Cognitive function of children with biliary atresia after primary living donor liver transplantation.

BACKGROUND: The survival rate of children with biliary atresia (BA) after liver transplantation (LT) is significantly improved, and their quality of life has attracted much attention.This study aimed to investigate the cognition and its influencing factors in children with BA after primary living donor LT (BA-pLDLT) during infancy. METHODS: Children with BA were recruited 6 months after pLDLT at Children's Hospital of Chongqing Medical University (2018-2022). Demographic and clinical data were collected from the health information system. Cognition was assessed using the Chinese version of the Griffiths Mental Development scale (GMDS-C). Multivariate linear regression were used to analyze the influencing factors of their cognitive function. RESULTS: In total, 57 children with BA-pLDLT, aged 5.00(3.90-9.30) months at transplantation and 25.00(14.00-60.80) months at evaluation were included. The general developmental quotient (89.02 ± 12.07) and motor, language, eye-hand coordination, performance, and practical reasoning quotients of these children were significantly lower than the normative mean values of GMDS-C(P < 0.05). Of the 57 children, 16 (28.07%) had borderline developmental delay (DQ between 70 and 84), 3 (5.26%) had developmental delay (DQ < 70), and 11(19.29%) had language delay. Reoperation for biliary or vascular complications after pLDLT was a risk factor for decreased general development quotient and motor quotient and lower ZW at assessment was associated with decline motor quotient. CONCLUSION: Children with BA-pLDLT have varying degrees of developmental delays in early life. Reoperation and nutritional deficiencies had adverse effects on cognitive development.

Early life growth and developmental trajectory in children with biliary atresia undergoing primary liver transplantation.

Objective: To clarify the early growth and developmental characteristics of children with biliary atresia (BA) undergoing primary liver transplantation (pLT). Methods: A prospective cohort study, which specifically focused on BA-pLT children, was conducted after the diagnosis of BA by following the children at the time of pLT and 1, 3, 5, 7 months and 1 year after pLT for growth and developmental monitoring. The growth parameters were calculated according to the WHO standard, and the developmental status was assessed using Denver Developmental Screening Tests. Results: A total of 48 BA children who received pLT at the age of 5.00 ± 0.94 months were analyzed. The weight-for-age Z-value (ZW) and length-for-age Z-value (ZL) were higher than the head circumference-for-age Z-value (ZHC) at pLT (P = 0.002 and 0.02), but they were all lower than the WHO growth standard (Z = 0) (P < 0.001). The ZW and ZHC decreased first and then returned to the population level at 1 year after pLT, while the ZL only returned to the preoperative status and was lower than the ZW and ZHC (P < 0.001). Developmental screening showed that 35% (17/48) of the children were defined as suspicious and 15% (7/48) were abnormal at 1-4 months after pLT, the most likely time to be suspected of developmental delay. At 1 year after pLT, gross motor skill delay still existed (12/45, 27%), and language skill delay began to appear (4/45, 9%). Conclusions: BA-pLT children suffer from growth and developmental problems. Low ZHC is the main growth problem before pLT, while low ZL is the problem after pLT. Developmental delays are significant after pLT, especially in motor and language skills. The current study suggested that further studies are warranted to clarify the long-term growth and developmental outcomes of BA-pLT children, to compare them with children undergoing the Kasai procedure and to explore their influencing factors and possible mechanisms.

[Clinical Analysis of ABO-Incompatible Living-Donor Liver Transplantation in Children].

