Nutrition in pediatric end-stage liver disease.

PURPOSE OF REVIEW: The aim of this review is to outline recent studies relating to nutritional status and outcomes in pediatric end-stage liver disease. MAIN FINDINGS: Pediatric patients with chronic and end-stage liver disease are at high risk of malnutrition. Given additional growth demands in children and the inherent complications of chronic liver disease, achieving adequate nutrition in these patients remains a challenge. In addition, while guidelines on nutrition in chronic liver disease exist, global approaches and definitions of malnutrition vary. Recent literature has focused on sarcopenia and nutrition-related transplant outcomes, with some studies exploring nutritional assessment and management. Pediatric studies however continue to lag adult research, with limited prospective and interventional studies. SUMMARY: Optimizing nutrition in pediatric end-stage liver disease remains a challenge, however understanding of the mechanisms and clinical manifestations of malnutrition in this population is improving. Despite these efforts, high quality studies to determine optimal nutrition strategies and interventions are lacking behind adult evidence and should be the focus of future research.

Interplay of Donor-Recipient Relationship and Donor Race in Living Liver Donation in the United States.

INTRODUCTION: Living liver donation improves survival of end-stage liver disease (ESLD) patients. Yet, it continues to represent a small proportion of United States (U.S.) liver transplantation with existing racial disparities. We investigated the interplay of donor-recipient relationship and donor race to understand donor subgroups with no significant increase. METHODS: We studied 4407 living liver donors in the U.S. from January 1, 2012, to December 31, 2022 (median age = 36 years, and 59% were biologically related to the recipient). We quantified the change in the number of donors per 3-year increment using negative binomial regression (incidence rate ratio [IRR]), stratified by donor-recipient relationship and race/ethnicity. RESULTS: Among biologically related donors, the observed annual number of White donors increased from 146 to 253, Hispanic donors from 18 to 53, and Black donors decreased from 11 to 10. Among unrelated donors, White donors increased from 65 to 221, Hispanic donors from 4 to 25, and Black donors from 3 to 11. For the IRR of biologically related donors aged <40 and ≥40 years, White donors increased by 18% and 22%; Hispanic donors increased by 25% and 54%; and Black donors did not change. Likewise, the IRR of unrelated donors aged <40 and ≥40 years, White donors increased by 48% and 55%; Hispanic donors increased by 52% and 65%; and Black donors did not change. CONCLUSIONS: While biologically related donors represent the majority of donors, unrelated donors have substantially risen in recent years, primarily driven by White donors. Although the rate of unrelated donations increased among Hispanic donors, the absolute number remains very small (≤25 donors/year). Interventions are needed to increase education among Hispanic and Black communities to grow unrelated living liver donations across race/ethnicity.

[Infections and liver cirrhosis]. / Infektionen und Leberzirrhose.

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.

Comparing body composition measures in children with end stage liver disease using noninvasive bioimpedance analysis.

BACKGROUND: Chronic liver disease (CLD) in children, often leads to cirrhosis and end-stage liver disease (ESLD). CLD poses significant challenges in management and prognosis. Assessing body composition, including sarcopenia, is increasingly recognized as important in understanding outcomes in this population. METHODS: We conducted a prospective observational study, involving children aged 2 to 18 years with ESLD awaiting liver transplantation. Socio-demographic, clinical, and laboratory data were collected, and body composition was assessed using Bioelectrical Impedance Analysis (BIA). Sarcopenia was defined using age-specific cut-off points for appendicular skeletal muscle mass (aSMM) and fat-free mass (FFM). RESULTS: The study included 57 children (42.1% girls, 57.9% boys; median age: 10.9 years) with liver cirrhosis. Of them 11 (19.3%) died during the study. The mean duration of living with end-stage liver disease prior to participation was 5.43 years [IQR: 3.32, 8.39]. The most common etiology was biliary atresia (24.6%), followed by cryptogenic (22.8%). Deceased children exhibited significantly higher sarcopenia prevalence, lower basal metabolic rate and growth scores compared to survivors (P < 0.05), (771.0 vs. 934.0, P = 0.166) (65.0 vs. 80.5, P = 0.005). Total body and limb-specified lean mass were lower in deceased children, although not statistically significant. Similarly, total mineral (90% normal) and bone mineral content were lower in deceased children, with a significant difference observed only in water-to-FFM percentage (72.5 vs. 73.1, P = 0.009). CONCLUSION: This study highlights the high prevalence of sarcopenia among children with ESLD and its association with adverse outcomes, including mortality. Bioimpedance analysis emerges as a promising, non-invasive method for assessing body composition in pediatric ESLD, warranting further investigation and integration into clinical practice.

