Pediatric Liver Transplantation Research Articles

Unlocking the Promise of Liver Perfusion Technologies for Pediatric Transplantation: A State-of-the-Art Review.

Outcomes after pediatric liver transplantation are generally excellent, but the limited avavailability of suitable, size-matched liver allografts remains a significant barrier. Machine perfusion technology has emerged as a promising approach to expand the donor pool, enabling the use of less ideal whole liver grafts, such as livers donated after circulatory death, and enhancing the execution of split liver transplantation. This review examines the application of machine perfusion in pediatric liver transplantation, focusing on two primary techniques: hypothermic oxygentaed perfusion and normothermic machine perfusion. These methods optimize storage, resuscitation, and assessment of liver grafts before transplantation, potentially expanding the range of usable donor organs. The use of machine perfusion allows for the consideration of suboptimal donor livers and facilitates split liver transplantation, both of which could increase organ availability for pediatric patients. Implementation of machine perfusion could also help reduce waiting list mortality by enabling the safe use of a broader spectrum of donor organs. Adoption of machine perfusion in pediatric liver transplantation will require collaborative, multidisciplinary efforts across transplant centers. By fostering cooperative learning and sharing resources. the integration of machine perfusion into clinical practice has the potential to reduce mortality among children awaiting liver transplantation.

Retrospective Cohort Study of Associated Factors for Intestinal Complications in Pediatric Liver Transplantation.

Intestinal complications (IC) represent serious adverse events after liver transplantation (LT), however limited research has been conducted in pediatric cohorts. This study aims to describe IC after pediatric LT and to identify associated factors. Retrospective review of 153 patients having undergone LT, aged 0-18 years, treated in the Swiss Pediatric Liver Center in Geneva. Pre-, per- and postoperative data were analyzed. IC were defined as pathologies or lesions directly associated with LT and attributable to the surgical procedure. 16/153 (11%) patients developed IC: 10/16 mechanical obstructions, 4/16 intestinal perforations and 2/16 sub-mesocolic abscesses. IC patients had a significantly lower Body Mass Index (BMI) (15.5 vs. 16.4, p = 0.019). Children with IC had significantly higher incidence of previous Kasai hepatoportoenterostomy associated with Ladd procedure (13% vs. 2%, p = 0.055), a history of intraoperative iatrogenic intestinal perforation(s) (31% vs. 5%, p = 0.003) and prolonged LT surgery duration (536 vs. 415 min, p = 0.007). Significantly more children with IC had received basiliximab (69% vs. 40%, p = 0.048). Patients with IC exhibited a higher incidence of post-LT sub-occlusions (p < 0.001) and an increased requirement for post-LT parenteral nutrition (p = 0.027). Additionally, IC patients underwent significantly more reoperations (p < 0.001). One in 10 children post-LT experiences IC, which are associated with significant morbidity. Pre-LT nutritional status appears as an associated factor with IC, along with the necessity for adhesiolysis during LT, often leading to prolonged operative time. These associated factors should alert medical teams to promote early IC diagnosis in patients after LT.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.

Pediatric liver transplant for acute liver failure: Defining the standard nutrition and clinical evolution: An observational study.

Pediatric acute liver failure (PALF) is a clinical diagnosis in which previously asymptomatic children exhibit a rapid loss of liver function. To describe the clinical and nutrition conditions at admission and during hospitalization in patients with PALF who underwent liver transplantation (LT) at a referral center and establish a possible association between nutrition status and prognosis in this population. A prospective study was conducted on children underwent LT because of PALF. Nutrition assessment was performed at admission and repeated weekly until hospital discharge, and their relationships with clinical outcomes were tested. The study population consisted of 23 patients with a median age of 60 months and, in most cases, the etiology of acute liver failure (ALF) was indeterminate (69.6%). The majority of the patients were well nourished according to the z score body mass index-for-age (82.6%) and z arm circumference-for-age (zAC/A) (82.6%). A decline in nutrition status was observed in 47.6% of the patients, as indicated by a decrease in zAC. Clinical and nutrition improvement was demonstrated by the progressive increase in zAC, serum albumin levels, and phase angle (PA) values and by the reduction in C-reactive protein levels. There was no statistically significant relationship between nutrition status and clinical outcomes. Most children and adolescents with ALF presented adequate nutrition status at the time of LT, and some patients worsened their nutrition status during hospitalization, suggesting that post-LT is a period of high nutrition risk, and early nutrition therapy (NT) must be a priority in these patients.

