Publications by authors named "Florence Lacaille"

107 Publications

Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis.

Eur Respir J 2021 Sep 9. Epub 2021 Sep 9.

AP-HP, Service de Pneumologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Centre de Référence pour les Maladies Respiratoires Rares de l'Enfant, Paris, France.

Introduction: Pulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase () gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease.

Methods: Four patients received methionine supplementation and were followed for respiratory, hepatic, growth, and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species (ROS) production by patient monocytes before and after methionine supplementation was also studied.

Results: Methionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material, and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or non-invasive ventilation could be weaned off within 60 days. Liver dysfunction, inflammation, and growth delay also improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes.

Conclusion: Methionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in the gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.01554-2021DOI Listing
September 2021

Therapeutic plasma exchange for life-threatening pediatric disorders.

J Clin Apher 2021 Sep 1. Epub 2021 Sep 1.

Hôpital Necker Enfants Malades, Paris, France.

Introduction: Therapeutic plasma exchange (TPE) is acknowledged to be an effective treatment in life-threatening pediatric disorders. Apheresis for pediatric diseases has been poorly investigated, and most studies to date featured small numbers of patients and lacked control groups. The objective of the present study was to evaluate the tolerance of TPE in pediatric patients.

Materials And Methods: A retrospective cohort study via a web-based electronic case report form including pediatric patients referred for TPE between January 2005 and December 2014.

Results: A total of 78 patients (median [range] age: 9.8 [0.53-17.93]) and 731 TPE procedures were analyzed. The indications were antibody-mediated rejection (n = 33; 42%) and desensitization therapy (n = 5; 6%) after solid organ or hematopoietic stem cell transplantation, thrombotic microangiopathy (n = 17; 22%), pediatric inflammatory diseases (n = 16; 21%), kidney diseases (n = 6; 8%), and hyperviscosity syndrome (n = 1; 1%). On average, each patient underwent six procedures during the first session [range: 1-19]. In the 2 weeks following the start of a session, 72 patients (92%) presented a total of 311 adverse events (AEs) potentially related to TPE. The risk of AEs was not related to the indication for TPE, the intensity of care, venous access, plasma substitute use, or body weight. None of the deaths was related to the TPE.

Conclusion: We studied one of the largest retrospective pediatric cohorts described to date. Our experience of TPE children's TPE feasibility concerned specific, life-threatening conditions and otherwise treatment-refractory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jca.21934DOI Listing
September 2021

Effects of odevixibat on pruritus and bile acids in children with cholestatic liver disease: Phase 2 study.

Clin Res Hepatol Gastroenterol 2021 Jun 26;45(5):101751. Epub 2021 Jun 26.

Albireo Pharma, Boston, MA, United States.

Purpose: Ileal bile acid transporter inhibition is a novel therapeutic concept for cholestatic pruritus and cholestatic liver disease progression. Odevixibat, a potent, selective, reversible ileal bile acid transporter inhibitor, decreases enteric bile acid reuptake with minimal systemic exposure. Oral odevixibat safety, tolerability, and efficacy in pediatric patients with cholestatic liver disease and pruritus were evaluated.

Patients And Methods: In this phase 2, open-label, multicenter study, children received 10‒200 μg/kg oral odevixibat daily for 4 weeks. Changes in serum bile acid levels (primary efficacy endpoint), pruritus, and sleep disturbance were explored.

Results: Twenty patients were enrolled (8 females; 1‒17 years; 4 re-entered at a different dose). Diagnoses included progressive familial intrahepatic cholestasis (n = 13; 3 re-entries), Alagille syndrome (n = 6), biliary atresia (n = 3), and other intrahepatic cholestasis causes (n = 2; 1 re-entry). Mean baseline serum bile acid levels were high (235 µmol/L; range, 26‒564) and were reduced in the majority (-123.1 μmol/L; range, -394 to 14.5, reflecting reductions of up to 98%). Patient-reported diary data documented improved pruritus (3 scales) and sleep. With 100 μg/kg, mean (SEM) decrease was 2.8 (1.1) points for pruritus (visual analogue itch scale 0-10) and 2.9 (0.9) points for sleep disturbance (Patient-Oriented Scoring Atopic Dermatitis scale 0-10). Reduced pruritus correlated significantly with reduced serum bile acids (P ≤ 0.007). Significant correlations were also observed between autotaxin levels and pruritus. All patients completed the study. No serious adverse events were treatment related; most adverse events, including increased transaminases, were transient.