The Predictive Value of the MELD Scores for In-Hospital Adverse Events in Normotensive Patients with Acute Pulmonary Embolism.

The model for end-stage liver disease (MELD) and the model for end-stage liver disease excluding international normalized ratio (INR) (MELD-XI) scores, which reflect dysfunction of liver and kidneys, have been reported to be related to the prognosis of patients with right-sided "backward" failure. However, the relationship between the MELD/MELD-XI score and the in-hospital adverse events in pulmonary embolism (PE) patients was unknown. Normotensive PE patients were retrospectively enrolled at China-Japan friendship hospital from January 2017 to February 2020. The primary outcome was defined as death and clinical deterioration during hospitalization. Multivariate logistic analysis was used to explore the association between the MELD and MELD-XI scores for in-hospital adverse events. We also compared the accuracy of the MELD, MELD-XI, and the pulmonary embolism severity index (PESI) score using the time-dependent receiver operating characteristic curve and corresponding areas under the curve (AUC). A total of 222 PE patients were analyzed. Logistic regression analysis showed that the MELD score was independently associated with in-hospital adverse events (odds ratio = 1.115, 95% confidential interval = 1.022-1.217, P = .014). The MELD score has an AUC of 0.731 and was better than PESI (AUC of 0.629) in predicting in-hospital adverse events. Among PE patients with normal blood pressure on admission, the MELD score was associated with increased in-hospital adverse events.

A retrospective study investigating the risk of graft loss in living donor liver transplant cases where size mismatching is predicted from graft-to-recipient weight ratio.

BACKGROUND/PURPOSE: Living donor liver transplantation (LDLT) is vital for pediatric end-stage liver disease due to organ shortages. The graft-to-recipient weight ratio (GRWR) preoperatively measured predicts the outcomes of LDLT. We typically target between 0.8 and 3.0-4.0%, but the ideal GRWR remains controversial. We compared the outcomes of LDLT according to the GRWR to examine whether the criteria could be expanded while ensuring safety. METHODS: We retrospectively reviewed 99 patients who underwent LDLT in our department by dividing them into three groups according to their GRWR: Group S, with GRWR values lower than the normal range (GRWR < 0.8%); Group M, with GRWR values in the normal range (GRWR ≥ 0.8 to < 3.5%); and Group L, with GRWR values above the normal range (GRWR ≥ 3.5%). RESULTS: In Groups S and L, 46.2 and 44.4% of patients underwent splenectomy and delayed abdominal wall closure, respectively. After these intraoperative adjustments, there were no significant differences between the groups in 5-year patient survival, 5-year graft survival, or the occurrence of post-transplantation thrombosis. CONCLUSION: When the GRWR is beyond the normal threshold, the risk of complications associated with graft size might be reduced by adjustments to provide appropriate portal blood flow and by delayed abdominal wall closure.

Risk factors associated with blood transfusion in liver transplantation.

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10FIBTEM measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored.Trial register: European Clinical Trials Database (EudraCT 2018-002,510-13) and ClinicalTrials.gov (NCT01539057).

Intrinsic or Nonintrinsic End-stage Liver Disease and Its Association With Thromboelastography-based Coagulation States in Patients Undergoing Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Perioperative coagulation management in liver transplantation recipients is challenging. Viscoelastic testing with rotational thromboelastography (TEG) can help quantify hemostatic profiles. The current work aimed to investigate whether the etiology of end-stage liver disease, pretransplant disease severity, or pretransplant thrombotic or bleeding complications are associated with specific TEG patterns. DESIGN: Retrospective cohort study. SETTING: Single quaternary care hospital. PARTICIPANTS: A total of 1,078 adult liver transplant patients. INTERVENTIONS: The primary exposure was the etiology of end-stage liver disease classified as either intrinsic or nonintrinsic (eg, biliary obstruction or cardiovascular). Secondary exposures were patients' preoperative Model for End-Stage Liver Disease (MELD) score, Child-Pugh class, presence of major preoperative thrombotic complications, and major bleeding complications. MEASUREMENTS AND MAIN RESULTS: Patients with intrinsic liver disease (84%) showed higher odds of hypocoagulable (odds ratio [OR]: 3.70, 95% confidence interval [CI]: 1.94-7.07, p < 0.0001) and mixed TEG patterns (OR: 4.59, 95% CI: 2.07-10.16, p = 0.0002) compared with those with nonintrinsic disease. Increasing MELD scores correlated with higher odds of hypocoagulable (OR: 1.14, 95% CI: 1.08-1.19, p < 0.0001) and mixed TEG patterns (OR: 1.08, 95% CI: 1.03-1.14, p = 0.0036). Child-Pugh class C was associated with higher odds of hypocoagulable (OR: 8.55, 95% CI: 3.26-22.42, p < 0.0001) and mixed patterns (OR: 12.48, 95% CI: 3.89-40.03, p < 0.0001). Major preoperative thrombotic complications were not associated with specific TEG patterns, although an interaction with liver disease severity was observed. CONCLUSIONS: Liver transplantation candidates with intrinsic liver disease tend to exhibit hypocoagulable TEG patterns, while nonintrinsic disease is associated with hypercoagulability. Increasing end-stage liver disease severity, as evidenced by increasing MELD scores and higher Child-Pugh classification, was also associated with hypocoagulable TEG patterns.

