Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease:A retrospective observational study

BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pediatric liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two groups.AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019.ALF and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient survival.RESULTS Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for ALF.The ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD group.Post-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF group.Once the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.

Effect of remote ischemic preconditioning among donors and recipients following pediatric liver transplantation:A randomized clinical trial

BACKGROUND Studies suggested that remote ischemic preconditioning(RIPC)may effectively lessen the harmful effects of ischemia reperfusion injury during organ transplantation surgery.AIM To investigate the protective effects of RIPC on living liver donors and recipients following pediatric liver transplantation.METHODS From January 2016 to January 2019 at Renji Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,208 donors were recruited and randomly assigned to four groups:S-RIPC group(no intervention;n=55),D-RIPC group(donors received RIPC;n=51),R-RIPC group(recipients received RIPC,n=51)and DR-RIPC group(both donors and recipients received RIPC;n=51).We primarily evaluated postoperative liver function among donors and recipients and incidences of early allograft dysfunction,primary nonfunction and postoperative complications among recipients.RESULTS RIPC did not significantly improve alanine transaminase and aspartate aminotransferase levels among donors and recipients or decrease the incidences of early allograft dysfunction,primary nonfunction,and postoperative complications among recipients.Limited protective effects were observed,including a lower creatinine level in the D-RIPC group than in the S-RIPC group on postoperative day 0(P<0.05).However,no significant improvements were found in donors who received RIPC.Furthermore,RIPC had no effects on the overall survival of recipients.CONCLUSION The protective effects of RIPC were limited for recipients who received living liver transplantation,and no significant improvement of the prognosis was observed in recipients.

Balloon dilatation for treatment of hepatic venous outflow obstruction following pediatric liver transplantation

AIM To assess the efficacy and safety of balloon dilatation for the treatment of hepatic venous outflow obstruction(HVOO) following pediatric liver transplantation.METHODS A total of 246 pediatric patients underwent liver transplantation at our hospital between June 2013 and September 2016. Among these patients, five were ultimately diagnosed with HVOO. Seven procedures(two patients underwent two balloon dilatation procedures) were included in this analysis. The demographic data,types of donor and liver transplant, interventional examination and therapeutic outcomes of these five children were analyzed. The median interval time between pediatric liver transplantation and balloon dilatation procedures was 9.8 mo(range: 1-32).RESULTS Five children with HVOO were successfully treated by balloon angioplasty without stent placement, with seven procedures performed for six stenotic lesions. All children underwent successful percutaneous intervention. Among these five patients, four were treated by single balloon angioplasty, and these patients did not develop recurrent stenosis. In seven episodes of balloon angioplasty across the stenosis, the pressure gradient was 12.0 ± 8.8 mm Hg before balloon dilatation and 1.1 ± 1.5 mm Hg after the procedures, which revealed a statistically significant reduction(P < 0.05). The overall technical success rate among these seven procedures was 100%(7/7), and clinical success was achieved in all five patients(100%). The patients were followed for 4-33 mo(median: 15 mo). No significant procedural complications or procedurerelated deaths occurred.CONCLUSION Balloon dilatation is an effective and safe therapeutic option for HVOO in children undergoing pediatric liver transplantation. Venous angioplasty is also recommended in cases with recurrent HVOO.

Hepatic artery reconstruction in pediatric liver transplantation:Experience from a single group

Background:The reconstruction of hepatic artery is a challenging part of the pediatric liver transplantation procedure.Hepatic artery thrombosis(HAT)and stenosis are complications which may result in ischemic biliary injury,causing early graft lost and even death.Methods:Two hundred and fifty-nine patients underwent liver transplantation in 2017 in a single liver transplantation group.Among them,225 patients were living donor liver transplantation(LDLT)and 34 deceased donor liver transplantation(DDLT).Results:In LDLT all reconstructions of hepatic artery were microsurgical,while in DDLT either microsurgical reconstruction or traditional continuous suture technique was done depending on different conditions.There were five(1.9%)HATs:four(4/34,11.8%)in DDLT(all whole liver grafts)and one(1/225,0.4%)in LDLT(P=0.001).Four HATs were managed conservatively using anticoagulation,and 1 accepted salvage surgery with re-anastomosis.Until now,3 HAT patients remain in good condition,whereas two developed biliary complications.One of them needed to be re-transplanted,and the other patient died due to biliary complications.Conclusions:Microsurgical technique significantly improves the reconstruction of hepatic artery in pediatric liver transplantation.The risk for arterial complications is higher in DDLT.Conservative therapy can achieve good outcome in selected HAT cases.

