Pediatric Living Donor Liver Transplantation Research Articles

ABO incompatible living donor liver transplantation in children: A single centre experience from India

BackgroundIn recent years, pediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report pediatric ABOi LT experience including short- and long-term outcomes. MethodsIt is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n=20) and non-ABOi (n=220) pediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. ResultsOut of 239 pediatric LDLT from 2017-2022, 19 children (11 females) underwent 20 ABOi LT (including one retransplant with ABOi domino allograft) at a median age of 12(12,51) months with majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day -14 to day -1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture proven sepsis, biliary and vascular complications were seen in 10%, 20%, 20%, and 15% respectively. None of the ABOi LT recipients developed antibody mediated rejection. ABOi LT recipients as compared to non ABOi LT had higher incidence of bile leak and prolonged hospital stay with rest of the complications including biliary strictures and long-term outcome being comparable. At a median follow up of 21(14,33) months, 4 children expired (21%). ConclusionABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when compatible liver is unavailable.

Prediction of early recovery of graft function after living donor liver transplantation in children

For end-stage liver disease in children, living donor liver transplantation (LDLT) is often the important standard curative treatment. However, there is a lack of research on early recovery of graft function after pediatric LDLT. This is a single-center, ambispective cohort study. We collected the demographic and clinicopathological data of donors and recipients, and determined the risk factors of postoperative delayed recovery of hepatic function (DRHF) by univariate and multivariate Logistic analyses. 181 cases were included in the retrospective cohort and 50 cases in the prospective cohort. The incidence of DRHF after LDLT in children was 29.4%, and DRHF could well evaluate the early recovery of graft function after LDLT. Through Logistic analyses and AIC score, preoperative liver function of donors, ischemia duration level of the liver graft, Ln (Cr of recipients before operation) and Ln (TB of recipients on the 3rd day after operation) were predictive indicators for DRHF after LDLT in children. Using the above factors, we constructed a predictive model to evaluate the incidence of postoperative DRHF. Self-verification and prospective internal verification showed that this prediction model had good accuracy and clinical applicability. In conclusion, we pointed many risk factors for early delayed recovery of graft function after LDLT in children, and developed a visual and personalized predictive model for them, offering valuable insights for clinical management.

Outcomes of 6000 living donor liver transplantation procedures: a pioneering experience at ASAN Medical Center.

Living donor liver transplantation (LDLT) has emerged as a favorable alternative to deceased donor liver transplantation, significantly reducing waitlist mortality, particularly in Asian countries with very low deceased organ donation rates. Asan Medical Center (AMC) in South Korea has pioneered innovative LDLT surgical techniques and become established as an extremely high-volume center for LDLT. This retrospective study analyzed 6000 consecutive LDLT procedures, including 510 dual-graft procedures, performed at AMC between December 1994 and January 2021. Of these, 312 LDLT procedures were performed in children aged < 18years. In adult recipients, liver cirrhosis (LC) related to viral hepatitis was the most common indication, occurring in 69.8% of cases. Biliary atresia (46.8%) was the most common indication for pediatric LDLT. This study demonstrated outstanding long-term outcomes, with patient survival rates at 1, 5, 10, and 20years of 92.7%, 85.9%, 82.1%, and 70.9%, respectively, in LDLT group for adults aged 50 and under at the time of LDLT, and 92.9%, 89.0%, 88.1%, and 81.9%, respectively, in the pediatric group. The in-hospital mortality rate of adult recipients was 3.8% (n = 214/5688). This study demonstrates the importance of refined surgical techniques, selection of grafts tailored to the recipient, and comprehensive multidisciplinary perioperative patient care in expanding the scope of LDLT and improving recipient outcomes.

Ischemia and reperfusion-injured liver-derived exosomes elicit acute lung injury through miR-122-5p regulated alveolar macrophage polarization