Validation of MELD3.0 in 2 centers from different continents.

BACKGROUND: MELD3.0 has been proposed to stratify patients on the liver transplant waiting list (WL) to reduce the historical disadvantage of women in accessing liver transplant. Our aim was to validate MELD3.0 in 2 unique populations. METHODS: This study is a 2-center retrospective cohort study from Toronto, Canada, and Valencia, Spain, of all adults added to the liver transplant WL between 2015 and 2019. Listing indications whose short-term survival outcome is not adequately captured by the MELD score were excluded. All patients analyzed had a minimum follow-up of 3 months after inclusion in the WL. RESULTS: Six hundred nineteen patients were included; 61% were male, with a mean age of 56 years. Mean MELD at inclusion was 18.00 ± 6.88, Model for End-Stage Liver Disease Sodium (MELDNa) 19.78 ± 7.00, and MELD3.0 20.25 ± 7.22. AUC to predict 90-day mortality on the WL was 0.879 (95% CI: 0.820, 0.939) for MELD, 0.921 (95% CI: 0.876, 0.967) for MELDNa, and 0.930 (95% CI: 0.888, 0.973) for MELD3.0. MELDNa and MELD3.0 were better predictors than MELD (p = 0.055 and p = 0.024, respectively), but MELD3.0 was not statistically superior to MELDNa (p = 0.144). The same was true when stratified by sex, although the difference between MELD3.0 and MELD was only significant for women (p = 0.032), while no statistical significance was found in either sex when compared with MELDNa. In women, AUC was 0.835 (95% CI: 0.744, 0.926) for MELD, 0.873 (95% CI: 0.785, 0.961) for MELDNa, and 0.886 (95% CI: 0.803, 0.970) for MELD3.0; differences for the comparison between AUC in women versus men for all 3 scores were nonsignificant. Compared to MELD, MELD3.0 was able to reclassify 146 patients (24%), the majority of whom belonged to the MELD 10-19 interval. Compared to MELDNa, it reclassified 68 patients (11%), most of them in the MELDNa 20-29 category. CONCLUSIONS: MELD3.0 has been validated in centers with significant heterogeneity and offers the highest mortality prediction for women on the WL without disadvantaging men. However, in these cohorts, it was not superior to MELDNa.

Relationship between updated MELD and prognosis in alcohol-associated hepatitis: Opportunities for more efficient trial design.

BACKGROUND: Alcohol-associated hepatitis (AH) is associated with significant mortality. Model for End-Stage Liver Disease (MELD) score is used to predict short-term mortality and aid in treatment decisions. MELD is frequently updated in the course of AH. However, once the most updated MELD is known, it is uncertain if previous ones still have prognostic value, which might be relevant for transplant allocation and trial design. We aimed to investigate the predictive performance of updated MELDs in a prospectively collected cohort of patients with AH by the InTeam consortium. METHODS: Three hundred seven patients (with 859 MELD values within 60 d of admission) fulfilled the inclusion criteria. The main endpoint was time to death or transplant up to 90 days. We used a joint model approach to assess the predictive value of updated MELDs. RESULTS: Updated MELD measurements had a strong prognostic value for death/transplant (HR: 1.20, 95% CI: 1.14-1.27) (p < 0.0001). Previous MELD values did not add predictive value to the most current MELD. We also showed that MELD at day 28 (MELD28) had a significant predictive value for subsequent mortality/transplant in a landmark analysis (HR: 1.18, 95% CI: 1.12-1.23). We show that the use of an ordinal scale including death, transplant, and MELD28 as a trial outcome could substantially reduce the sample size required to demonstrate short-term benefit of an intervention. CONCLUSION: We show that updated MELDs during the trajectory of AH predict subsequent mortality or the need for transplant. MELD28 inclusion in an ordinal outcome (together with death or transplant) could increase the efficiency of randomized controlled trials.