Differences in parents of pediatric liver transplantation and chronic liver disease patients

BACKGROUND With advancements in the treatment of chronic liver disease(CLD),including liver transplantation(LT),quality of life and satisfaction after LT have become an important issue for pediatric patients and their parents.More evidence-based information is needed to describe and assess the impact of pediatric CLD on parents and the satisfaction of parents with treatment to better understand their needs.AIM To assess the satisfaction of parents of pediatric LT patients and that of parents of pediatric CLD patients METHODS During this survey,data were collected from parents of pediatric patients who underwent LT between January 2010 and April 2017(LT group;n=91)and parents of pediatric patients with chronic liver disease(CLD group;n=94).Group comparisons were made based on the pediatric health-related quality of life(PedsQL)health care parent satisfaction scale,impact on family scale(IFS)and demographic characteristics.The PedsQL was administered to parents during a phone interview and the results were used to assess the health carerelated satisfaction of parents.The IFS was used to assess the impact of the child’s CLD status on the family.Demographic variables such as education level(elementary vs middle vs high vs university),monthly income(low vs middle vs high),and place of residence(village vs town vs city)were compared between CLD and LT parent groups.Finally,PedsQL and IFS results were also analyzed according to demographic variables.RESULTS A total of 185 parents aged 19 to 65 years were included.There were statistically significant differences between the LT and CLD groups in terms of career(P<0.001),monthly income(P=0.016),and education level(P=0.041).According to the PedsQL results,family inclusion,communication,technical skills,emotional needs,and overall satisfaction were significantly different between the groups;the LT group had consistently higher scores(P<0.001).Additionally,scores for the IFS parameters of financial impact,familial-social impact,personal strain,and total impact were consistently higher for the LT group(P<0.001).There were statistically significant relationships between education level,monthly income,and place of residence according to the IFS results but not the PedsQL results.There were inverse relationships between the difficulties that parents experience because of their child’s health and education levels,monthly income,and place of residence.However,no relationship was found between education level,monthly income,or place of residence and satisfaction with health care services provided in the hospital according to the PedsQL results.CONCLUSION Parents of children who underwent LT were very satisfied with the health care services provided to their children.However,they had more difficulties than parents of children with CLD.

Perioperative anesthesia management in pediatric liver transplant recipient with atrial septal defect:A case report

BACKGROUND Preoperative conditions in pediatric liver transplant recipients are understandably complex.Compared with adults,children have lesser compensatory abilities and demand greater precision during procedural executions.In the setting of endstage liver disease,the heightened perioperative risk of coexistent cardiovascular pathology may impact graft survival as well.Requirements for anesthesia and perioperative management are thus more rigorous,calling for individualized treatments that reflect specific cardiovascular constraints and proposed surgical plans.CASE SUMMARY Reports of perioperative anesthesia management and liver transplant prognostication in pediatric patients with concurrent atrial septal defects are scarce.Herein,we detail the course of liver transplantation in a child with dual afflictions,focusing on perioperative anesthesia management and the important contributions of the anesthesiologist(pre-and perioperatively) to a positive therapeutic outcome,despite the clinical hurdles imposed.CONCLUSION Children with atrial septal defects bear substantially more than customary perioperative risk during orthotopic liver transplants,given their compromised cardiopulmonary reserves and functional states.Comprehensive preoperative cardiovascular assessments,including use of agitated-saline contrast echocardiography(to characterize intracardiac shunting) and multidisciplinary deliberation,may offer insights into structural cardiac pathophysiologic effects and transplantrelated hemodynamic changes that impact new grafts.At the same time,active and effective monitoring and other measures should be taken to maintain hemodynamic stability in the perioperative period,avoid entry of bubbles into the circulation,and ease congestion in newly grafted livers.Such efforts are crucial for transplantation success and graft survival.

