Pediatric End-stage Liver Disease Research Articles

Evaluation of Vitamin D Levels in Children With Liver Transplant.

Vitamin D deficiency is common in pediatric chronic liver disease despite oral replacement. We evaluated vitamin D deficiency before and after liver transplant and the relationship between posttransplant and pretransplant vitamin D deficiency and graft rejection. Pediatric recipients with chronic liver disease (N =138) were divided into 4 groups: cholestatic liver diseases, cirrhosis, metabolic disorders, and acute liver failure. Pretransplant and posttransplant vitamin D levels, liver function tests, Pediatric End-Stage Liver Disease scores, rejection activity index scores by graft liver biopsy, and posttransplant patient survival were recorded. There were 62 (45%) female and 76 (55%) male participants (mean transplant age, 6.1 ± 5.6 years). Pretransplant mean available vitamin D of 90 patients was 25.2 ± 20.9 ng/mL, with 36 (40%) within reference range. Posttransplant level for 109 patients was 27.3 ± 18 ng/mL, with 64 (58.7%) within reference range. Pretransplant and posttransplant levels were available for 61 patients, and mean pretransplant levels were lower than posttransplant levels (23.7 ± 19.3 vs 28.3 ± 16.9 ng/mL; P = .01). Patients with cholestatic liver disease had lower pretransplant vitamin D levels (P = .04), which disappeared after transplant. Pretransplant vitamin D levels were positively correlated with serum albumin levels (r = 0.20) in all patients and negatively correlated with total/direct bilirubin (r = 0.29 and r = -0.30) in those with liver diseases and cirrhosis. No correlations were found between pretransplant vitamin D levels and Pediatric End-Stage Liver Disease scores, rejection activity index scores, and posttransplant mortality. Vitamin D deficiency is prevalent in pediatric chronic liver disease before and after transplant, especially for cholestatic liver diseases. However, no association between vitamin D levels and liver graft rejection or patient survival was noted. We recommend close monitoring and individualized vitamin D supplementation before and after liver transplant.

Comparison of Liver Transplant Outcomes in Biliary Atresia Patients, Considering Whether They Underwent the Kasai Procedure Beforehand: A Single Center Analysis of 72 Patients

This study examines the results of liver transplantation (LT) in patients with biliary atresia, considering whether they underwent the Kasai procedure beforehand. LT and determine postoperative and long-term graft outcomes. This single-center, retrospective study included 72 pediatric patients diagnosed with postpartum biliary atresia who underwent LT between 2010 and 2022. We included patients who underwent LT either after or without the Kasai procedure and compared the demographic data of the patients with various factors, such as the Pediatric End-Stage Liver Disease scores and laboratory values. The study included 72 patients, with 39 of them being female (54.2%) and 33 of them being male (45.8%). Of the 72 patients in the study, 47 (65.3%) had undergone the Kasai procedure, and 25 (34.7%) had not. The preoperative and postoperative month 1 bilirubin values were lower in patients who underwent the Kasai procedure and were higher in postoperative months 3 and 6. Preoperative bilirubin values, postoperative month 3 bilirubin values, and preoperative albumin values were higher in patients who developed mortality (P < .05). Cold ischemia time was longer in patients who developed mortality (P < .05). Our study showed a higher mortality rate in patients who underwent the Kasai procedure. The results also showed that LT was more effective in children, as patients with Kasai had higher mean bilirubin values and higher preoperative albumin values than patients without Kasai.