Does body weight below 6 kg modify survival of infants after liver transplant? Complete National Transplant Registry Data.

OBJECTIVE: To determine the impact of infant recipient body weight at primary liver transplantation (LT) on both recipient and graft survival rates in complete national data from Poland. METHODS: We conducted a single-center, retrospective cohort study including 142 LT recipients below 1 year of age with body weights below 10 kg who received primary and isolated LT between 2001 and 2017. Patients were divided into two study groups according to body weight at the time of LT: (1) Group I (≤6.0 kg, 32 patients) and (2) Group II (6.1-9.9 kg, 110 patients). Independent impact of body weight on patient and graft survival were assessed using survival curves and a multivariable Cox regression analysis. The univariate predictors of mortality or retransplantation at 1 year post-LT were recipient body weight of ≤6 kg at transplantation, pediatric end-stage liver disease score, urgent LT, graft from deceased donor, cold ischemia time, post-LT hepatic artery thrombosis, and post-LT dialysis. RESULTS: No statistically significant impact of body weight ≤6 kg on 1-year failure-free survival was found based on the multivariable analysis (p = 0.063). Body weight ≤6 kg was associated with longer post-LT intensive care unit and post-LT hospital stays (p = 0.013 and 0.025, respectively). CONCLUSIONS: Since no evidence of independent negative impact of recipient body weight ≤6 kg on failure-free survival 1 year post-LT was found, LT in infants with end-stage liver disease in Poland should be performed according to medical indications and urgency when an appropriate donor is available.

Palliative care and end stage liver disease: A survey study comparing perspectives of hepatology and palliative care physicians and clinical scenarios that could require palliative care intervention.

BACKGROUND AND AIMS: The prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention. METHODS: A cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years). RESULTS: A total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered "rare" by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity. CONCLUSION: The current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

En Bloc Simultaneous Liver-Kidney Transplantation Compared to the Traditional Technique: Results From a Single Center.

BACKGROUND: Simultaneous liver-kidney transplantation is indicated for patients with concomitant end-stage liver disease and end-stage renal disease. The traditional technique involves separate implantations of the liver and the kidney. In the en bloc approach, the liver is recovered en bloc with the right kidney and the donor renal artery is anastomosed to the donor splenic artery. We aimed to compare the outcomes of the traditional and en bloc techniques for simultaneous liver-kidney transplantation in a single center. METHODS: This single-center retrospective study involved all adult patients who underwent simultaneous liver-kidney transplantation from brain-dead donors from January 2017 to December 2022. RESULTS: A total of 15 patients were included: 10 transplanted with the traditional technique and 5 with the en bloc approach. Patients in the en bloc group presented higher body mass index, shorter kidney cold and total ischemia times, shorter overall surgical time and longer kidney warm ischemia time (29.07 kg/m2vs 23.20 kg/m2 [P = .048]; 560 minutes vs 880 minutes [P = .026]; 615 minutes vs 908 minutes [P = 0.025]; 405 minutes vs 485 minutes [P = .046]; 46 minutes vs 33.5 minutes [P = 0.027], respectively). Ureteroneocystostomy was performed in 2 patients of the en bloc group and ureteroureterostomy in the remaining 3 patients. One patient in the en bloc group presented stenosis of renal artery anastomosis and underwent percutaneous angioplasty. This same patient eventually developed late urinary fistula. In the traditional technique group, there were 2 cases of renal vein thrombosis and 1 of ureteral stenosis. CONCLUSIONS: Compared with the traditional technique, the en bloc approach is feasible and safe, reducing kidney total ischemia time and overall surgical time.

Burden of Portal Hypertension Complications Is Greater in Liver Transplant Wait-Listed Registrants with End-Stage Liver Disease and Type 2 Diabetes.