Challenges for pediatric liver transplantation in mainland China: Where we are and where to go. Reflections from worldwide largest pediatric liver transplantation program

Challenges for pediatric liver transplantation in mainland China: Where we are and where to go. Reflections from worldwide largest pediatric liver transplantation program

In memoriam: Sir Roy Calne (1930-2024) - A life in surgery and impact on paediatric liver transplantation in Singapore.

In memoriam: Sir Roy Calne (1930-2024) - A life in surgery and impact on paediatric liver transplantation in Singapore.

Perioperative Complications After Pediatric Liver Transplantation-A Retrospective Analysis of 421 Cases.

Due to the low incidence of pediatric liver transplantations, short- and long-term data regarding their outcome, details on early postoperative complications and their risk factors are under-represented in the literature. We retrospectively reviewed 1645 LTx performed at Hannover Medical School between January 2005 and December 2021. Of these, 421 transplantations were performed in 405 pediatric recipients. Univariate and multivariate binary logistic regressions were performed to identify independent risk factors for the onset of selected perioperative complications requiring intervention within the first 30 days following transplantation and their influence on graft and patient survival. Pleural effusions represent the most common postoperative complication observed in 49.4% (n = 208) of cases, followed by vascular complications in 22.6% (n = 95) and biliary complications in 20.0% (n = 84) of cases. Donor age (OR: 1.019; p = 0.010) and recipient age between 3 and 12 years (OR: 1.849; p = 0.008) were identified as independent risk factors for the onset of pleural effusions. Retransplantations within the first year after LTx were necessary in 11.4% of all cases (n = 48). Twenty (4.8%) patients died within the first year after LTx. Pleural effusions requiring postoperative intervention were observed in approximately half of the pediatric recipients. Therefore, the preemptive intraoperative placement of a chest drain under sterile conditions and general anesthesia should be considered. Our data further indicate that a two-stage procedure for biliary reconstruction may be the preferred procedure in patients at risk of early bile duct complications and retransplantation within the first year.

Neighborhood-Level Deprivation Impacts Graft and Patient Outcomes Among Pediatric Liver Transplant Recipients.

The impact of social determinants of health (SDOH) on pediatric liver transplant outcomes has not been extensively investigated. The purpose of this study was to examine the effect of neighborhood-level deprivation on graft and patient survival among pediatric liver transplant recipients. This is a single-center observational study among children who received a primary liver transplant from March 1996 to March 2023. The Childhood Opportunity Index (COI) score was used to measure the degree of neighborhood deprivation. A total of 252 children were included, half (52.8%) were female and the majority were non-Hispanic White (71%). Half (53.6%) of the children had private insurance, and the median COI score was 64. A total of 28 children were transplanted from a very low-to-low COI area. Children in very low-to-low COI areas had worse patient (HR = 4.90, 95% CI = 1.41-17.04, p = 0.01) and graft (HR = 3.41, 95% CI = 1.19-9.75, p = 0.02) survival outcomes compared to children in moderate-to-very high areas when adjusting for clinical characteristics. COI score remained a significant predictor of graft survival after adjusting for race and insurance type (HR = 3.41, 95% CI = 1.12-10.40, p = 0.03). Pediatric liver transplant recipients from very low-to-low COI score areas have worse graft outcomes when accounting for clinical factors, race/ethnicity, and insurance status. Future research should investigate the impact of multiple, intersecting SDOH factors, rather than solely a collection of isolated variables.

Advances and challenges in pediatric liver transplantation: Global perspectives and the Japanese experience

Advances and challenges in pediatric liver transplantation: Global perspectives and the Japanese experience

Are the differences really different? understanding the role of induction immunosuppression on pediatric liver transplant outcomes.

Are the differences really different? understanding the role of induction immunosuppression on pediatric liver transplant outcomes.

Does the introduction of acuity circle policy change split liver transplantation practice?