The Factors Affecting Mortality After Pediatric Liver Transplantation and Long-Term Survival Outcomes: A Single Center Experience

BackgroundLiver transplantation (LT) is a treatment modality in the pediatric population for several diseases like biliary atresia, metabolic liver disease, hepatoblastoma, and so on. According to the Organ Procurement and Transplantation Network, 5-year survival was reported as 85.4% to 93.5% by age after pediatric liver transplantation (PLT). This study aimed to evaluate our single-center experience of PLT by analyzing long-term results, comparing the outcomes with the literature, and identifying predictors of patient survival. MethodsThe data of 40 patients who underwent LT at <18 years of age between June 2015 and June 2021 were studied retrospectively. Recipient characteristics such as age, sex, etiology of liver disease follow-up time, postoperative vascular and biliary complications, and donor characteristics were evaluated. ResultsThere were 20 (50%) girls and 20 (50%) boys, and the median age was 42 (IQR = 9-117) months. The most common indications of LT were biliary disorders (45%). A whole liver graft was used in 7 (17%), a right lobe graft in 9 (23%), a left lobe graft in 4 (10%), and a left lateral lobe graft in 20 (50%) of the recipients. The 1-, 3-, 5-, and 7-year survival rates were 85%, 82.1%, 82.1%, and 82.1%, respectively. The multivariate survival analysis revealed that the pediatric end-stage liver disease score, hepatic artery thrombosis, and portal vein thrombosis are associated with overall mortality. ConclusionIn conclusion, our long-term survival is similar to the literature, with satisfactory results. However, reducing the vascular complication rates can provide superior results on PLT.

Socio-economic issues in the diagnostic approach and decision to treat of a child with familial cholestasis

Objectives. The diagnostic approach in familial cholestasis cases involves using expensive investigations. The need for complex therapeutic resources is predictable. Material and methods. We present the case of a 3 years 5 months old boy diagnosed with cholestasis and liver cirrhosis, admitted in the Pediatrics Department of “Grigore Alexandrescu” Children’s Hospital for evaluation in order to check the criteria for liver transplantation. Outcomes. The patient is known to our clinic since he was 1 year 3 months; he was admitted at that time for green jaundice. He comes from a family with nine children, low socio-economic status and low education. The first four children have a different father, two of them were stillborn. The next five come from a consanguineous union (the father is maternal uncle of the mother): three (the patient included) presented with the same symptoms, two of them died before 3 years of age with liver cirrhosis. In time, infectious causes, autoimmune, neoplastic and metabolic disease were excluded. The liver biopsy describes cholestasis and fibrosis. Alagille syndrome and progressive familial intrahepatic cholestasis are still debated, but the genetic testing necessary for a positive diagnosis are not financially available to the family. The patient presents with failure to thrive, developmental delay, intense jaundice and pruritus, hippocratic fingers, dyspnea, enlarged abdomen with visible collateral circulation, significant hepatosplenomegaly. The lab tests show anemia, thrombocytopenia, liver cytolysis, normal gamma-glutamyl transferase, low prothrombin activity, normal renal function, no inflammatory syndrome, increased ammonia level, very high bile acids level. The upper endoscopy describes first degree esophageal varices and portal hypertensive gastropathy. A PELD (Pediatric End-Stage Liver Disease) score is calculated – 13.6 (76.3% one year survival rate on the transplant list, 90.9% one year survival rate after liver transplantation). The patient is enrolled on the transplant waiting list provided we would expect suboptimal results considering the developmental delay and difficult post-transplant monitoring. Conclusions. The low education level of the family correlated with a postponed positive diagnosis due to financial reasons and the lack of genetic advice already lead to the demise of four brothers. In this setting, the prognosis of the patient is very likely to be poor.

Fluid balance in pediatric postoperative liver transplant recipients.

Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients. We performed a retrospective cohort study of first-time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72h postoperatively: <10%, 10-20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator-free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)-III score. We included 129 patients with median PRISM-III score of 9 (interquartile range, IQR 7-15) and calculated Pediatric End-stage Liver Disease score of 15 (IQR 2-23). A total of 37 patients (28.7%) had 10-20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18-2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10-1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74-0.97). There were no differences between groups in the likelihood of postoperative complications. In pediatric LT recipients, >20% FB at 72hpostoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes.

MELD 3.0 for adolescent liver transplant candidates.

