A5075460799- Pediatric Hepatobiliary Diseases and Treatments
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Neonatal Health and Biochemistry
- Liver Diseases and Immunity
- Gallbladder and Bile Duct Disorders
- Hepatitis B Virus Studies
- Amino Acid Enzymes and Metabolism
- Liver Disease and Transplantation
- Immunodeficiency and Autoimmune Disorders
- Congenital Anomalies and Fetal Surgery
- Pharmacological Effects and Toxicity Studies
- Folate and B Vitamins Research
- Diet and metabolism studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Intestinal Malrotation and Obstruction Disorders
- Congenital Diaphragmatic Hernia Studies
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Biomedical Research and Pathophysiology
- Acupuncture Treatment Research Studies
- Clinical Nutrition and Gastroenterology
- Diabetic Foot Ulcer Assessment and Management
- Chronic Lymphocytic Leukemia Research
Bicêtre Hospital
2012-2024
Université Paris-Saclay
2019-2024
Inserm
2019-2024
Assistance Publique – Hôpitaux de Paris
2011-2024
Université Paris-Sud
2013-2023
Laboratoire de Biochimie
2008-2022
Klinikum Rheine
2020
Universitätsklinikum Aachen
2013
BIO Intelligence Service (France)
2013
Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH) to initiate growth, protect cells, and sustain functions of the remnant liver. Bile acids (BAs), whose levels rise blood early PH, stimulate both hepatocyte proliferation protection, part through their binding nuclear farnesoid X receptor (FXR). However, effect BA receptor, TGR5 (G-protein-coupled 1) PH remains be studied. Liver histology, proliferation, concentrations (plasma, bile, liver, urine,...
Some patients with microvillus inclusion disease due to myosin 5B (MYO5B) mutations may develop cholestasis characterized by a progressive familial intrahepatic cholestasis-like phenotype normal serum gamma-glutamyl transferase activity. So far MYO5B deficiency has not been reported in such the absence of intestinal disease. Using new-generation sequencing approach, we identified five activity without Conclusion: These data show that lead isolated and should be considered as an additional...
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a result of mutations in ABCB11 encoding bile salt export pump (BSEP), the canalicular hepatocyte. In some PFIC2 patients with missense mutations, BSEP not detected at canaliculus owing to mistrafficking mutants. vitro, chaperone drugs, such as 4-phenylbutyrate (4-PB), have been shown partially correct mistrafficking. Four harboring least one mutation (p.G982R, p.R1128C, and p.T1210P) were treated orally 4-PB followed...
Progressive familial intrahepatic cholestasis type 3 is caused by biallelic variations of ABCB4, most often (≥70%) missense. In this study, we examined the effects 12 missense identified in progressive patients. We classified these on basis defects thus and explored potential rescue trafficking‐defective mutants pharmacological means. Variations were reproduced ABCB4 complementary DNA mutants, obtained, expressed HepG2 HEK293 cells. Three either fully (I541F L556R) or largely (Q855L)...
The present report describes CFC1 gene analysis in 10 patients with polysplenia syndrome. heterozygous transition c.433G>A (Ala145Thr) located exon 5 was identified patients, a twice-higher frequency than control patients. These results suggest that mutation may represent genetic predisposition to biliary atresia splenic malformation
Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn-SOD Mn-SOD), glutathione peroxidase (GPx), catalase) non-enzymatic antioxidant systems. We aimed to determine, in patients with non-alcoholic fatty liver disease (NAFLD), the level of defenses (1) biopsies, demonstrate existence stress; (2) erythrocytes plasma, determine whether their reflect stress.Erythrocyte plasma were prospectively studied two...
Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis its natural history, effects predicted protein truncating mutations (PPTMs), and possible associations serum bile acid (sBA) concentrations surgical biliary diversion (SBD) with long-term outcome. We aimed provide insights by using the largest genetically defined cohort...
The canalicular bile salt export pump (BSEP/ABCB11) of hepatocytes is the main adenosine triphosphate (ATP)-binding cassette (ABC) transporter responsible for acid secretion. Mutations in ABCB11 cause several cholestatic diseases, including progressive familial intrahepatic cholestasis type 2 (PFIC2) often lethal absence liver transplantation. We investigated vitro effect and potential rescue a BSEP mutation by ivacaftor, clinically approved cystic fibrosis transmembrane conductance...
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disease caused by biallelic variations in ABCB4. Data reporting on the impact of genotype and response to ursodeoxycholic acid (UDCA) therapy long-term outcomes are scarce.We retrospectively describe cohort 38 patients with PFIC3 median age at last follow-up 19.5 years (range 3.8-53.8).Twenty presented symptoms before 1 year age. Thirty-one received resulting serum test improvement 20. Twenty-seven had cirrhosis 8.1...
A 19 year old woman with tyrosinaemia type 1 gave birth to a healthy girl after 41 weeks of gestation. Nitisinone was continued throughout the pregnancy (maternal levels 68–96 μmol/l, target level 30–60 μmol/l). Tyrosine during were between 500 and 693 μmol/l (normal values 20–120 μmol/l) phenylalanine 8 39 30–100 measurable in neonatal blood immediately birth, at comparable simultaneous mother. half-life neonate estimated be 90 h. decreased from 1,157 (cord blood) normal within 4 weeks....
Transient neonatal cholestasis (TNC) is a form of spontaneously resolving that results from the association several factors, including immaturity bile secretion and perinatal disease leading to hepatic ischemia or hypoxia (1). Although it obvious this preferentially appears in children who experienced distress, 10% with TNC no remarkable event identified (1–3). In contrast, some do not develop (3). These findings suggest genetic predisposition may be involved trigger mechanism TNC. This...
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. The objective this study evaluate the use NGS in children with cholestasis.Children presenting cholestasis were included between 2015 2020. was performed targeted capture panel 34 genes involved jaundice. Patients classified into...
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is a severe hepatocellular due to biallelic mutations in ABCB11 encoding the canalicular bile salt export pump (BSEP). Nonsense are responsible for most phenotypes. The aim was assess ability of drugs induce readthrough six nonsense (p.Y354X, p.R415X, p.R470X, p.R1057X, p.R1090X, and p.E1302X) identified patients with PFIC2.The G418, gentamicin, PTC124 studied using dual gene reporter system NIH3T3 cells. gentamicin lead expression...
Hereditary tyrosinemia type 1 (HT1) is a rare autosomal recessive disorder of phenylalanine and tyrosine catabolism due to deficiency fumarylacetoacetate hydrolase. HT1 has large clinical spectrum with acute forms presenting before six months age, subacute initial symptoms occurring between age 6 12 months, chronic after age. Without treatment, results in the accumulation toxic metabolites leading liver disease, proximal tubular dysfunction, porphyria-like neurological crises. Since early...
Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in