With the Acuity Circles (AC) policy aiming to reduce disparities in liver transplantation (LT) access, the allocation of high-quality grafts has shifted, potentially affecting the use and outcomes of split LT. Data from the United Network for Organ Sharing (UNOS) database (February 4, 2016, to February 3, 2024) were analyzed, including 1,470 candidates who underwent deceased donor split LT, with 681 adult and 789 pediatric cases. The study periods were divided into pre-AC (February 4, 2016, to February 3, 2020) and post-AC (February 4, 2020, to February 3, 2024). The study assessed changes in split LT volumes and examined the impact of center practices. Both adult and pediatric split LTs decreased in the initial three years post-policy change, followed by an increase in the final year, with an overall 11.9% and 13.9% decrease between the eras. Adult female split LT cases remained consistent, ensuring access for smaller recipients. High-quality "splittable" livers were increasingly allocated to high MELD patients (MELD-Na ≥30). Despite the overall decrease in case volume, adult split LT volume increased in newly active LDLT centers, with six centers increasing LDLT volume by over 50.0%. Pediatric split LT volumes decreased despite additional priorities for pediatric candidates. The number of split LTs decreased in the initial period after the AC policy introduction, but there was a consistent need for small female candidates. In the adult population, LDLT and split LT demonstrated a synergistic effect in boosting center transplant volumes, potentially improving access for female candidates who need small grafts.

Prediction of Whole Liver Graft Weight Based on Biometric Variables in Paediatric and Adult Liver Donors.

In paediatric liver transplantation, donor-recipient compatibility depends on graft size. We explored whether the graft weight can be predicted using the donor's biometric parameters. We used seven easily available biometric variables in 142 anonymised paediatric and adult donors, with data collected between 2016 and 2022. The whole or partial liver was transplanted in our hospital from these donors. We identified the variables that had the strongest correlation to our response variable: whole liver graft weight. In child donors, we determined two linear models: using donor weight and height on the one hand and using donor weight and right liver span on the other hand. Both models had a coefficient of determination R2 = 0.86 and p-value < 10-5. We also determined two models in adult donors using donor weight and height (R2 = 0.33, p < 10-4) and donor weight and sternal height (R2 = 0.38, p < 10-4). The models proved valid based on our external dataset of 245 patients from two institutions. In clinical practise, our models could provide rapidly accessible estimates to determine whole graft dimension compatibility in liver transplantation in children and adults. Determining similar models predicting the left lobe and lateral segment weight could prove invaluable in paediatric transplantation.

Effect of Age at Liver Transplant on Anxiety, Depression, and Quality of Life Among Adolescents.

Introduction: Life expectancy for pediatric liver transplant patients has increased over the past decade. Different stages of the transplant process can impact patients' quality of life (QOL) and create psychological and physical stressors. This study explored whether age at transplant affected adolescents' feelings of anxiety, depression, and QOL. Design: In this cross-sectional quantitative study, data were collected on 22 adolescent patients aged 13-18 who received a transplant at least 12 months before enrollment. This cohort was divided into 2 groups based on their age at transplant: Group 1 (0-5 years) and Group 2 (6-18 years). To assess transplant-related anxiety, depression, and QOL, participants completed 3 surveys: the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), and the Pediatric Quality of Life Inventory™ Transplant Module (PedsQL TM). Results: Group 1 experienced less anxiety and fewer problems based on GAD-7 scores but reported stronger feelings of depression based on PHQ-9 scores. Based on the PedsQL TM scale, Group 1 had higher mean scores compared to Group 2 across all components (mean difference range: 7.2- 27.3; Cohen's d range: 0.27 - 1.13). The largest difference between the 2 groups was observed on the PedsQL TM scale's How I Look (Group 1 mean 81.1 vs. Group 2 mean 53.8; Cohen's d: 1.13; P = 0.015), Conclusion: In this cohort, age at transplant affected adolescents' feelings of anxiety, depression, and QOL. Awareness of these findings can help clinicians screen for and address mental health issues.

Optimal transplant strategy of pediatric liver transplantation for fibropolycystic liver disease: Multicenter retrospective study in Japan.