Adolescents constitute a unique waitlist cohort that is distinct from younger children. Model for End-stage Liver Disease (MELD) 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Sodium in the current liver allocation system for both adults and adolescents aged 12-17. We evaluated the predictive performance of MELD-Sodium, MELD 3.0, and Pediatric End-stage Liver Disease for 90-day waitlist mortality risk among adolescent liver transplant registrants. New waitlist registrations for primary liver transplants among individuals aged 12-17 and 18-25 for comparison were identified using Organ Procurement and Transplantation Network (OPTN) data from November 17, 2004, to December 31, 2021. The predictive performance of the current and proposed MELD and Pediatric End-stage Liver Disease scores was assessed using Harrell's concordance ( c ) statistic. There were 1238 eligible listings for adolescents aged 12-17 and 1740 young adults aged 18-25. In the adolescent group, 90-day survival was 97.8%, compared with 95.9% in those aged 18-25 (log-rank p = 0.005), with no significant differences when stratified by sex or indication. Among adolescents, increasing MELD 3.0 was associated with an increased hazard of mortality (HR=1.27, 95% CI: 1.18-1.37), and the c -statistic for 90-day waitlist survival using MELD 3.0 was 0.893 compared with 0.871 using MELD-Sodium and 0.852 using Pediatric End-stage Liver Disease. The discriminative ability of MELD 3.0 to rank adolescents according to the risk of death within 90 days was robust. Although MELD 3.0 was initially developed and validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplants.

Effect of Pre-Transplant Covid-19 Exposure on Post-Liver Transplant Clinical Outcomes

BackgroundCOVID-19 has led to an unprecedented global health crisis. This situation caused an immediate reduction in solid organ transplantation activity. This study aimed to present the follow-up results of patients with chronic liver disease who underwent liver transplantation (LT) after a history of COVID-19 infection. MethodsSociodemographic characteristics and clinicopathological data of 474 patients who underwent LT at Inonu University Liver Transplant Institute between March 11, 2020 and March 17, 2022 were prospectively recorded and analyzed retrospectively. Among these, the data of 35 patients with chronic liver disease who were found to be exposed to COVID-19 infection in the pre-LT period were analyzed for this study. ResultsThe median body mass index, Child score, and Model for end-stage liver disease/ Pediatric end-stage liver disease scores of the 35 patients were calculated as 25.1 kg/m2 (IQR: 7.4), 9 points (IQR: 4), and 16 points (IQR: 10), respectively. Graft rejection occurred in 4 patients at a median of 25 days post-transplant. Five patients underwent retransplantation at a median of 25 days post-transplant. The most common cause of retransplantation is early hepatic artery thrombosis. There were 5 deaths during postoperative follow-up. Mortality developed in 5 (14.3%) patients exposed to COVID-19 infection in the pretransplant period, whereas mortality occurred in 56 (12.8%) patients not exposed to COVID-19 infection. There was no statistically significant difference in mortality between the groups (P = .79). ConclusionsThe results of this study showed that exposure to COVID-19 before LT does not affect post-transplant patients and graft survival.

The Role of Pretransplant Infections in Pediatric Receiving LDLT in Indonesia: A 7-y Retrospective Study.

This is an observational, retrospective cohort study. A total of 56 children were recruited between April 2015 and May 2022. Patients were categorized into 2 according to the presence of pretransplantation infections requiring hospitalization before the surgery. Diagnosis of posttransplantation infection was observed for up to 1 y based on the clinical features and laboratory parameters. The most common indication for LDLT was biliary atresia (82.1%). Fifteen of 56 patients (26.7%) had a pretransplant infection, whereas 73.2% of patients were diagnosed with a posttransplant infection. There was no significant association between pretransplant and posttransplant infection in all 3-time points (≤1 mo, 2-6 mo, and 6-12 mo). The most common organ involvement posttransplantation was respiratory infections (50%). The pretransplant infection did not significantly affect posttransplant bacteremia, length of stay, duration of mechanical ventilation, initiation of enteral feeding, hospitalization cost, and graft rejection. Our data showed that pretransplant infections did not significantly affect clinical outcomes in post-LDLT procedures. A prompt and sufficient diagnosis and treatment before and after the LDLT procedure is the best way to obtain an optimal outcome.