Development and validation of a nomogram to predict allograft survival after pediatric liver transplantation

Background Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in children.However,no accurate prediction model to determine the survival probability of grafts prior to surgery exists.This study aimed to develop an effective prognostic model for allograft survival after pediatric liver transplantation.Methods This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1,2006,and January 1,2020.A nomogram was developed using Cox regression and validated based on bootstrap sampling.Predictive and discriminatory accuracies were determined using the concordance index and visualized using calibration curves;net benefits were calculated for model comparison.An online Shiny application was developed for easy access to the model.Results Multivariable analysis demonstrated that preoperative diagnosis,recipient age,body weight,graft type,preoperative total bilirubin,interleukin-1β,portal venous blood flow direction,spleen thickness,and the presence of heart disease and cholangitis were independent factors for survival,all of which were selected in the nomogram.Calibration of the nomogram indicated that the 1-,3-,and 5-year predicted survival rates agreed with the actual survival rate.The concordance indices for graft survival at 1,3,and 5 years were 0.776,0.757,and 0.753,respectively,which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring systems.The allograft dysfunction risk of a recipient could be easily predicted using the following URL:https://aspelt.shinyapps.io/ASPELT/l Conclusion The allograft survival after pediatric liver transplantation(ASPELT)score model can effectively predict the graft survival rate after liver transplantation in children,providing a simple and convenient evaluation method for clinicians and patients.

Qualifying the suitability of living donor livers for pediatric liver transplantation:are we doing the right thing?

Over the last decades,liver transplantation has become the standard care for many forms of end-stage liver disease,both in adults and in children.The prognosis after pediatric liver transplantation(pLT)has steadily increased up to a patient survival at 5 years of 85%and an estimated graft half life of 31 years(1,2).In the early days of pLT,the transplanted organ originated from deceased donors.Since 1990,adult-to-child living donor liver transplantation(LDLT)programs have developed,which rapidly gained popularity,particularly in Europe and Asia(2,3).A major stimulus for LDLT has been the limited availability of deceased donors.The indications for liver transplantation have expanded,particularly for adult patients,at a higher rate than the availability of donor organs.Moreover,the quality of donor organs has steadily declined,resulting in a decreased utilization of livers from deceased donors for transplantation(4).The limited availability of qualified deceased donor livers has further stimulated LDLT:in Europe,for example,the percentage of living donor organs used for pLT increased from 7%before 2000 to 40%since 2010(1).

Pediatric liver transplantation in 31 consecutive children

Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children （≤18 years old） underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old （ranged from 5 months to 18 years） with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson＇s disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard （without venovenous bypass）, 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug （FK506, steroid, and mycophenolate mofetil） immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus （HBV） or hepatitis C virus （HCV） infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively. Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients＇ age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher surgical skills. The early postoperative management is the key to success. Postoperative bile leak was common, but most patients underwent liver transplantation had a better prognosis.

Comment on pediatric living donor liver transplantation decade progress in Shanghai: Characteristics and risks factors of mortality

Since the first successful liver transplantation was performed five decades ago,pediatric liver transplantation has become the gold standard treatment choice for pediatric liver disease,including metabolic diseases,liver tumors,and some acute liver failure.With improvements in immunosuppression,surgical techniques,and postoperative medical care,long-term outcomes of patients after liver transplantation have markedly improved,especially in pediatric patients.

Laparoscopic left lateral sectionectomy in pediatric living donor liver transplantation by single-port approach:A case report

BACKGROUND Single-port laparoscopy has been used in a variety of abdominal operations.We report the first case of single-port laparoscopic left lateral sectionectomy in pediatric laparoscopic living donor liver transplantation.CASE SUMMARY A 28-year-old man volunteered for living liver donation to his daughter who was diagnosed with liver cirrhosis and portal hypertension after the Kasai procedure for biliary atresia.His body mass index was 20.5 kg/m2.Liver dynamic computed tomography showed:(1)Left lateral graft volume of 232.76 cm3 with a graft-torecipient weight ratio of 2.59%;and(2)Right hepatic artery derived from the superior mesenteric artery.A single-port access system was placed through a transumbilical incision,including four trocars:two 12-mm ports for a camera and endoscopic stapler and two 5-mm working ports.Liver parenchyma was dissected by a Harmonic and Cavitron Ultrasonic Surgical Aspirator,while bipolar was used for coagulation.The bile duct was transected above the bifurcation by indocyanine green fluorescence cholangiography.The specimen was retrieved from the umbilical incision.The total operation time was 4 h without blood transfusion.The final graft weight was 233.6 g with graft-torecipient weight ratio of 2.60%.The donor was discharged uneventfully on postoperative day 4.CONCLUSION Single-port laparoscopic left lateral sectionectomy is feasible in pediatric laparoscopic living donor liver transplantation in an experienced transplant center.