To assess the preoperative disease characteristics and indications for living donor liver transplantation (LDLT), complications, patient survival, and prognosis after LDLT for fibropolycystic liver disease (FLD) in children. We undertook a cross-sectional survey of patients who underwent LDLT for FLD between January 2002 and December 2020. A total of 35 patients (22 male and 13 female individuals) with FLD were included in this study, of whom 19 (54.3%) had isolated congenital hepatic fibrosis and 16 (45.6%) had Caroli syndrome. Refractory gastrointestinal bleeding was the most frequent symptom related to the indication for LDLT, being found in 48.6% of our patients, followed by uncontrollable cholangitis and ascites. The median age at the time of LDLT was 8.1years old. Of the 27 patients presenting with renal involvement, 13 patients required kidney transplantation (KT). Overall, the renal function after LDLT decreased regardless of renal involvement; however, patients with renal involvement had a significantly lower estimated glomerular filtration rate than those without renal involvement throughout the course of this study (p<0.01). The 5-year overall patient survival rate was 97.1%. Two patients died with a median follow-up of 8.9years after LDLT; one died due to sepsis 2weeks after simultaneous liver-kidney transplantation and the other committed suicide 10years after LDLT. The prognosis of the pediatric patients who underwent LDLT for FLD was excellent. However, an individualized treatment approach based on the status of the renal function and liver disease is important, as a certain proportion of patients require KT.

Study of related factors to vascular complications after pediatric liver transplantation

Objective: To explore the related factors of vascular complications after liver transplantation in children. Methods: This is a retrospective case-series research. The clinical data of 89 pediatric liver transplant patients admitted to the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2016 to March 2024 were collected retrospectively. This study included 44 males and 45 females,aged from 4 months to 17 years. The ratio of graft to recipient weight was 0.6% to 7.7%. The primary diseases included 48 cases of biliary atresia and 41 cases of non-biliary atresia. The t-test, Wilcoxon rank sum test, χ2 test, and Fisher's exact probability method were used for data analysis. Multivariate Logistic regression was used to analyze the related factors of vascular complications. Results: All 89 children with liver transplantation completed surgery successfully. There were 8 cases of arterial complications after surgery, including 6 cases of hepatic artery thrombosis and 2 cases of hepatic artery stenosis. There were 16 cases of portal vein complications after surgery, including 9 cases of portal vein stenosis and 7 cases of portal vein thrombosis. The results of univariate analysis showed that the age of the recipient ≤1 year was the relevant factor for hepatic arterial complications(χ2=4.772,P=0.029). The age of the recipient ≤1 year, the age of the donor, the hepatic phase, and the time of cold ischemia were the relevant factors for the occurrence of portal vein complications(χ2=7.270,Z=388.500,Z=838.000, Z=594.500;all P<0.05). The results of multivariate analysis showed that age(≤1 year vs. >1 year) and duration of cold ischemia(every additional 1 hour) were independent related factors for portal vein complications after liver transplantation in children(both P<0.05). Conclusion: Children aged ≤1 year and with prolonged cold ischemia are more likely to develop portal vein complications after liver transplantation.

Awake prone positioning in an infant following living donor liver transplantation

BackgroundProne position has been proven to improve ventilation and oxygenation in infants. Currently, there are few reports of early prone position ventilation after pediatric liver transplantation. Here, we present our experience with prone position in an infant following living donor liver transplantation, in an attempt to improve oxygenation.Case presentationAn 8-month-old boy, 7.5 kg, experienced two failed extubations that presented with Type II respiratory failure due to dyspnea, potentially caused by consolidation and airway secretions. To prevent the third failure of extubation, prone position ventilation was implemented after the third extubation on the 11th postoperative day. Oxygenation increased after each prone position session with no signs of transplant liver ischemia or other adverse outcomes. Following two days of continuous prone position, airway secretions decreased, and the infant was discharged from the ICU. The third extubation procedure was successful.ConclusionsProne position ventilation may be effective in this infant without adverse events, indicating that early prone position is not absolutely contraindicated after pediatric liver transplantation. Therefore, more reasonable prone position strategies should be sought in infants undergoing liver transplantation.

Less is more: The use of a single biodegradable stenting to treat biliary anastomotic strictures in pediatric liver transplantation.