Conclusions: Orally administered odevixibat was well tolerated, reduced serum bile acids, and improved pruritus and sleep disturbance in children with cholestatic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2021.101751DOI Listing
June 2021

Biliary and duodenal complications after « en bloc» liver-small bowel transplantation in children. A single center cohort study.

Pediatr Transplant 2021 Sep 13;25(6):e14014. Epub 2021 Jun 13.

Pediatric Surgery, Hôpital Universitaire Necker-Enfants Malades, APHP, Paris, France.

Background: The technique of « en bloc» liver and small bowel transplantation (L-BT) spares a biliary anastomosis, but does not protect against biliary complications. We analyze biliary and duodenal complications (BDC) in our pediatric series.

Methods: Between 1994 and 2020, 54 L-BT were performed in 53 children. The procurement technique included in situ vascular dissection and pancreatic reduction to the head until 2009 (group A). Thereafter, the whole pancreas was recovered (group B).

Results: Nine BDCs occurred in 8/53 (15%) patients (7 in group A and 1 in group B): leak of the donor's duodenal stump (2), stenosis of the extra-pancreatic bile duct (5), and intra-pancreatic bile duct stenosis (2). Median delay for diagnosis of stricture was 8 months (4-168). Interventional radiology was successful in one child only, the others required reoperations. Two patients died, of biliary cirrhosis or cholangitis, 15-month and 12-year post-L-BT. One was listed and liver re-transplanted 13 years post-L-BT. At last follow-up, two patients only had normal liver tests and ultrasound.

Conclusion: BDC after L-BT can cause severe morbidities. Pancreatic reduction might increase this risk. Early surgical complications or chronic pancreatic rejection might be co-factors. Early diagnosis and treatment are key to the long-term prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.14014DOI Listing
September 2021

Peritoneovenous Shunt for Intractable Ascites in Children: A Series of 4 Cases.

J Pediatr Gastroenterol Nutr 2021 07;73(1):e7-e10

Pediatric Surgery Unit.

Abstract: Intractable ascites is a rare condition in children mainly caused by cirrhosis or lymphatic disorders. Internal drainage may be considered as rescue therapy. In our department, 4 patients ages from 2 months to 15 years old underwent a peritoneovenous shunt (PVS) placement between 2010 and 2020. The surgically inserted device was a pumping device that enabled to drain ascites from the peritoneum into the venous system via the internal jugular vein (Denver shunt, BD Company, NJ). Immediate efficient drainage was achieved in all cases and lasted up to 9 years. Two major complications occurred: a postoperative fat embolism requiring urgent temporary ligation of the shunt and endocarditis shortly after inguinal hernia repair performed 16 months after placement of the shunt. Implementation of a PVS may be a useful procedure in patients with refractory ascites. Chylous ascites should be drained and washed totally before activating the device to avoid fat embolism. Antibiotic prophylaxis is required when abdominal surgery is planned while the device is in place.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003131DOI Listing
July 2021

Large-scale screening of lipase acid deficiency in at risk population.

Clin Chim Acta 2021 Aug 20;519:64-69. Epub 2021 Apr 20.

Department of Hepatology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique Hopitaux de Paris, Paris, France; University Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale UMR 938, Paris, France.

Background: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD).

Methods: This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots.

Results: LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel.

Conclusion: This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2021.04.005DOI Listing
August 2021

Lipids Responsible for Intestinal or Hepatic Disorder: When to Suspect a Familial Intestinal Hypocholesterolemia?

J Pediatr Gastroenterol Nutr 2021 07;73(1):4-8

Univ. Lyon, Hospices Civil de Lyon, Gastro-enterology and Pediatric Nutrition, Reference Center for Intestinal Rare Disease (MaRDi), Hôpital Femme Mere Enfant, Bron.

