe, and more physiological alternative to RYHJ for pediatric LDLT.

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."

This review provides an overview of the current status of Living Donor Liver Transplant (LDLT). It discusses the impact of LDLT on waitlist and post-transplantation outcomes, highlighting the technical challenges and unique advantages of LDLT.

Recent findings show that LDLT offers several theoretical advantages over deceased donor liver transplant, including shorter wait times, better graft quality, and improved post-transplant outcomes. Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are emerging as the leading indications for adult LDLT in the US. LDLT demonstrates comparable or better overall survival rates and organ-specific outcomes compared to deceased donor transplants. However, challenges exist, including donor and recipient risks such as biliary complications and small-for-size syndrome. Ongoing research focuses on refining surgical techniques, exploring minimally invasive approaches, utilizing predetermined donors to modulate the recipient's immune system, and ensuring ethical practices. LDLT is a valuable solution for patients with end-stage liver failure or disorders requiring transplantation. It offers advantages such as shorter wait times as well as improved waitlist and post-transplant outcomes. Continued research and advancements in LDLT will benefit patients in need of liver transplantation.

Liver transplant is the definitive treatment of end-stage liver disease and early hepatocellular carcinoma. The number of liver transplant surgeries done is highly affected by the number and availability of deceased donor organs. Living donor liver transplantation has emerged as an alternative source of donors, increasing the availability of organs for transplant. Many factors must be considered when choosing living donor candidates to maintain a high level of donor safety and organ survival. To that end, potential donors undergo a rigorous pre-donation workup.

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.

The outcomes of liver transplantation (LT) from different grafts have been studied individually and in combination, but the reports were conflicting with some researchers finding no difference in both short-term and long-term outcomes between the deceased donor split LT (DD-SLT) and living donor LT (LDLT).

To compare the outcomes of DD-SLT and LDLT we performed this systematic review and meta-analysis.

This systematic review was performed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The following databases were searched for articles comparing outcomes of DD-SLT and LDLT: PubMed; Google Scholar; Embase; Cochrane Central Register of Controlled Trials; the Cochrane Database of Systematic Reviews; and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The search terms used were: "liver transplantation;" "liver transplant;" "split liver transplant;" "living donor liver transplant;" "partial liver transplant;" "partial liver graft;" "ex vivo splitting;" and "in vivo splitting."

Ten studies were included for the data synthesis and meta-analysis. There were a total of 4836 patients. The overall survival rate at 1 year, 3 years and 5 years was superior in patients that received LDLT compared to DD-SLT. At 1 year, the hazard ratios was 1.44 (95% confidence interval: 1.16-1.78; P = 0.001). The graft survival rate at 3 years and 5 years was superior in the LDLT group (3 year hazard ratio: 1.28; 95% confidence interval: 1.01-1.63; P = 0.04).

This meta-analysis showed that LDLT has better graft survival and overall survival when compared to DD-SLT.

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.

Pediatric liver transplantation is an important modality for treating biliary atresia. The overall survival (OS) rate of pediatric liver transplantation has significantly improved compared with that of 20 years ago, but it is still unsatisfactory. The anesthesia strategy of maintaining low central venous pressure (CVP) has shown a positive effect on prognosis in adult liver transplantation. However, this relationship remains unclear in pediatric liver transplantation. Thus, this study was conducted to review the data of pediatric living-donor liver transplantation to analyze the associations of different CVP levels with the prognosis of recipients.

This was a retrospective study and the patients were divided into two groups according to CVP levels after abdominal closure: low CVP (LCVP) (≤ 10 cmH2O, n = 470) and high CVP (HCVP) (> 10 cmH2O, n = 242). The primary outcome measured in the study was the overall survival rate. The secondary outcomes included the duration of mechanical ventilation in the intensive care unit (ICU), length of stay in the ICU, and postoperative stay in the hospital. Patient demographic and perioperative data were collected and compared between the two groups. Kaplan-Meier curves were constructed to determine the associations of different CVP levels with the survival rate.

In the study, 712 patients, including 470 in the LCVP group and 242 in the HCVP group, were enrolled. After propensity score matching, 212 pairs remained in the group. The LCVP group showed a higher overall survival rate than the HCVP group in the Kaplan-Meier curves and multivariate Cox regression analyses (P = 0.018), and the HCVP group had a hazard ratio of 2.445 (95% confidence interval, 1.163-5.140).

This study confirmed that a low-CVP level at the end of surgery is associated with improved overall survival and a shorter length of hospital stay.

Cholecystectomy is routinely performed during living donor hepatectomy both to see the structure of the biliary tract and to determine the demarcation line based on the biliary tract junction. This study aims to present the general histopathological features of the gallbladder specimen obtained from living liver donors (LLD).