Objective: To evaluate the safety and clinical efficacy of ABO-incompatible living-donor liver transplantation (LDLT) in children. Methods: The clinical data of 62 children who underwent for the first time living donor liver transplantation in our hospital from April 2019 to July 2020 were retrospectively analyzed. According to the blood type matching of donor and recipient, the patients were divided into 3 groups, ABO-identical (ABO-Id, n=33), ABO-compatible (ABO-C, n=10) and ABO-incompatible (ABO-In, n=19), the median age of recipients in the three groups being 5 months. In the ABO-In group, 4 recipients whose condition was combined with liver failure and 2 recipients who had blood group antibody titers≥1∶32 received preoperative plasma exchange. All ABO-incompatible recipients had preoperative blood group antibody titers<1∶32. All recipients in the three groups underwent piggyback liver transplantation and received immunosuppressive and anticoagulation therapy. Postoperative follow-up was 5 to 20 months, the median being 12 months, measured until December 31, 2020 or until the date of death. Baseline clinical data, postoperative survival, and postoperative complications of recipients in the three groups were analyzed. Results: There were no significant differences in age, gender, underlying disease, operation history, Child Pugh score, donor age, graft to recipient weight ratio (GR/WR), cold ischemia time, warm ischemia time, duration of surgery, intraoperative blood loss and the use of immunosuppressants among the recipients in the three groups (all P>0.05). There was one death in the perioperative period and two deaths in the postoperative period in the ABO-Id group. There was one death in the postoperative period in the ABO-C group. There was one death in the perioperative period and one death in the postoperative period in the ABO-In group. There was no significant difference in the overall cumulative survival rate among the three groups ( P>0.05). There were no significant differences in the incidence of postoperative infection, acute rejection, biliary anastomotic stenosis and vascular complications among the three groups ( P>0.05). Conclusion: ABO-In LDLT is an effective and safe treatment option that can effectively expand the pool of live donors for liver transplantation and save the life of children with end-stage liver disease.

Learning Curve Analysis of Microvascular Hepatic Artery Anastomosis for Pediatric Living Donor Liver Transplantation: Initial Experience at A Single Institution.

Background: The incidence of hepatic artery thrombosis in pediatric living donor liver transplantation (LDLT) is significantly higher than that in adults, and is closely related to the surgeon's experience with hepatic artery anastomosis. However, there are few studies on the learning curve of hepatic artery anastomosis among surgeons. Methods: We collected data related to 75 patients who underwent pediatric LDLT and hepatic artery anastomosis independently by the same surgeon. Cumulative sum method (CUSUM) was used to analyse the duration of hepatic artery anastomosis and determine the cut-off value. Patients were divided into two phases according to CUSUM. We analysed the intraoperative and postoperative data and survival outcomes of the included patients. Results: Total anastomosis duration decreased with an increased number of completed procedures, and the average duration was 42.4 ± 2.20 min. A cut-off value and two phases were identified: 1-43 cases and 44-75 cases. Intraoperative blood loss was significantly lower in phase 2 than in phase 1. The immediate functional changes of total bilirubin (TBIL) and direct bilirubin (DBIL) were significantly also lower in phase 2 than in phase 1. Other functional outcomes, postoperative complications, and the long-term survival rate were not significantly different between the two phases. Conclusions: Technical competence in pediatric LDLT hepatic artery anastomosis may be achieved after completing 43 cases. It is a safe procedure with a surgical loupe that can be systematized and adopted by pediatric surgeons with sufficient experience via a relatively long learning curve.

Study Protocol: Design and Implementation of the Pediatric Liver Transplantation Biobank.

Background: Early treatment of neonatal biliary atresia (BA) and other end-stage liver diseases can delay or prevent the necessity of liver transplantation (LT). The establishment of a standardized clinical pediatric liver transplantation (PLT) biobank is the prerequisite for scientific research, which helps to provide a qualified sample resource platform for research. Methods: Following standardized procedures to establish biobanks, the operational processes and quality control system were formulated. Liver tissue, blood, and stool samples undergoing LT were regularly collected, managed, and stored. Systematic management was conducted in collected specimens and corresponding clinical information. Results: Since implementation in August 2018, we have enrolled 49 unique subjects (0-18 years of age); the biobank contains nearly 3000 biospecimen aliquots. The most common LT diagnosis is BA (61.23%). Conclusion: The establishment of this biobank is a valuable resource that incorporates detailed clinical and biological information. It will help accelerate the pace of PLT discovery research. ClinicalTrials.gov ID: NCT04477967.