Abstract: Familial intestinal hypocholesterolemias, such as abetalipoproteinemia, hypobetalipoproteinemia, and chylomicron retention disease, are rare genetic diseases that result in a defect in the synthesis or secretion of lipoproteins containing apolipoprotein B.In children, these conditions present with diarrhoea and growth failure, whereas adults present with neuromuscular, ophthalmological, and hepatic symptoms. Simple laboratory investigations have shown that diagnosis can be made from findings of dramatically decreased cholesterol levels, deficiencies in fat-soluble vitamins (mostly vitamin E), endoscopic findings of the characteristic white intestinal mucosa, and fat-loaded enterocytes in biopsy samples. Genetic analysis is used to confirm the diagnosis. Treatment is based on a low-fat diet with essential fatty acid supplementation, high doses of fat-soluble vitamins, and regular and life-long follow-up.The present study examines cases and literature findings of these conditions, and emphasises the need to explore severe hypocholesterolemia and deficiencies in fat-soluble vitamins to not miss these rare, but easy to diagnose and treat, disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003145DOI Listing
July 2021

Long-Term Results of Laparoscopic Adjustable Gastric Banding in French adolescents: The Utmost Importance of Follow-Up.

J Pediatr Gastroenterol Nutr 2021 06;72(6):906-911

Hôpital Universitaire Necker - Enfants Malades, Department of Pediatric Gastroenterology-Hepatology-Nutrition.

Objectives: To investigate the long-term follow-up (FU) and effectivity of laparoscopic adjustable gastric banding (LAGB) in a French adolescent cohort.

Methods: We retrospectively analyzed the results of LAGB at our institution. We collected information on FU, adjustable gastric banding (AGB) status, weight-related parameters, and comorbidity at multiple timepoints.

Results: Fifty-six patients (77% female) with a mean age of 16.5 years and a mean body mass index (BMI) of 45 kg/m2 underwent LAGB over a period of 12 years. The mean postpediatric FU was 23 months. FU decreased progressively from 96% at 3 years to 54% and 29% at 6 and 9 years, respectively. The loss to FU was 39% at last contact. AGB was removed in 17 patients (30%) and 12 patients (21%) underwent a second bariatric procedure. Mean BMI decreased by 11 kg/m2 at last contact (P < 0.001). The prevalence of most comorbidities also decreased significantly after 3 years. The mean excess weight loss (to reach a BMI of 25 kg/m2) was 47% during the first year postsurgery and further increased to 55% at last contact.

Conclusion: Overall, AGB resulted in significant weight loss; however, the increase in heterogeneity suggests that LAGB is more effective in some individuals than in others in the long-term. This study confirmed that LAGB is a valuable bariatric procedure in adolescents, either as a long term-term efficient or bridging method that would be replaced at the time of transition to adult care. The importance of a standardized long-term follow-up should always be emphasized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003092DOI Listing
June 2021

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

Hepatology 2021 Aug 13;74(2):892-906. Epub 2021 Jul 13.

European Reference Network on Hepatological Diseases.

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.

Approach And Results: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 μmol/L (P = 0.05) tended to be associated with improved NLS.

Conclusions: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456904PMC
August 2021

Quality of life in long term survivors of pediatric intestinal transplantation compared with liver transplantation and home parenteral nutrition: A prospective single-center pilot study.

Pediatr Transplant 2021 May 16;25(3):e13982. Epub 2021 Feb 16.

Gastroenterology-Hepatology-Nutrition Unit, Hôpital Necker-Enfants Malades, Paris, France.

Health-related quality of life (HRQOL) after intestinal transplantation (IT) is important, as many psychological troubles have been reported in these patients on the long term. Our aim was to assess and compare HRQOL of patients after IT to patients after liver transplantation (LT) or on home parenteral nutrition (HPN) for intestinal failure. A cross-sectional study included patients and their parents between 10 and 18 years of age, on HPN for more than 2 years, or who underwent IT or LT, with a graft survival longer than 2 years. Quality of life was explored by Child Health Questionnaire. Thirteen children-parents dyads after IT, 10 after LT, and eight children on HPN completed the survey. Patients were a median age of 14 years old, a median of 10 years post-transplantation or on HPN. Patients after IT scored lower than patients after LT or on HPN in "social limitations due to behavioral difficulties" and in "behavior." They scored higher than those on HPN in "global health." Parents of children after IT scored lower than those after LT in many domains. No relevant correlation with clinical data was found. Our study showed the multi-level impact of IT on quality of life of patients and their parents. It highlights the importance of a regular psychological follow-up for patients, but also of a psychological support for families. Helping the patients to overcome the difficulties at adolescence may improve their mental health in adulthood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13982DOI Listing
May 2021

Arterial abnormalities identified in kidneys transplanted into children during the COVID-19 pandemic.