Acute lung injury (ALI) is a common postoperative complication, particularly in pediatric patients after liver transplantation. Hepatic ischemia–reperfusion (HIR) increases the release of exosomes (IR-Exos) in peripheral circulation. However, the role of IR-Exos in the pathogenesis of ALI induced by HIR remains unclear. Here, we explored the role of exosomes derived from the HIR-injured liver in ALI development. Intravenous injection of IR-Exos caused lung inflammation in naive rats, whereas pretreatment with an inhibitor of exosomal secretion (GW4869) attenuated HIR-related lung injury. In vivo and in vitro results show that IR-Exos promoted proinflammatory responses and M1 macrophage polarization. Furthermore, miRNA profiling of serum identified miR-122-5p as the exosomal miRNA with the highest increase in young rats with HIR compared with controls. Additionally, IR-Exos transferred miR-122-5p to macrophages and promoted proinflammatory responses and M1 phenotype polarization by targeting suppressor of cytokine signaling protein 1(SOCS-1)/nuclear factor (NF)-κB. Importantly, the pathological role of exosomal miR-122-5p in initiating lung inflammation was reversed by inhibition of miR-122-5p. Clinically, high levels of miR-122-5p were found in serum and correlated to the severity of lung injury in pediatric living-donor liver transplant recipients with ALI. Taken together, our findings reveal that IR-Exos transfer liver-specific miR-122-5p to alveolar macrophages and elicit ALI by inducing M1 macrophage polarization via the SOCS-1/NF-κB signaling pathway.

Epidemiology and Risk Factors of Early Bacterial Infections After Pediatric Living Donor Liver Transplantation

Advancements in surgical techniques, immunosuppression regimens, and peri-operative and postoperative care have resulted in marked improvement in outcomes after pediatric living donor liver transplantation (PLDLT). Despite these developments, infectious complications remain a major cause of morbidity and mortality. This is a retrospective cohort analysis of pediatric recipients from January 2004 to December 2018. Patients were classified into infected and non-infected groups based on the occurrence of bacterial infection during the first 3 months after transplant. Perioperative risk factors for early post-transplant bacterial infections and postoperative outcomes were investigated. Seventy-two out of 221 children developed early bacterial infection (32.6%). The first episodes of bacterial infection most frequently occurred in the second week after LDLT (37.5%). In multivariate analysis, active infection before transplant and complications with Clavien-Dindo grading >3 were the only independent risk factors. Early bacterial infections were independently associated with longer intensive care unit stays, longer hospital stays, and a higher incidence of readmission for bacterial infection during the first year after transplant. Additionally, the overall patient survival rate was significantly higher in the non-infected group (P = .001). Risk factors for infection, such as age, weight, disease severity, ABO-incompatible, and other operative factors, were not identified as independent risk factors. We have demonstrated that there are similarities and disparities in the epidemiology and risk factors for early bacterial infection after transplant between centers. Identification and better characterization of these predisposing factors are essential in the modification of current preventive strategies and treatment protocols to improve outcomes for this highly vulnerable group.

Clinical Implications of Serum Mac-2 Binding Protein in Patients After Living Donor Liver Transplantation for Biliary Atresia

Background: Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histological findings in patients after LDLT for biliary atresia (BA) Methods: Patients aged <19 years who underwent LDLT for BA at our institution and followed for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathological findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathological fibrosis scores and PV stenosis findings Results: The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 COI(Cut Off Index) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (p=0.016) and F1 (p=0.012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n=5) and 0.72 COI in patients without PV complications (n=51) (p=0.0001) Conclusions: M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation

Paying attention to the value of thrombelastography and the impact of postreperfusion syndrome on outcomes of liver transplantation.

Only limited information is available about the connection between massive blood transfusion and postoperative survival rates in pediatric liver transplantation. The aim of Gordon's study was to examine the potential impact of perioperative transfusion on postoperative complications and death in young children receiving pediatric living-donor liver transplantation (PLDLT). The authors concluded that transfusion of a red blood cell volume higher than 27.5 mL/kg during the perioperative period is associated with a significant increase in short- and long-term postoperative morbidity and mortality after PLDLT. However, viscoelastic coagulation monitoring was not utilized in the study; instead, only conventional coagulation monitoring was conducted. Overall, the choice of blood coagulation monitoring method during blood transfusion can have a significant impact on patient prognosis. Several studies have shown that the viscoelastic coagulation testing such as thrombelastography (TEG) is highly sensitive and accurate for diagnosing coagulation dysfunction. Indeed, a TEG-guided blood transfusion strategy can improve prognosis. Moreover, postreperfusion syndrome is one of the most common complications of liver transplantation and an important factor affecting the prognosis of patients and should also be included in regression analysis.

Peri-operative extracorporeal membrane oxygenation in adult and pediatric living donor liver transplantation: a single-center experience.