Application of 3-Dimensional Printing in Pediatric Living Donor Liver Transplantation: A Single-Center Experience.

Three-dimensional (3D) printing has been used to support organ transplantations. However, whether it helps remains unclear. This study aimed to present and assess the application of 3D-printed liver models in pediatric living donor liver transplantation (LDLT). The 3D images were printed to touchable liver models with transparent liver parenchyma, specifically colored hepatic vessels, and biliary structures. A total of 30 consecutive recipients were enrolled in the study: 10 were operated on with the support of 3D printing (3D-printing group) and 20 (control group) were operated on without it. Detailed photographs and data of the cases in the 3D-printing group were presented. One patient underwent auxiliary partial orthotopic liver transplantation using the left lobe graft, in which the abdominal cavity model was also printed to test whether the planned graft fit the recipient's abdominal cavity. The 3D-printed models facilitated surgical planning and procedures, particularly in the management of hepatic veins and in the prevention of large-for-size syndrome. The operative time of donors in the 3D-printing group was significantly shorter compared with the control group (2.3 ± 0.4 versus 3.0 ± 0.4 hours; P < 0.001). Inpatient costs for donors in the 3D-printing group were 17.1% lower than those in the control group (34.6 ± 6.6 versus 41.7 ± 10.4 thousand ¥; P = 0.03). In conclusion, in small infants and complicated pediatric LDLT patients, 3D-printed models can help minimize the risk of large-for-size syndrome and graft reduction. The 3D-printed models may be conducive to liver graft procurement and intraoperative assistance in pediatric LDLT.

Crystalloid fluid administration was associated with outcomes in pediatric patients with severe sepsis or septic shock.

Intravenous fluid prescription plays an important role in sepsis management, which may be associated with patient prognosis. The objective of the present study was to determine if the administration of crystalloid fluids is associated with clinical outcome for patients with severe sepsis and septic shock.The medical records of 79 patients with severe sepsis or septic shock at an academic tertiary care hospital between 2011 and 2016 were reviewed retrospectively. The patients were dichotomized based on the median 3-day amount of corrected crystalloid fluids as low (<193 mL/kg) versus high (>193 mL/kg). The primary outcome measure was mortality. Secondary outcome measures included length of stay in the pediatric intensive care unit (PICU), usage of mechanical ventilation, etc.The most common bacterial pathogens were Escherichia coli and Klebsiella spp. with a strikingly high number of multidrug-resistant infections (10.1%). The most common site of infection was of abdominal origin. Patients who received larger amounts of crystalloids were more likely to have lower weight and underlying comorbidities (high PRISM score). Although fluid intake was different in the 2 groups, output volumes were almost the same; therefore, a positive fluid balance was present in the high crystalloid patients. The incidence of mortality increased as the accumulated 3-day amount of crystalloid fluids administered increased. The total length of stay in the PICU was longer for patients who received high volume crystalloid fluid (15.8 ±â€Š7.8 days) than for patients who received the lower volume (9.7 ±â€Š5.3 days, P = .026).A higher amount of 3-day crystalloid administration was unfavorable for postoperative outcomes in children with sepsis and septic shock; these patients experienced higher PICU mortality, longer PICU stays, and more ventilator days. More study on the benefits and harms of fluid in children are needed to improve patient safety and the quality of care that would facilitate better outcomes.

Usage of 64-detector-row spiral computed tomography volumetry in preoperative volume prediction in living donor liver transplantation in children.