Data from 2577 LLDs who underwent living donor hepatectomy (n = 2511) or aborted living donor hepatectomy (n = 66) in our Liver Transplantation Institute between September 2005 and June 2021 were analyzed retrospectively. Age, gender, macroscopic (length, diameter, and wall thickness), and microscopic (histopathological) features of the gallbladder of the LLDs were recorded for use in this study.

A total of 2493 LLDs (men: 1486, women: 1007) with a median age of 29 years (interquartile range [IQR]: 13) met the inclusion criteria in this study. The median length, width and wall thickness of the gallbladder specimens were measured as 70 mm (IQR: 20), 50 mm (IQR: 20), and 2 mm (IQR: 1), respectively. The most common histopathological findings are normal structure (2026; 81.3%), chronic cholecystitis (n = 446; 17.9%), adenomyomatosis (n = 9), and papillary hyperplasia (n = 6), respectively. The most common pathologic findings in the gallbladder lumen are cholesterolosis (n = 207; 0.4%), cholelithiasis (n = 53), cholesterol polyp (n = 31), and noncholesterol polyp (n = 19), respectively. Significant differences were detected between the male and female genders in terms of age (P < .001), height (P < .001), weight (P < .001), body mass index (P < .001), gallbladder width (P = .001), gallbladder length (P < .001), histopathological finding (content) (P < .001), and lymph node around the gallbladder (P = .015).

The results we obtained in this study are true gallbladder pathologies that can be detected in healthy people. In this study, it was shown that the diameter and size of the gallbladder were larger in men, whereas the incidence of cholesterolosis and cholelithiasis was higher in women.

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.

In this review, we describe the major milestones in the development of organ transplantation with a specific focus on hepatic transplantation. For many years, the barriers preventing successful organ transplantation in humans seemed insurmountable. Although advances in surgical technique provided the technical ability to perform organ transplantation, limited understanding of immunology prevented successful organ transplantation. The breakthrough to success was the result of several significant discoveries between 1950 and 1980 involving improved surgical techniques, the development of effective preservative solutions, and the suppression of cellular immunity to prevent graft rejection. After that, technical innovations and laboratory and clinical research developed rapidly. However, these advances alone could not have led to improved transplant outcomes without parallel advances in anesthesia and critical care. With increasing organ demand, it proved necessary to expand the donor pool, which has been achieved with the use of living donors, split grafts, extended criteria organs, and organs obtained through donation after cardiac death. Given this increased access to organs and organ resources, the number of transplantations performed every year has increased dramatically. New regulatory organizations and transplant societies provide critical oversight to ensure equitable organ distribution and a high standard of care and also perform outcome analyses. Establishing dedicated transplant anesthesia teams results in improved organ transplantation outcomes and provides a foundation for developing new standards for other subspecialties in anesthesiology, critical care, and medicine overall. Through a century of discovery, the success we enjoy at the present time is the result of the work of well-organized multidisciplinary teams following standardized protocols and thereby saving thousands of lives worldwide each year. With continuing innovation, the future is bright.

Liver transplantation (LT) is the only curative therapy for decompensated liver cirrhosis. For recipients of living donor LT (LDLT), restoration of liver function after transplantation is highly dependent on liver regenerative capacity, which requires large amounts of intracellular energy. Mitochondrial metabolism provides a stable supply of adenosine 5'-triphosphate (ATP) for liver regeneration. Mitophagy is a selective process in which damaged, non-functional mitochondria are degraded and replaced with new functional mitochondria. We investigated the relationship between expression of Syntaxin17 (STX17), a key protein in mitophagy regulation, in donor livers and graft survival.

We examined STX17 expression in grafts from 143 LDLT donors who underwent right lobe resection and investigated the relationship between STX17 expression and graft function. We investigated the correlations among STX17 expression, mitochondrial membrane potential and cell proliferation, using a STX17-knockdown hepatocyte cell line.

Recipients transplanted with low STX17-expression grafts had significantly lower graft survival rates than recipients transplanted with high STX17-expression grafts (88.9% vs. 100%, p < 0.01). Multivariate analysis showed that low STX17 expression (HR: 10.7, CI: 1.29-88.0, p < 0.05) and the absence of splenectomy (HR: 6.27, CI: 1.59-24.8, p < 0.01) were independent predictive factors for small-for-size graft syndrome, which is the severe complication in LDLT. In the vitro experiments, the percentage of depolarized damaged mitochondria was increased in the STX17-knockdown hepatocyte cell line, suggesting decreased mitophagy and ATP synthesis. Cell proliferation was significantly decreased in the STX17-knockdown hepatocyte cell line.

STX17 contributes to mitophagy and maintenance of mitochondrial function in hepatocytes and may be a predictor of graft dysfunction in LDLT patients.

