HOPE Mitigates Ischemia-Reperfusion Injury in Ex-Situ Split Grafts: A Comparative Study With Living Donation in Pediatric Liver Transplantation.

Optimizing graft preservation is key for ex-situ split grafts in pediatric liver transplantation (PSLT). Hypothermic Oxygenated Perfusion (HOPE) improves ischemia-reperfusion injury (IRI) and post-operative outcomes in adult LT. This study compares the use of HOPE in ex-situ partial grafts to static cold storage ex-situ partial grafts (SCS-Split) and to the gold standard living donor liver transplantation (LDLT).

Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double-blind, randomised, placebo-controlled trial.

Background: In patients with Alagille syndrome, cholestasis-associated clinical features can include high serum bile acids and severe pruritus that can necessitate liver transplantation. We aimed to evaluate the efficacy and safety of the ileal bile acid transporter inhibitor odevixibat versus placebo in patients with Alagille syndrome.

Methods: The ASSERT study was a phase 3, double-blind, randomised, placebo-controlled trial that enrolled patients at 21 medical centres or hospitals in ten countries (Belgium, France, Germany, Italy, Malaysia, the Netherlands, Poland, Türkiye, the UK, and the USA).

∆-3-oxo-5β-reductase deficiency: favorable outcome in 16 patients treated with cholic acid.

Background: Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3β-hydroxy-Δ-C-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ-3-oxosteroid 5β-reductase (Δ-3-oxo-R) deficiency.

Determinants of early surgical complications after pediatric liver transplantation: A single center/single surgeon experience over 20 years.

Background: The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT.

Methods: All children receiving a first LT from October 1990 to October 2010 in our center were included.

Alpha1-antitrypsin deficiency: An updated review.

Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1 gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZ homozygous status and is favored by smoking.

Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) arises due to inherited variants in , the AAT gene that impairs the production or secretion of this hepatocellular protein and leads to a gain-of-function liver proteotoxicity. Homozygous Pi*Z pathogenic variant (Pi*ZZ genotype) is the leading cause of severe AATD. It manifests in 2 to 10% of carriers as neonatal cholestasis and 20 to 35% of adults as significant liver fibrosis.

Incidence of Isolated Biliary Atresia during the COVID Lockdown in Europe: Results from a Collaborative Project by RARE-Liver.

Background: Biliary atresia (BA) is a rare cholangiopathy where one of the proposed aetiological mechanisms is an infectious viral trigger. Coronavirus disease-19 (COVID) lockdown restrictions were implemented to reduce the transmission of infections. Strictness of lockdown varied across European countries.

Wilson Disease and Alpha1-Antitrypsin Deficiency: A Review of Non-Invasive Diagnostic Tests.

Wilson disease and alpha1-antitrypsin deficiency are two rare genetic diseases that may impact predominantly the liver and/or the brain, and the liver and/or the lung, respectively. The early diagnosis of these diseases is important in order to initiate a specific treatment, when available, ideally before irreversible organ damage, but also to initiate family screening. This review focuses on the non-invasive diagnostic tests available for clinicians in both diseases.

Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis.

Background: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool.

Hepatocyte proteomes reveal the role of protein disulfide isomerase 4 in alpha 1-antitrypsin deficiency.

Background & Aims: A single point mutation in the Z-variant of alpha 1-antitrypsin (Z-AAT) alone can lead to both a protein folding and trafficking defect, preventing its exit from the endoplasmic reticulum (ER), and the formation of aggregates that are retained as inclusions within the ER of hepatocytes. These defects result in a systemic AAT deficiency (AATD) that causes lung disease, whereas the ER-retained aggregates can induce severe liver injury in patients with ZZ-AATD. Unfortunately, therapeutic approaches are still limited and represents the option To overcome this limitation, a better understanding of the molecular basis of ER aggregate formation could provide new strategies for therapeutic intervention.

Combined use of creatinine and cystatin C improves the detection of renal dysfunction in children undergoing home parenteral nutrition.

Background: Renal dysfunction can complicate home parenteral nutrition (HPN). The aims were, in the context of pediatric HPN, to assess renal function using the measured glomerular filtration rate (mGFR), determine the most accurate formula(s) to estimate GFR, and identify possible underlying mechanisms of renal impairment.

Methods: A retrospective study was performed in 2 centers.

A Particular SORL1 Micro-haplotype May Prevent Severe Liver Disease in a French Cohort of Alpha 1-Antitrypsin-deficient Children.

The presence of modifier genes is now well recognized in severe liver disease outcome associated with alpha-1-antitrypsin deficiency (A1ATD) but their identification remains to be fully elucidated. To address this goal, we performed a candidate gene study with the SORL1 gene, already identified as risk gene in early-onset Alzheimer Disease families. A particular SORL1 micro-haplotype constituted with 3 SNPs (wild-type form TTG) was genotyped on 86 ZZ A1ATD children issued from 66 families.

Long term results of liver transplantation for alpha-1 antitrypsin deficiency.

Introduction: Liver transplantation (LT) is the therapeutic option for end-stage liver disease associated with alpha1 antitrypsin (A1AT) deficiency. The aim of the present retrospective study was to report on long-term outcomes following LT for A1AT deficiency.

Methods: The medical records of 90 pediatric and adult patients transplanted between 1982 and 2017 in France and Geneva (Switzerland) were reviewed.

Probiotic from human breast milk, Lactobacillus fermentum, promotes growth in animal model of chronic malnutrition.

Background: Chronic undernutrition leads to growth hormone resistance and poor growth in children, which has been shown to be modulated by microbiota. We studied whether Lactobacillus fermentum CECT5716 (Lf ), isolated from mother's breast milk, could promote juvenile growth through the modulation of lipid absorption in a model of starvation.

Methods: Germ-free (GF) Drosophila melanogaster larvae were inoculated with Lf in conditions of undernutrition with and without infant formula.

Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort.

Background & Aims: To identify prognostic factors for liver disease in children with alpha-1 antitrypsin deficiency, irrespective of phenotype, using the DEFI-ALPHA cohort.

Methods: Retrospective, then prospective from 2010, multicentre study including children known to have alpha-1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989.

SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children.

Background & Aims: Fifteen to twenty percent of alpha-1 antitrypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension - PHT) during childhood. Since they all share the same ZZSERPINA1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNPs located on the SERPINA1 and MAN1B1 genes have already been tested in very few studies with contradictory or not replicated results.

ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency.

Background: The most common and severe disease causing allele of Alpha 1-Antitrypsin Deficiency (1ATD) is Z-1AT. This protein aggregates in the endoplasmic reticulum, which is the main cause of liver disease in childhood. Based on recent evidences and on the frequency of liver disease occurrence in Z-1AT patients, it seems that liver disease progression is linked to still unknown genetic factors.