PURPOSE: To investigate the correlation between the graft volume calculated by 64-detector-row spiral computed tomography (CT) and the graft weight measured during the living donor liver transplantation (LDLT) operation, and try to get an equation to help determine the possible weight of graft before operation. METHODS: 23 donors with left lateral lobe LDLT were enrolled to undergo 64-detector-row spiral CT and the imaging data at the hepatic venous phase was used for whole and partial liver volumetric measurement on a dedicated image postprocessing workstation. The resected part of donor liver was weighed during the operation. Statistical analysis with SPSS15.0 was used to analyze the correlation between the estimated liver volume by CT and the actual graft weight. RESULTS: The graft volume calculated preoperatively by CT (293.35 ± 53.43 ml) was significantly larger than measured graft weight during the operation (252.82 ± 50.96 g) (P < 0.05). All corresponding pre- and intraoperative data correlated significantly (R = 0.885) (P < 0.001). Intraoperatively expected weight (W (intraop)) in grams and volume calculated preoperatively by CT (V (preop)) in milliliters can be calculated with the equation W (intraop) (g) = 0.844 × V (preop) (ml) + 5.271. CONCLUSION: Liver volume calculated by 64-detector-row spiral CT preoperatively can predict the actual graft weight, which is very useful in donor selection in LDLT.

[Clinical study of 28 patients with adult-to-infant living donor liver transplantation].

OBJECTIVE: To summarize our experience in adult-to-infant living donor liver transplantation (A-ILDLT) and to analyze the efficacy and complications of A-ILDLT. METHODS: The clinical data, surgical strategies and complications of 28 adult donors and infantile recipients who underwent A-ILDLT from April 2006 to December 2009 were retrospectively analyzed. These 28 patients (14 boys and 14 girls) aged from 80 days to 11.5 months with body weights of 3.08 to 10.3 kg at the time of operation . They suffered from biliary atresia with decompensated cirrhosis. The living donors were 15 mothers, 9 fathers, 3 grandma and 1 elder brother with ABO compatible with the infantile recipients. 27 Donor organs were the left lateral lobe grafts (segment II, III) and 1 graft was segment II. All patients were followed up for 5 to 24 months. RESULTS: These grafts were orthotopically transplanted into the infantile recipients. The average length of stay was 9.3 days for the donor group without any complications. Postoperative immunosuppression included prednisone, Cyclosporin and mycophenolate mofetil (MMF). A total of 24 postoperative complications occurred in 20 recipients, including 5 vascular complications, 4 bleeding, 7 pneumonia, 2 bowel obstruction, 4 intestinal perforation and 3 rejection. Three recipients died of hepatic arterial thrombosis (HAT). The perioperative mortality rate of recipients was 10.7% (3/28) and the survival rate was 89.3% in peroperative period. One died of stricture of hepatic vein and 1 of accidental asphyxia during follow-up term. At present, 23 cases are still alive. CONCLUSION: A-ILDLT has become an effective method to infants with end-stage liver disease. The postoperative vascular complication is the predominant cause of death.

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation: a meta-analysis.

AIM: To assess the effect of human leukocyte antigen (HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies. METHODS: Articles in PubMed/MEDLINE, EMBASE and the Cochrane database from January 1970 to June 2009, including non-English literature identified in these databases, were searched. Only studies comparing HLA or sub-phenotype matching with mismatching were extracted. The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed. A meta-analysis was performed when at least 3 studies provided data. RESULTS: Sixteen studies met the inclusion criteria. A lower number of HLA mismatches (0-2 vs 3-6) did reduce the incidence of acute rejection (relative risk: 0.77, P = 0.03). The degree of HLA mismatching (0-2 vs 3-6) had no significant effect on 1-year [hazard ratio (HR): 1.04, P = 0.68] and 5-year (HR: 1.09, P = 0.38) graft survival. In sub-phenotype analysis, the degree of HLA-A, B and DR mismatching (0 vs 1-2) had no significant effect on 1-year and 5-year graft survival, either. The HRs and P-values were 0.95, 0.71 (HLA-A, 1-year); 1.06, 0.60 (HLA-A, 5-year); 0.77, 0.16 (HLA-B, 1-year); 1.07, 0.56 (HLA-DR, 1-year); 1.18, 0.23 (HLA-DR, 5-year), respectively. CONCLUSION: The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes. To obtain a short recovery time and minimize rejection post transplantation, HLA matching studies should be considered before the operation.