Bloodless Medicine in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) poses challenges for patients who decline blood products because of religious beliefs or other reasons. Despite potential curative prospects, many institutions refrain from offering alloHSCT to patients who decline blood products because of safety concerns associated with cytopenias.

Objectives: This review focuses on one institution's experience of conducting alloHSCT without blood components, emphasizing preparation and supportive care.

Erratum to "Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis" [JHEP Reports 6 (2024) 100949].

[This corrects the article DOI: 10.1016/j.jhepr.

Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact.

Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis.

Background & Aims: Progressive familial intrahepatic cholestasis (PFIC) relates to a group of rare, debilitating, liver disorders which typically present in early childhood, but have also been reported in adults. Without early detection and effective treatment, PFIC can result in end-stage liver disease. The aim of the paper was to put forward recommendations that promote standardisation of the management of PFIC in clinical practice.

Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression.

Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis.

Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis.

Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age).

The role of immunosuppression in long-term graft hepatitis and fibrosis after paediatric liver transplant - comparison of two treatment protocols.

Background And Aims: We have previously demonstrated high rates of chronic allograft hepatitis and fibrosis in liver transplant patients on long-term cyclosporine monotherapy. We subsequently changed practice to add low-dose prednisolone to maintenance treatment with tacrolimus post-transplant. The aim of the study was to assess the impact of the immunosuppression change on graft histopathology.

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.

Mental health providers' perceptions of competency when working with autistic children with co-occurring mental health diagnoses.

Psychotherapy research has long focused on provider competence and treatment efficacy. Mental health providers treat diverse client populations with varying, complex needs. Though estimates vary, the rate of children diagnosed with autism and a co-occurring psychiatric disorder is relatively high.

Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy.

Background And Aims: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group.

Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease.

Background And Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

Approach And Results: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.

Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a group of inherited paediatric liver diseases resulting from mutations in genes that impact bile secretion. We aimed to evaluate the effects of odevixibat, an ileal bile acid transporter inhibitor, versus placebo in children with PFIC.

Methods: Patients eligible for this 24-week, randomised, double-blind, completed, phase 3 study were paediatric outpatients diagnosed with PFIC1 or PFIC2 who had pruritus and elevated serum bile acids at screening.

Variation in Alanine Aminotransferase in Children with Non-Alcoholic Fatty Liver Disease.

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a major public health concern. Aminotransferase (ALT) is frequently used for screening and monitoring, but few studies have reported typical patterns of ALT elevation in children. Methods: TARGET-NASH is a real-world longitudinal observational cohort of patients with NAFLD receiving care across the United States.

Acute Liver Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Context: Develop evidence-based criteria for individual organ dysfunction.

Objectives: Evaluate current evidence and develop contemporary consensus criteria for acute liver dysfunction with associated outcomes in critically ill children.

Data Sources: Electronic searches of PubMed and Embase conducted from January 1992 to January 2020, used medical subject heading terms and text words to characterize acute liver dysfunction and outcomes.

Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary.

Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries.

miR-224-5p and miR-545-5p Levels Relate to Exacerbations and Lung Function in a Pilot Study of X-Linked MicroRNA Expression in Cystic Fibrosis Monocytes.

Altered microRNA expression patterns in bronchial brushings from people with versus without cystic fibrosis (CF) relate to functional changes and disease pathophysiology. The expression of microRNAs encoded on the X chromosome is also altered in peripheral blood monocytes of p. Phe508del homozygous versus non-CF individuals.

Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients.

Long-term liver transplant outcomes for progressive familial intrahepatic cholestasis type 1: The Pittsburgh experience.

Background: Progressive familial intrahepatic cholestasis type 1 (PFIC1) arises from biallelic variants in the ATP8B1 gene that annul FIC1 activity, resulting in progressive liver disease. Liver transplant (LT) is indicated in refractory disease; however, post-LT complications including worsening diarrhea and steatohepatitis progressing to fibrosis with graft loss have been reported. We aim to describe long-term outcomes of PFIC1 LT recipients at our center, focusing on the histological changes of the allografts.

Metabolic Control and "Ideal" Outcomes in Liver Transplantation for Maple Syrup Urine Disease.

Objectives: To assess outcomes following liver transplantation for maple syrup urine disease by determining attainment and sustainability of metabolic control and apply an "ideal" outcome composite in long-term survivors.

Study Design: A single center, retrospective review collected clinical data including branched-chain amino acid (leucine, isoleucine, and valine) levels following liver transplant and determined achievement of an ideal long-term outcome profile of a first allograft stable on immunosuppression monotherapy, normal growth, and absence of common transplant-related sequelae.

Results: Of 77 patients meeting inclusion criteria identified, 23 were long-term (≥10-year) survivors and were additionally assessed for ideal outcome attainment.

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

Background And Aims: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered.

Cost-Effectiveness of Primary Liver Transplantation Versus Hepatoportoenterostomy in the Management of Biliary Atresia in the United States.

Biliary atresia (BA) is the leading indication to perform a pediatric liver transplantation (LT). Timely hepatoportoenterostomy (HPE) attempts to interrupt the natural history and allow for enteric bile flow; however, most patients who are treated with HPE require LT by the age of 10 years. We determined the cost-effectiveness of foregoing HPE to perform primary LT (pLT) in children with BA compared with standard-of-care HPE management.

Pharmacological management of portal hypertension and its complications in children: lessons from adults and opportunities for the future.

Introduction: Portal hypertension (PHT) and its complications in children are thought to be distinct from adult PHT in several areas, including the underlying bio-physiology of a child in which PHT develops, but also because of the pediatric-specific etiologies that drive disease progression. And yet pharmacologic approaches to PHT in children are mainly based on adult data, modified for pediatric practice. This reality has been driven by a lack of data specific to children.

Living Related Liver Transplantation for Metabolic Liver Diseases in Children.

Metabolic liver diseases (MLDs) are a heterogeneous group of inherited conditions for which liver transplantation can provide definitive treatment. The limited availability of deceased donor organs means some who could benefit from transplant do not have this option. Living related liver transplant (LrLT) using relatives as donors has emerged as one solution to this problem.