Early relaparotomy following pediatric living-donor liver transplantation: experience in an Indonesian national referral hospital

BackgroundLiving donor liver transplantation (LDLT) remains the only curative treatment for children with end-stage liver disease; however, complications of the procedure are associated with indications for early relaparotomy. Several risk...

Home Parenteral Nutrition for Children: What Are the Factors Indicating Dependence and Mortality?

Parenteral nutrition (PN) in children with short bowel syndrome is crucial and lifesaving. Taking care of such patients requires interprofessional practice and multiple team resource management. Home PN (HPN) usage allows patients and families to live regular lives outside hospitals. We share our experiences for the last two decades and identify the risk factors for complications and mortality. A retrospective study of HPN patients was conducted between January 2000 and February 2022. Medical records of age, body weight, diagnosis, length of residual intestines, HPN period, central line attempts, complications, weaning, and survival were collected and analyzed. The patients were classified as HPN free, HPN dependent, and mortality groups. A total of 25 patients received HPN at our outpatient clinic, and one was excluded for the adult age of disease onset. There were 13 patients (54.1%) who were successfully weaned from HPN until the record-enroled date. The overall mortality rate was 20.8% (five patients). All mortality cases had prolonged cholestasis, Child Class B or C, and a positive Pediatric End-Stage Liver Disease (PELD) score. For HPN dependence, extended resection and multiple central line placement were two significant independent factors. Cholestasis, Child Class B or C, and positive PELD score were the most important risk factors for mortality. The central line-related complication rate was not different in all patient groups. The overall central line infection rate was 1.58 per 1000 catheter days. Caution should be addressed to prevent cholestasis and intestinal failure-associated liver disease during the HPN period, to prevent mortality. By understanding the risks of HPN dependence and mortality, preventive procedures could be addressed earlier.

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Duration of Invasive Mechanical Ventilation Post-Liver Transplantation: Does One Size Fit All?

Extracorporeal Therapies in Children with Acute Liver Failure: A Single-Center Experience.

The aim of this study is to determine the indication, timing, and administration of extracorporeal therapies such as total plasma exchange and continuous renal replacement therapy in children with acute liver failure or acute-on-chronic liver failure. This study is conducted as a retrospective, single-center study. Between January 2016 and December 2021, pediatric acute liver failure or acute-on-chronic liver failure patients for whom total plasma exchange and/or continuous renal replacement therapy was performed were included in this study. Thirty-four children with acute liver failure or acute-on-chronic liver failure were included during the study period. The children comprised 14 (41.1%) males, and the median age of the patients was 54 months (5-21). Twenty-four patients (70.6%) had pediatric acute liver failure, and 10 patients (29.4%) had acute-on-chronic liver failure. Patients' median model for end-stage liver disease and pediatric end-stage liver disease scores were 24.7/23.5, respectively. Total plasma exchange therapy was performed on all patients whereas continuous renal replacement therapy was performed on 13 patients (38.2%). The median duration of continuous renal replacement therapy was 2.5 days (2-24). The median number of the total plasma exchange sessions was 3 (1-20). The median length of stay in pediatric intensive care unit was 4.5 (2-74) days. Eleven (32.5%) patients had 1 or more improvements in hepatic encephalopathy scores after extracorporeal therapy. Eleven (32.5%) patients died. There was a significant difference between the survivors and non-survivors with respect to levels of albumin, ammonia, pediatric risk of mortality scores, and pre-hepatic encephalopathy scores. Liver transplantation was performed in 4 of 24 pediatric acute liver failure patients, and all of them survived. Total plasma exchange and continuous renal replacement therapy are life-saving, and both methods may reduce morbidity and mortality, also bridging to liver transplantation.

Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation.

Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.

Early period intensive care follow-up after liver transplantation in children: a single center experience.

Liver transplantation (LT) is a well-established, life-saving treatment for children with irreversible acute and chronic liver failure (LF). We aimed to evaluate the factors associated with morbidity and mortality in the early period of LT in children by reviewing our pediatric intensive care unit (PICU) experience. We reviewed children`s medical records followed in the PICU after LT between May 2015-August 2021, including demographic parameters, indications for LT, operative variables, respiratory and circulatory support requirements, LT-related complications and survival. During this period, 40 pediatric patients who underwent LT were evaluated. LT was performed in 35 (87.5%) cases of chronic liver disease and 5 (12.5%) cases of acute liver failure. Twenty-four patients had chronic liver failure due to cholestatic liver disease. The patients` Pediatric Risk of Mortality (PRISM) III score was 18.82±SD (2-58) at PICU admission. 1-year survival was 87.5%, and overall survival was 85%. Younger age, low body weight, preoperative pediatric end-stage liver disease (PELD), and model for end-stage liver disease (MELD) values of 20 and higher were important risk factors for unfavorable outcomes after living donor liver transplantation (LDLT). These risk factors are both associated with technically more challenging vascular and bile duct reconstruction and higher complication rates, and increased mortality during the early period after LT. The early period of optimum PICU management in pediatric LT recipients is crucial for successful outcomes, which is also related to the patients` characteristics, disease severity scores, and surgical procedures.

Pediatric liver transplantation for autoimmune liver disease: Ten-year experience from a liver transplant center in India.

Liver transplantation (LT) has emerged as the best therapeutic modality for end-stage liver disease in pediatric autoimmune liver disease (AILD). We aimed to describe our experience of pediatric living donor liver transplantation for AILD from India over a period of 10 years.We did a retrospective analysis of 244 liver transplants at our center over the last 10 years to identify children with AILD (18 years or younger). We aimed to describe the demographic features, clinical profile, graft survival, patient outcome, and predictors of mortality in our cohort.Between July 2010 and May 2020, 13 liver transplants were performed for AILD out of total 244 children transplanted over the last 10 years at our center. Mean (standard deviation [SD]) age at LT was 12 (± 3.84) years. Leading indications for LT were decompensated liver disease (61.5%), acute-on-chronic liver failure (23.1%), acute liver failure (ALF) (7.7%), and recurrent cholangitis and growth failure (7.7%). Mean Pediatric End-stage Liver Disease (PELD) score/model for end-stage liver disease (MELD) score and international normalized ratio (INR) (SD) at presentation were 24 (± 12.81) and 2.48 (± 1.54), respectively. Median discharge duration was 23 days (interquartile range [IQR] 21-36 days). 30.7% (4/13) of the subjects had no postoperative complications. Diarrhea (15.3%), pneumonia (7.7%), jejunostomy site bleed (7.7%), tacrolimus toxicity (7.7%), and vascular complications (7.7%) were seen, which resolved with satisfactory graft function. Three subjects died post-LT; causes of death included sepsis (n=3), renal dysfunction (n=1), and pneumonia (n=1). Others have been well on follow-up with no graft rejection or need for re-transplantation. Overall, 1-year and 5-year patient survival rates were 76.9% and 70%, respectively. Lower platelet count, autoimmune hepatitis (AIH) 2, and PELD/MELD score were found to be significant predictors of mortality on univariate analysis, which were not significant on multivariate modelling.Thecomplications, graft and patient survival rates in our experience were quite encouraging, and are comparable with the best centers worldwide. After instituting appropriate treatment, early referral of such patients to an equipped center should be facilitated.

Posttransplant renal replacement therapy is an alarm signal for survival outcomes in pediatric liver transplantation.