Impact of living donor liver with steatosis and idiopathic portal inflammation on clinical outcomes in pediatric liver transplantation:Beijing experience

Background:To evaluate the impact of steatosis and/or idiopathic portal inflammation(IPI)in living donor livers on recipients’clinical outcomes.Methods:We assessed 305 qualified donor liver samples from June 2013 to December 2018.Donors and recipients’clinical characteristics,including follow-up data were retrieved.The graft and overall survival with/without steatosis or portal inflammation were compared by Kaplan-Meier analysis.Results:For living donors,the medium age of was 31.2(28,35.8)years old;liver histopathology showed macrovesicular steatosis:0-5%264/305(86.6%)and 5-30%41/305(13.4%),IPI:no 220/305(72.1%)and mild 85/305(27.9%).For recipients,the medium age was 1.0(0.6,1.5)years old;the median pediatric-end-stage-liver-disease score was 16(5.0,26.0)and medium follow-up time was 32.8(24.8,52.0)months.Biliary atresia(69.5%)was the main indication for liver transplantation(LT).Conclusions:The presence of steatosis and portal inflammation of the donor liver did not impact the clinical outcomes including transaminase or bilirubin normalization,short-/long-term complications and recipients’survival.However,recipients with high pediatric-end-stage-liver-disease score(>16)receiving donor liver with portal inflammation,but not steatosis,had trend negative effect on recipients’survival.In conclusion,donor livers with mild steatosis and portal inflammation were qualified for pediatric living donor LT.However,donor liver with mild portal inflammation would better not be allocated to recipients with high pediatric-end-stage-liver-disease score.This study provided new evidence in pediatric living donor liver allocation.

Pediatric living donor liver transplantation using liver allograft after ex vivo backtable resection of hemangioma: A case report

BACKGROUND Use of liver allograft with hepatic hemangioma after in vivo resection of hemangioma in living donor liver transplantation(LDLT)has been previously reported.However,there are few reports describing ex vivo backtable resection of hemangioma from liver allografts in LDLT.CASE SUMMARY A 55-year-old male was evaluated as a donor for an 8-month-year old patient with acute hepatic failure due to biliary atresia.Pre-operative contrast enhanced computed tomography revealed a 9 cm hemangioma in segment 4 with vascular variations in the donor.During LDLT,an intra-operative intrahepatic cholangiography was performed to ensure no variation in the anatomy of the intrahepatic bile duct.After intra-operative pathological diagnosis,ex vivo backtable resection of the hemangioma was performed and the liver allograft was transplanted into the recipient.The donor’s and recipient’s post-operative course were uneventful.At the 2-year follow-up,the liver allograft showed good regeneration without any recurrence of hemangioma.CONCLUSION Liver allografts with hemangiomas are an acceptable alternative strategy for LDLT.Ex vivo backtable resection of hemangioma from the donor liver during pediatric LDLT is safe and feasible,and can effectively reduce the operative time and intra-operative bleeding for the donor.

Association of different central venous pressure levels with outcome of living-donor liver transplantation in children under 12 years

Background 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.Methods 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.Results 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).Conclusion 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.

Advanced therapies for congenital biliary tract malformation:From bench to bedside

Congenital biliary tract malformations are a series of rare but extremely serious diseases that mainly include biliary atresia and biliary hypoplasia(referred to as Alagille syndrome).The rapid progression of biliary atresia and Alagille syndrome results in jaundice,cholestatic liver disease,cirrhosis,and even liver failure.In most cases,supportive or clinically specific therapies cannot achieve satisfactory outcomes.Therefore,liver transplantation(especially living donor liver transplantation)may be required.As many studies have elucidated the role of genetic factors and the molecular mechanism of congenital biliary tract malformations,experimental therapies such as organoid transplantation,cell therapy,and immunotherapy have been proved to be feasible.These advanced methods have shown outstanding advantages,particularly in patients with end-stage biliary tract malformations,surgery failure,and other problems that cannot be solved by conventional therapies.This review article discusses the potential pathogenesis of and promising therapeutic strategies for biliary tract malformations.