Extracorporeal membrane oxygenation (ECMO) is a potential rescue therapy for patients with acute cardiopulmonary dysfunction refractory to conventional treatment. In this study, we described the clinical profiles and outcomes of adult and pediatric living donor liver transplantation (LDLT) patients who received ECMO support during the peri-operative period. From June 1994 to December 2020, eleven out of the 1,812 LDLTs performed at Kaohsiung Chang Gung Memorial Hospital required ECMO support: six for respiratory failure, three for cardiogenic shock, and two for refractory septic shock. Comparison between the survivor and non-survivor groups was made. The survival rate for liver transplantation (LT) patients on ECMO support is 36.4%-40% in adults and 33.3% in pediatrics, while the survival rate per indication is as follows: acute respiratory distress syndrome (ARDS) (50%), cardiogenic shock (33.3%), and sepsis (0%). Shorter durations of LT-to-ECMO and pre-ECMO mechanical ventilation were observed in the survivor group. On the other hand, we observed persistently elevated total bilirubin levels in non-survivors, while none of the survivors had aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels >1,000 U/L. A higher proportion of non-survivors were on concurrent continuous renal replacement therapy (CRRT). Our experience has proven ECMO's utility during the peri-operative period for both adult and pediatric LDLT patients, more specifically for indications other than septic shock. Further studies are needed to better understand the factors leading to poor outcomes in order to identify patients who will more likely benefit from ECMO.

Prevention and management of portal vein complications after pediatric living donor liver transplantation

Prevention and management of portal vein complications after pediatric living donor liver transplantation

Pediatric living donor liver transplantation from adult allograft liver after resection of focal nodular hyperplasia: a case series study

Pediatric living donor liver transplantation from adult allograft liver after resection of focal nodular hyperplasia: a case series study

Outcome of pediatric living donor liver transplant: Experience from Pakistan; a resource limited setting.

Liver transplantation (LT) has emerged as a lifesaving modality for many liver diseases in children. Pediatric LT is an established treatment in the Western world but is relatively a new procedure in resource-limited countries like Pakistan. The study aims to highlight the outcomes and survival of pediatric recipients from the first pediatric liver transplant center in Pakistan. A retrospective analysis of pediatric LT was done from 2012 to 2019. The study was conducted in the Hepatobiliary and liver transplant department of Shifa International Hospital (SIH), Islamabad. A detailed analysis for indications for pediatric LT, survival, and complications was done. Forty-five patients under 18 years of age underwent Living donor liver transplant (LDLT) in SIH. Median age was 9 years and M:F of 2:1. Cryptogenic liver disease followed by Wilson disease were the two most common indications of LT. The majority of patients had chronic liver disease 34 (75%) while 11 (24%) had acute liver failure. The right lobe graft was the most common type of graft 19 (42.2%). Thirty days, 1-year, 3-year, and 5-year survival was 77.8%, 75.6%, 73.3%, and 60.6% respectively. Mortality was highest in patients with biliary atresia 4 (33%). Causes of death included pulmonary embolism, sepsis, surgical complications, and acute kidney injury. Mean survival was 88.850 months (±7.899) (CI 73.369-104.331). Pediatric LDLT has offered disease-free survival for patients. Survival can improve further with nutritional rehabilitation and anticipation and management of post-operative complications.

The advantages of duct-to-duct biliary reconstruction in pediatric living donor liver transplantation.

Whether Roux-en-Y hepatic jejunectomy (HJ) or duct-to-duct biliary reconstruction (DD) is more useful in pediatric living donor liver transplantation has not yet been fully investigated. Therefore, to assess the feasibility and safety of DD, we compared the surgical outcomes of DD to HJ. We divided 45 patients, excluding those with biliary atresia, into the DD group (n = 20) and the HJ group (n = 25), according to the type of biliary reconstruction they received. The 5-year survival rates (DD vs. HJ = 79.7% vs. 83.6%, p = 0.70) and the incidence of biliary complications, including bile leakage and stricture (DD vs. HJ = 1 [5.0%] vs. 1 [4.0%], p = 0.87) were not significantly different between the groups. However, intestinal complications, including bowel perforation or ileus, were significantly common in the HJ group (9/25 [36.0%]) than in the DD group (1/20 [5.0%]; p = 0.01). The three patients in the HJ group with intestinal perforation all suffered perforation at the anastomosed site in the Roux-en-Y procedure. The subgroup analysis showed the non-inferiority of DD to HJ for biliary or intestinal complications in patients weighting < 10kg. With a proper selection of cases, DD should be a safe method for biliary reconstruction in pediatric recipients with little risk of biliary complications equivalent to HJ and a reduced risk of intestinal complications.

Short limb in biliary tract reconstruction: A retrospective study of living donor liver transplantation in children with biliary atresia.