The impact of renal replacement therapy (RRT) on the long-term survival outcomes of pediatric liver recipients remains controversial. A total of 224 patients aged <18 years, who underwent liver transplantation (LT), were divided into two groups: patients who underwent renal replacement therapy (RRT) (group R, n=25, 11.2%) and those who did not (group N, n=199, 88.8%). The posttransplant patient survival outcomes according to RRT use constituted the primary end-point. RRT was initiated preoperatively in 12 patients (48.0%) and postoperatively in 13 [early: <6 months after LT (n=5, 20.0%) and late: ≥6 months after LT (n=8, 32.0%)]. The indications for RRT included liver disease involving the kidney (44.0%) and hepatorenal syndrome (56.0%). The age at the time of LT (71.6 vs. 19.1 months) was higher, the pediatric end-stage liver disease score was lower (9.9 vs. 21.2), and the duration of hospitalization posttransplantation (41.0 vs. 27.0 days) was longer, while the rates of hepatic artery thrombosis (8.0% vs. 3.5%) were higher in group R (p < .05). The number of patients (60.0% vs. 93.0%; p < .001) and graft survival rates (68.0% vs. 93.0%; p < .001) were significantly lower in group R. Multivariate analysis revealed that posttransplant RRT and hepatic artery complications were risk factors for patient survival outcomes. Renal function was recovered in 7 patients (28.0%) in group R, and 9 (36.0%) eventually underwent kidney transplantation. The survival outcomes of children requiring posttransplant RRT were significantly worse than those of children, who did not undergo RRT. Physicians should pay meticulous attention to patients requiring post-LT RRT.

Finding Value in Pediatric Liver Transplantation: When Does Volume Matter?

INTRODUCTION: Pediatric liver transplantation provides substantial survival benefit. An emphasis on value-based practices has become a central theme in many surgical fields, but value-based practices have not been well studied in pediatric transplantation. Given an increasing focus on optimizing outcomes with containing costs, defining value in pediatric liver transplantation warrants investigation. METHODS: Pediatric End-stage Liver Disease (PELD) era pediatric liver transplant recipients from February 2002 to February 2019 were identified using United Network for Organ Sharing (UNOS) STAR file data (n = 5,770). Liver centers were divided into volume tertiles (small, medium, large) and recipients were stratified by age (0 to 4, 5 to 11, 12 to 18 years). Value for the index transplant episode was defined as % graft survival ≥1 year divided by mean post-transplant length-of-stay (LOS). Nearest-neighbor Mahalanobis metric matching was used to account for confounding when assessing the impact of center volume on value. RESULTS: Compared with small centers, large centers delivered better outcomes (1-year graft survival 93.7% vs 89.4%, p = 0.017) without increased resource utilization (LOS 20.8 ± 15.6 days vs 19.6 ± 17.0, p = 0.281) during the 17-year study period. Mahalanobois-matched cohorts demonstrated a volume-value relationship (higher value care with better outcomes and decreased resource utilization) in the 0 to 4 age group, but not in older recipients (Table). The 0 to 4 age group comprised the largest proportion of status 1B patients (20.8%, p < 0.001) and the highest utilization rate of partial liver allografts (40.9%, p < 0.001). CONCLUSION: There is value in liver transplant volume in very young (0 to 4 years) pediatric patients. Given improved survival of these patients in higher-volume centers, regionalization of care may benefit this specific population of recipients. Table. - Matched Comparison of Length of Stay and 1-Year Graft Survival after Liver Transplant 1-year graft survival Small (%) Large (%) p Value Pediatric 0–4 y 87.1% 94.7% 0.011 Pediatric 5–11 y 92.0% 95.9% 0.252 Pediatric 12–18 y 92.4% 90.8% 0.704 Length of stay, days Small, mean (SD) Large, mean (SD) Pediatric 0–4 y 28.29 (22.8) 22.40 (14.8) 0.003 Pediatric 5–11 y 16.05 (12.6) 18.57 (13.8) 0.182 Pediatric 12–18 y 13.67 (12.3) 19.87 (15.0) 0.003

Perspectives on Sarcopenia as a Predictor for Outcomes in Pediatric Patients with Chronic Liver Disease.