Am J Transplant 2021 05 18;21(5):1937-1943. Epub 2021 Feb 18.

INSERM U1163, Institut Imagine, Paris, France.

Graft artery stenosis can have a significant short- and long-term negative impact on renal graft function. From the beginning of the COVID-19 pandemic, we noticed an unusual number of graft arterial anomalies following kidney transplant (KTx) in children. Nine children received a KTx at our center between February and July 2020, eight boys and one girl, of median age of 10 years. Seven presented Doppler features suggesting arterial stenosis, with an unusual extensive pattern. For comparison, over the previous 5-year period, persistent spectral Doppler arterial anomalies (focal anastomotic stenoses) following KTx were seen in 5% of children at our center. We retrospectively evidenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in five of seven children with arterial stenosis. The remaining two patients had received a graft from a deceased adolescent donor with a positive serology at D0. These data led us to suspect immune postviral graft vasculitis, triggered by SARS-CoV-2. Because the diagnosis of COVID-19 is challenging in children, we recommend pretransplant monitoring of graft recipients and their parents by monthly RT-PCR and serology. We suggest balancing the risk of postviral graft vasculitis against the risk of prolonged dialysis when considering transplantation in a child during the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16464DOI Listing
May 2021

Clinical management of sickle cell liver disease in children and young adults.

Arch Dis Child 2021 04 11;106(4):315-320. Epub 2020 Nov 11.

Paediatric Liver, GI and Nutrition Centre and MowatLabs, King's College Hospital NHS Foundation Trust, London, UK

Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2020-319778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610372PMC
April 2021

Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease.

Pediatr Nephrol 2021 05 9;36(5):1165-1173. Epub 2020 Nov 9.

Department of Gastroenterology-Hepatology-Nutrition, Reference Center for Biliary Atresia and Cholestatic Genetic Diseases, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Paris, France.

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood.

Methods: Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study.

Results: Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt.

Conclusions: Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04808-9DOI Listing
May 2021

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

Dig Liver Dis 2021 May 1;53(5):606-611. Epub 2020 Nov 1.

Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des spécialités digestives, Lyon, France; Université de Lyon, Lyon, France. Electronic address:

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.

Results: The study population consisted of 32 adults and 58 children; median age at transplant was 13.0 years (range: 0.2-65.1), and 65 were male (72.2%). Eighty-two patients (94.8% of children and 84.4% of adults) had the PI*ZZ genotype/phenotype and eight patients (8.9%) had the Pi*SZ genotype/phenotype. Eighty-four patients (93.3%) were transplanted for end-stage liver disease and six (all Pi*ZZ adults) for HCC. Median follow-up after LT was 13.6 years (0.1-31.7). The overall cumulative patient survival rates post-transplant were 97.8% at 1 year, and 95.5%, 95.5%, 92.0%, 89.1% at 5, 10, 15, 20 years respectively. The overall cumulative graft survival rates were 92.2% at 1 year, and 89.9%, 89.9%, 84.4%, 81.5% at 5, 10, 15 and 20 years, respectively.

Conclusions: In a representative cohort of patients having presented with end-stage-liver disease or HCC secondary to A1AT, liver transplantation offered very good patient and graft survival rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.10.016DOI Listing
May 2021

Long term outcome of MPI-CDG patients on D-mannose therapy.

J Inherit Metab Dis 2020 11 9;43(6):1360-1369. Epub 2020 Aug 9.

Inserm U1151, Institut Necker Enfants-Malades, Paris, France.

Mannose phosphate isomerase MPI-CDG (formerly CDG-1b) is a potentially fatal inherited metabolic disease which is readily treatable with oral D-mannose. We retrospectively reviewed long-term outcomes of patients with MPI-CDG, all but one of whom were treated with D-mannose. Clinical, biological, and histological data were reviewed at diagnosis and on D-mannose treatment. Nine patients were diagnosed with MPI-CDG at a median age of 3 months. The presenting symptoms were diarrhea (n = 9), hepatomegaly (n = 9), hypoglycemia (n = 8), and protein loosing enteropathy (n = 7). All patients survived except the untreated one who died at 2 years of age. Oral D-mannose was started in eight patients at a median age of 7 months (mean 38 months), with a median follow-up on treatment of 14 years 9 months (1.5-20 years). On treatment, two patients developed severe portal hypertension, two developed venous thrombosis, and 1 displayed altered kidney function. Poor compliance with D-mannose was correlated with recurrence of diarrhea, thrombosis, and abnormal biological parameters including coagulation factors and transferrin profiles. Liver fibrosis persisted despite treatment, but two patients showed improved liver architecture during follow-up. This study highlights (i) the efficacy and safety of D-mannose treatment with a median follow-up on treatment of almost 15 years (ii) the need for life-long treatment (iii) the risk of relapse with poor compliance, (iii) the importance of portal hypertension screening (iv) the need to be aware of venous and renal complications in adulthood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12289DOI Listing
November 2020

Long-term results of pediatric liver transplantation for autoimmune liver disease.