BACKGROUND AND AIMS: Impact of type 2 diabetes mellitus (T2DM) in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT) remains poorly defined. The objective of the present study is to evaluate the relationship between T2DM and clinical outcomes among patients with LT waitlist registrants. We hypothesize that the presence of T2DM will be associated with worse clinical outcomes. METHODS: 593 patients adult (age 18 years or older) who were registered for LT between 1/2010 and 1/2017 were included in this retrospective analysis. The impact of T2DM on liver-associated clinical events (LACE), survival, hospitalizations, need for renal replacement therapy, and likelihood of receiving LT were evaluated over a 12-month period. LACE was defined as variceal hemorrhage, hepatic encephalopathy, and ascites. Kaplan-Meier and Cox regression analysis were used to determine the association between T2DM and clinical outcomes. RESULTS: The baseline prevalence of T2DM was 32% (n = 191) and patients with T2DM were more likely to have esophageal varices (61% vs. 47%, p = 0.002) and history of variceal hemorrhage (23% vs. 16%, p = 0.03). The presence of T2DM was associated with increased risk of incident ascites (HR 1.91, 95% CI 1.11, 3.28, p = 0.019). Patients with T2DM were more likely to require hospitalizations (56% vs. 49%, p = 0.06), hospitalized with portal hypertension-related complications (22% vs. 14%; p = 0.026), and require renal replacement therapy during their hospitalization. Patients with T2DM were less likely to receive a LT (37% vs. 45%; p = 0.03). Regarding MELD labs, patients with T2DM had significantly lower bilirubin at each follow-up; however, no differences in INR and creatinine were noted. CONCLUSION: Patients with T2DM are at increased risk of clinical outcomes. This risk is not captured in MELD score, which may potentially negatively affect their likelihood of receiving LT.

Factors Associated With Recurrence of Underlying Diseases Among Liver Transplant Recipients: A Single-Center Study.

OBJECTIVES: The recurrence of underlying diseases remains a major cause of graft failure after liver transplant. This study aimed to identify factors associated with the recurrence of underlying diseases and investigate the incidence of these factors and recurrence at the main liver transplant center in Iran. MATERIALS AND METHODS: We included adult liver transplant recipients followed at Shiraz Transplant Center between 2011 and 2018 with a confirmed diagnosis of recurrence of underlying disease in our study. We reviewed medical records and extracted data on demographic characteristics, clinical and paraclinical features, medication use, and current status. We used a systematic random sampling method to select a control group of 95 transplant recipients who did not have recurrence. Of 3022 total transplant recipients, 76 recipients experienced a recurrence of their underlying disease. RESULTS: Model for End-Stage Liver Disease score, underlying disease, recipient blood group, donor sex, donor blood group, and rejection frequency were significantly different between study groups with and without recurrence of underlying diseases. Liver transplant recipients with recurrence had lower mean Model for End-Stage Liver Disease score. Recipients with recurrence also had higher rate of drug consumption (eg, prednisolone, tacrolimus, mycophenolate mofetil, sirolimus). Regression analysis showed that donor sex and rejection frequency had an effect on disease recurrence. Death occurred more frequently in liver transplant recipients with recurrence than in the control group (39.5% vs 26.3%), butthe difference was not significant. CONCLUSIONS: Donor sex and acute rejection frequency are independent factors predictive of the recurrence of underlying disease. Modifying risk factors can help minimize the recurrence of underlying diseases after liver transplant.

Modified by the Innovative Drugs and Strategies-Pattern of Selected Indications for Pediatric Liver Transplantation.

BACKGROUND: Liver transplantation (LTx) constitutes a major life-saving routine treatment for children with end-stage liver disease. However, the analysis of LTx registries in children provides much information about changes in the indication profiles in the recent years. METHODS: The article provides a comprehensive review about the successes, hopes, and challenges related to changing indications for LTx in children based on the literature review and our own experience. Retrospective review of the indications for LTx at a tertiary referral pediatric hospital was also presented. RESULTS AND CONCLUSIONS: In the context of the new therapies that have emerged, the need for LTx has decreased in patients with chronic hepatitis B and C infection and tyrosinemia type 1. In primary hyperoxaluria type 1, new RNAi-based therapy has eliminated the requirement for LTx (both isolated or combined). There is a hope that introduction of ileal bile acid transporter (IBAT) blockers reduces the need for LTx in patients with Alagille syndrome or progressive familial intrahepatic cholestasis. The number of children qualified for LTx with urea cycle disorders (UCDs) as a prophylaxis of neurodevelopmental impairment is increasing.