Roux-en-Y cholangiojejunostomy is a standard procedure for biliary reconstruction in pediatric living donor liver transplantation (LDLT). However, there is uncertainty on whether the adult standard of Roux branch limb is suitable for pediatric LDLT and its impact on postoperative biliary complications (BC). This study aimed to explore the effect of the short Roux limb and standard limb on pediatric LDLT biliary reconstruction. According to the length of the Roux limb, 168 LDLT children were divided into the routine limb group (n = 108) and the short limb group (n = 60). The incidences of postoperative biliary tract complications between the 2 groups were compared retrospectively. The mean Roux limb length in the short limb group was significantly shorter than that in the routine limb group group (P < .01). There were significant differences in age, height, and weight between the 2 groups (P < .01). However, there were no significant differences in graft-to-recipient weight ratio, intraoperative blood loss, cold ischemia time, and operation time between the 2 groups (P > .01). Moreover, postoperative BC, including refluxing cholangitis, were similar between the 2 groups (P = .876). Furthermore, the history of Kasai surgery, the history of postoperative RC of Kasai, and whether or not the Roux limb was reconstructed had no significant effect on the occurrence of postoperative RC. There was no significant difference in postoperative BC between the short limb and the routine limb in children with living donor liver transplantation.

Characteristics of living liver donors in a national referral hospital in Indonesia: a 13-year experience with living donor liver transplantation.

Hepatocellular carcinoma and biliary atresia lead to end-stage liver disease, which requires liver transplantation and is linked to increased mortality. Dr. Cipto Mangunkusumo Hospital is the national referral center in Indonesia and is the only center that routinely performs living donor liver transplantation (LDLT). This study presents the characteristics of living liver donors (LLDs) in Indonesia. Using the LDLT registry, we conducted a retrospective analysis of all approved donors from 2010 to 2022. The variables included clinical characteristics of the donors, graft types, and intraoperative and postoperative characteristics. The LDLT rate has increased from 5.8 to 8.8 procedures/year in the last 8 years. The average age of the 76 LLDs was 31.8 years. They were predominantly female (59%) and lived within a family relationship (90%). Pediatric LDLT was more frequent than adult LDLT (88% vs. 12%, respectively). Most grafts (86%) were obtained by left lateral sectionectomy, with a median ratio of remnant liver volume to total liver volume of 79.5% (range, 47.7%-85.8%) and a mean graft-to-recipient weight ratio of 2.65%±1.21%. The median intensive care unit length of stay (LOS) was 2 days (range, 1-5 days) and the total hospital LOS was 7 days (range, 4-28 days). The complication rate was 23%. No donor mortality was reported. LDLT in Indonesia has increased over the years. The shortage of donors for adult-to-adult liver transplantation is due to cultural differences and challenges in finding eligible donors. This study aims to explain the eligibility criteria of LLDs and contribute to creating a national policy.

Improving Safety in Living Liver Donation: Lessons From Intraoperative Adverse Events in 438 Donors Undergoing a Left Liver Resection.

Donor safety is paramount in living organ donation. Left liver resections are considered safer than right lobe hepatectomies. However, unexpected intraoperative adverse events (iAEs), defined as any deviation from the ideal intraoperative course, can also occur during left liver resections and may be life threatening or lead to postoperative complication or permanent harm to the donor and recipient. Records of 438 liver living donors (LDs) who underwent 393 left lateral sectionectomies (LLSs) and 45 left hepatectomies (LHs) between July 1993 and December 2018 in a pediatric living-donor liver transplantation center were reviewed for the appearance of iAEs that could have influenced the donor morbidity and mortality and that could have contributed to the improvement of the LD surgical protocol. Clinical characteristics of LLS and LH groups were comparable. Nine iAEs were identified, an incidence of 2%, all of them occurring in the LLS group. Seven of them were related to a surgical maneuver (5 associated with vascular management and 2 with the biliary tree approach). One iAE was associated with an incomplete donor workup and the last with drug administration. Each iAE resulted in subsequent changes in the surgical protocol. Donor outcome was at risk by 5 iAEs classed as type a, recipient outcome by 2 iAEs (type b) and both by 2 iAEs (type c). Postoperative complications occurred in 87 LDs (19.9%), with no differences between the LLS and LH groups (P = 0.227). No Clavien-Dindo class IVa or b complications or donor mortality (Clavien-Dindo class V) were observed. iAEs debriefings induced changes in our LD protocol and may have contributed to reduced morbidity and zero mortality. iAEs analysis can be used as a quality and safety improvement tool in the context of LD procedures, which may include right liver donation, laparoscopic, and robotic living liver graft procurement.