The quality and size of liver grafts are critical factors that influence living-donor liver transplantation (LDLT) function and safety. However, the biomarkers used for predicting graft quality are lacking. In this study, we sought to identify unique graft quality markers, aside from donor age, by using the livers of non-human primates. Hepatic gene microarray expression data from young and elderly cynomolgus macaques revealed a total of 271 genes with significantly increased expression in the elderly. These candidate genes were then narrowed down to six through bioinformatics analyses. The expression patterns of these candidate genes in human donor liver tissues were subsequently examined. Importantly, we found that grafts exhibiting up-regulated expression of these six candidate genes were associated with an increased incidence of liver graft failure. Multivariable analysis further revealed that up-regulated expression of LRRN2 (encoding leucine-rich repeat protein, neuronal 2) in donor liver tissue served as an independent risk factor for graft failure (odds ratio 4.50, confidence interval 2.08-9.72). Stratification based on graft expression of LRRN2 and donor age was also significantly associated with 6-month graft survival rates. Conclusion: Up-regulated LRRN2 expression of liver graft is significantly correlated with graft failure in LDLT. In addition, combination of graft LRRN2 expression and donor age may represent a promising marker for predicting LDLT graft quality.

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.

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.

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.

Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long-term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline-in-Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta-analysis of unadjusted and adjusted odds and hazard ratios was performed using a random-effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1-year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53-0.88), 3-year (OR, 0.73; 95% CI, 0.61-0.89), 5-year (OR, 0.71; 95% CI, 0.57-0.89), and 10-year (OR, 0.42; 95% CI, 0.18-1.00) patient and 1-year (OR, 0.50; 95% CI, 0.35-0.70), 3-year (OR, 0.55; 95% CI, 0.37-0.83), 5-year (OR, 0.5; 95% CI, 0.32-0.76), and 10-year (OR, 0.26; 95% CI, 0.14-0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5-year patient survival (OR, 0.60; 95% CI, 0.38-0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well-described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

Pediatric liver transplant (PLT) activity has flourished over time although with limited expansion in the graft pool. The study aims to identify pre-transplant factors that predict post-transplant patient and graft survival in the PLT population.

Retrospective review of PLTs at a single tertiary transplant unit from 2000 to 2019. Univariate and multivariate analyses of pre-transplant factors were performed to identify predictors of patient and graft survival.

Two hundred and seventy-six patients received 320 PLTs. The most common cause of graft loss was hepatic artery thrombosis (n = 13, 29.6%). The most common cause of mortality was sepsis (n = 11, 29.7%). Univariate analysis showed that the following variables had a significant (p < .05) impact on patient survival: recipient age, weight, height, graft type (technical variant graft), transplant category (acute liver failure), the era of transplant, and invasive ventilation. The following variables had a significant (p < .05) impact on graft survival: recipient age, weight, height, transplant category (acute liver failure), and the era of transplant. Multivariate analysis precluded the era of transplant as the only significant factor for patient survival; patients transplanted after 2005 had significantly higher patient survival. No independent factor predicting graft survival was identified. For children transplanted after 2005, the only factor that predicted patient survival was pre-transplant invasive ventilation.

Our study suggests that the learning curve and pre-transplant invasive ventilation in the recipient have a significant impact on patient survival. The traditional view of worse outcomes of smaller PLT candidates should be changed.

Although living donor liver transplantation (LDLT) is the standard treatment option for patients with end-stage liver disease, it always entails ethical concerns about the risk of living donors. Recent studies have reported a correlation between sarcopenia and surgical prognosis in recipients. However, there are few studies of donor sarcopenia and the surgical prognosis of donors. This study investigated the association between sarcopenia and postoperative acute kidney injury in liver donors.

This retrospective study analysed 2892 donors who underwent donor hepatectomy for LDLT between January 2008 and January 2018. Sarcopenia was classified into pre-sarcopenia and severe sarcopenia, which were determined to be -1 standard deviation (SD), and -2 SD from the mean baseline of the skeletal muscle index, respectively. Multivariate regression analysis was performed to evaluate the association between donor sarcopenia and postoperative AKI. Additionally, we assessed the association between donor sarcopenia and delayed recovery of liver function (DRHF).

In the multivariate analysis, donor sarcopenia was significantly associated a higher incidence of postoperative AKI (adjusted odds ratio [OR]: 2.65, 95% confidence interval [CI]: 1.15-6.11, P = .022 in pre-sarcopenia, OR: 5.59, 95% CI: 1.11-28.15, P = .037 in severe sarcopenia, respectively). Additionally, hypertension and synthetic colloid use were significantly associated with postoperative AKI. In the multivariate analysis, risk factors of DRHF were male gender, indocyanine green retention rate at 15 minutes, and graft type, however, donor sarcopenia was not a risk factor.

Donor sarcopenia is associated with postoperative AKI following donor hepatectomy.