Sarcopenia, a pathologic deficiency of muscle mass and function, has emerged as an important secondary feature of many chronic disease states. For adults with end stage liver disease, there are multiple mechanisms which contribute to sarcopenia and its presence has proven to be an important predictor of morbidity and mortality. In children, there are only a limited number of reports which investigate the role of sarcopenia in liver disease. These studies, which are discussed and summarized in this review, report small, single-center analyses with dissimilar study cohorts and varying clinical definitions. Still, children meeting the study entry criteria have sarcopenia with a reported prevalence of 24–70%. When assessed, sarcopenia appears to be associated with more severe disease but is independent of the Pediatric End-Stage Liver Disease (PELD) score and does not correlate with age, gender, or traditional anthropometric measures such as weight, height, weight-for-height, or body mass index (BMI). While individual studies may identify sarcopenia as a statistically significant risk factor for certain post-transplant outcomes such as longer ICU stay, longer duration of intubation, repeat operation, development of serious infection, longer hospital stay, death, or long-term growth failure, such associations are not consistently replicated across studies. Finally, although various methods of muscle mass quantification are utilized, the most reported is the total psoas muscle surface area (tPMSA) on computed tomography. This method, along with others such as skeletal muscle area and skeletal muscle index, have had normative values recently defined and these collective efforts should enable researchers a common basis of comparison when delineating sarcopenia, and its impact, across various study populations in future investigations – including in children with liver disease.

The effect of steatotic donor livers on the prognosis of donors and recipients after pediatric living donor liver transplantation

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ2 test,or Fisher's exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.

Granulocyte colony-stimulating factor therapy as a bridging treatment for pediatric decompensated liver cirrhosis prior to liver transplantation: an open-label randomized clinical trial

Background: Decompensated cirrhosis (DC) in children is the main indication of liver transplantation (LT). The lack of access to liver transplantation and impending clinical complications while awaiting transplantation affect the morbidity and mortality in pretransplant patients. Granulocyte colony-stimulating factor (G-CSF) therapy has shown promising results in adult decompensated cirrhosis as a potential bridging treatment. Our study aimed to identify the effect of G-CSF on pediatric end-stage liver disease (PELD) score, liver function, CD34+ cell mobilization, nutritional status, survival, and short-term side effects in children awaiting LT. Methods: This study was an open-label, randomized controlled trial that included patients with decompensated liver cirrhosis between 3 months and 12 years of age. The intervention group received 12 courses of G-CSF subcutaneous injection (5 μg/kg/day) plus standard medical treatment (SMT) for liver cirrhosis. Results were obtained regarding PELD scores, liver function, CD34+ cell mobilization, changes in leukocyte and neutrophil counts, nutritional status, survival, and side effects within three months. Results: Thirty-five pediatric patients were randomized into the intervention (17 patients) and control (18 patients) groups. During the trial, 14 (82%) in the intervention group completed the treatment. The median ages of the patients in the intervention and control groups were 18 and 14.5 months, respectively. The study's primary outcome identified no statistically significant difference in PELD scores between the intervention and control groups after G-CSF treatment. Liver function tests that showed significant changes in the intervention group compared to the control group were from improvements in alanine aminotransferase (ALT) levels. Other liver function tests, nutritional status, and survival did not. CD34+ cell mobilization was increased in the intervention group compared with the control group, but there was no significant difference. Minor side effects of G-CSF were observed in the intervention group. Conclusion: Multiple doses of G-CSF did not improve the PELD score, nutritional status, and survival after three months but significantly showed temporary improvement in ALT level.