The role of portal hemodynamics in pediatric living donor liver transplantation.

The role of portal hemodynamics in pediatric living donor liver transplantation.

Risk factors for postreperfusion syndrome during living donor liver transplantation in paediatric patients with biliary atresia: a retrospective analysis

BackgroundLiving donor liver transplantation (LT) is the main treatment for paediatric biliary atresia (BA) in Asia. During LT, a series of haemodynamic changes often occur during LT reperfusion, which is...

Successful Anesthetic Management of Pediatric Living Donor Liver Transplantation with Hepatopulmonary Syndrome and Pulmonary Arteriovenous Fistula due to Biliary Atresia: A Case Report

Successful Anesthetic Management of Pediatric Living Donor Liver Transplantation with Hepatopulmonary Syndrome and Pulmonary Arteriovenous Fistula due to Biliary Atresia: A Case Report

Successful living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma: a case report

BackgroundNeuroblastoma is the most common extracranial solid tumor in childhood. Stage 4S neuroblastoma is a unique subset of neuroblastoma characterized by a favorable course and potentially low malignancy with a high rate of spontaneous tumor regression. However, recent reports have shown that there is a subgroup of patients with stage 4S neuroblastoma characterized by MYCN amplification, chromosomal aberrations, age of < 2 months at diagnosis, and significantly poorer outcomes.Case presentationA 1-month-old male infant with a huge abdominal tumor was transferred to our hospital and diagnosed with stage 4S neuroblastoma. The patient showed respiratory distress due to abdominal compartment syndrome secondary to massive hepatic invasion, and he required a silo operation and mechanical ventilation. After chemotherapy using carboplatin and etoposide, the infiltrative massive hepatic invasion was resolved and the abdominal compartment syndrome gradually improved; however, liver dysfunction as evidenced by hyperbilirubinemia, coagulopathy, and hyperammonemia continued. At the age of 3 months, living-donor liver transplantation was performed for treatment of sustained liver failure using a reduced lateral segment graft from the patient’s father. Post-transplant liver function recovered immediately. Examination of the explanted liver demonstrated that the majority of liver tissue had been replaced by fibroblastic cells after massive hepatocyte dropout. There were only small areas of residual neuroblastoma cells in the liver specimen. The patient was discharged from the hospital 5 months after transplantation with home intermittent respiratory support. At the time of this writing (23 months after liver transplantation), he was in good condition with no signs of recurrence of neuroblastoma.ConclusionsWe have herein presented a case of successful pediatric living-donor liver transplantation for sustained liver failure even after resolution of infiltrative massive hepatic invasion of stage 4S neuroblastoma. Our case clearly shows that liver transplantation can be added as an appropriate extended treatment option for liver failure after resolution of stage 4S neuroblastoma.

Optimal graft size in pediatric living donor liver transplantation: How are children different from adults?

Pediatric liver transplantation is an established treatment for end-stage liver disease in children. However, it is still posing relevant challenges, such as optimizing the graft selection according to the recipient size. Unlike adults, small children tolerate large-for-size grafts and insufficient graft volume might represent an issue in adolescents when graft size is disproportionate. Graft-size matching strategies over time were examined in pediatric liver transplantation. This review traces the measures/principles put in place to prevent large-for-size or small-for-size grafts in small children to adolescents with a literature review and an analysis of the data issued from the National Center for Child Health and Development, Tokyo, Japan. Reduced left lateral segment (LLS; Couinaud's segment II and III) was widely applicable for small children less than 5 kg with metabolic liver disease or acute liver failure. There was significantly worse graft survival if the actual graft-to-recipient weight ratio (GRWR) was less than 1.5% in the adolescent with LLS graft due to the small-for-size graft. Children, particularly adolescents, may then require larger GRWR than adults to prevent small-for-size syndrome. The suggested ideal graft selections in pediatric LDLT are: reduced LLS, recipient body weight (BW) < 5.0 kg; LLS, 5.0 kg ≤ BW < 25 kg; left lobe (Couinaud's segment II, III, IV with middle hepatic vein), 25 kg ≤ BW < 50 kg; right lobe (Couinaud's segment V, VI, VII, VIII without middle hepatic vein), 50 kg ≤ BW. Children, particularly adolescents, may then require larger GRWR than adults to prevent small-for-size syndrome. Age-appropriate and BW-appropriate strategies of graft selection are crucial to secure an excellent outcome in pediatric living donor liver transplantation.