To report our experience of using biodegradable biliary stents for anastomotic biliary strictures in pediatric liver transplant patients. Analysis of a retrospective data collection from January 2014 to January 2023, including all pediatric liver transplant recipients in our center treated for anastomotic biliary strictures with biodegradable biliary stents (BBS). In phase 1 (2014-2019), there was an initial percutaneous transhepatic cholangiography (PTC) with anastomotic dilatation followed two weeks after by a second PTC with BBS insertion. In phase 2 (2019-2023), the BDS were placed shortly after anastomotic biliary strictures dilatation, requiring only one PTC. All patients were followed up with routine tests and ultrasound. Forty-six anastomotic biliary strictures were diagnosed in 43 pediatric liver transplant recipients with a median of 6.7 months post-liver transplantation (0.1-246.8 months). Eight out of 46 anastomotic biliary strictures (17.4%) treated with biodegradable biliary stents relapsed (median recurrence time: 6.5 months; 1.6-17.0 months). Four resolved with further BBS placement; only four needed surgical revision (8.7%) after a median follow-up time of 43.9 months (0.3-106.3). There were no differences in anastomotic biliary strictures recurrence rate, time between stent placement and recurrence, or the presence of cholangitis based on whether the BBS was deployed in one or two steps. Patients with end-to-end anastomosis had a higher anastomotic biliary strictures recurrence (or 10.8; 1.4-81.3, p=0.008) than those with bilioenteric anastomosis. The use of biodegradable stents stents could be good option for treating anastomotic biliary strictures in pediatric liver transplant patients, with our series showing a success rate of over 90% and an average follow-up of 43.9 months.

Cytomegalovirus prophylaxis in pediatric liver transplantation: A comparison of strategies across the Society of Pediatric Liver Transplantation consortium

Although cytomegalovirus (CMV) is a common complication after pediatric liver transplantation (PLT), the optimal method for CMV prevention is uncertain and lacks multicentered investigation. We compared the effectiveness of short (<120 days) vs long (>180 days) CMV primary antiviral prophylaxis to prevent CMV disease in PLT, through a prospective cohort study of primary PLT (aged <18 years) recipients enrolled in the Society of Pediatric Liver Transplantation registry from 2015 to 2019 with either donor or recipient CMV seropositivity. Participants were grouped into short or long prophylaxis based on their center’s practice and intended duration. In total, 199 PLT recipients were enrolled including 112 (56.3%) short and 87 (43.7%) long prophylaxis. End-organ disease was rare and similar between groups (2.7% and 1.1%; P = .45). CMV DNAemia and syndrome were more common in the short compared with those in long prophylaxis (26.8% vs 13.8%; P = .03; 18.8% vs 6.9%; P = .02). Neutropenia occurred more commonly with long prophylaxis (55.2% vs 16.1%; P < .001). Graft and patient survival were similar. Consideration of a short prophylaxis must weigh increased risk of CMV syndrome/DNAemia against medication burden and neutropenia of longer prophylaxis.

Hepatic artery stenosis after pediatric liver transplantation: The potential role of conservative management

AimThis study aimed to investigate the outcomes and effectiveness of various treatment strategies in patients with hepatic artery stenosis (HAS) after pediatric liver transplantation (pLT). MethodsThis is a single center observational cohort study between January 1st, 2004 and August 1st, 2023, including pLT recipients aged <18 years. The primary outcome was graft and patient survival. The secondary outcomes included incidence of biliary complications, technical success of surgery or endovascular therapy (EVT), and changes in liver function. The cut-off for early and late HAS was 14 days after pLT. ResultsAmong a total of 327 pLT patients, 4 % (n = 13) developed HAS (n = 3 early; n = 10 late). Treatments included surgical revascularization for one early HAS, conservative management with anticoagulation for one early and four late HAS, and EVT for one early and six late HAS. Over a median follow-up of 28.2 months after the diagnosis of HAS, graft survival was 100 % and 83 % in early and late HAS groups, and patient survival reached 100 % in both groups. One graft loss occurred in the conservative group. Conversely, graft survival in the EVT group was 100 %. ConclusionThe long-term outcomes of HAS after pLT are excellent. Both EVT and conservative management exhibited high graft survival rates for late HAS, with EVT achieving high technical success.

Transient Elastography for Noninvasive Evaluation of Posttransplant Liver Graft Fibrosis in Turkish Children, Ege University Children Hospital Experience.

The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage. This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy. This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8kPa ± 3.2) compared to patients with F0 fibrosis (5.2kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1kPa ± 1.5) (p = 0.041), on ANOVA. Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.