Clin Res Hepatol Gastroenterol 2021 May 17;45(3):101537. Epub 2020 Oct 17.

Université Claude Bernard Lyon 1, Lyon, France; Hospices Civils de Lyon, Hôpital Edouard Herriot, Femme-Mère-Enfant, Service d'Hépato-gastroentérologie, Lyon, France. Electronic address:

Background: Autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are rare indications for liver transplantation (LT) in children. The aim of the present retrospective multicenter study was to evaluate long-term outcome after LT for autoimmune liver disease in childhood.

Methods: Retrospective data from 30 children who underwent a first LT from 1988 to 2018 were collected.

Results: The study population consisted of 18 girls and 12 boys, transplanted for AIH type 1 (n=14), AIH type 2 (n=7) or PSC (n=9). Mean age at LT was 11.8±5.2 years. The main indications for LT were acute (36.7%) or chronic end-stage liver failure (63.3%). Graft rejection occurred in 19 patients (63.3%); 6 pts required retransplantation for chronic rejection. Recurrence of initial disease was observed in 6 patients (20.0%), all of them with type 1 AIH, after a median time of 42 months, requiring retransplantation in 2 cases. Overall patient survival rates were 96.4%, 84.6%, 74.8%, 68.0%, 68.0%, 68.0% and 68.0% at 1, 5, 10, 15, 20, 25 and 30 years, respectively. Age at LT<1year (p<0.0001), LT for fulminant failure (p=0.023) and LT for type 2 AIH (p=0.049) were significant predictive factors of death.

Conclusion: Long-term outcome after LT for pediatric autoimmune liver disease is impaired in patients with AIH because of consistent complications such as rejection and disease recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.08.013DOI Listing
May 2021

The Liver in Sickle Cell Disease.

J Pediatr Gastroenterol Nutr 2021 01;72(1):5-10

Department of Pediatric Gastroenterology-Hepatology-Nutrition, Reference Centre for Biliary Atresia and Genetic Cholestasis and Department of General Pediatrics and Pediatric Infectious Diseases, Reference Centre for Sickle Cell Disease; Hôpital Universitaire Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.

Abstract: Liver involvement is found in nearly 40% of children with sickle cell disease. The most frequent complication is cholelithiasis. The most severe complication is acute hepatic crisis, with symptoms ranging from increasing jaundice to multiple organ failure and death. The emergency and mostly efficient treatment is exchange transfusion. Chronic cholangiopathy is increasingly recognized, with autoimmune features in most cases, worsened by chronic ischemia. Transfusion-related iron overload is not yet a concern in children, and hepatotoxicity of iron chelators is rare. We propose recommendations to prevent, explore, and treat these complications. We emphasize the close collaboration required between hepatologists and specialists of sickle cell disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002886DOI Listing
January 2021

Novel CLDN1 Deletion Associated with Ichthyosis, Sclerosing Cholangitis and Acquired Alopecia.

Acta Derm Venereol 2020 Jun 11;100(13):adv00173. Epub 2020 Jun 11.

Department of Dermatology, Necker Hospital, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2340/00015555-3522DOI Listing
June 2020

Beyond 10 years, with or without an intestinal graft: Present and future?

Am J Transplant 2020 10 3;20(10):2802-2812. Epub 2020 May 3.

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Necker-Enfants Malades Hospital, University of Paris, Paris, France.

Long-term outcomes in children undergoing intestinal transplantation remain unclear. Seventy-one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10-year posttransplant outcomes with (group 1, n = 26) and without (group 2, n = 9) a functional graft. Ten-year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87 mL/min/1.73 m . Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10 years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3-drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15899DOI Listing
October 2020

Early Bacterial Infections After Pediatric Liver Transplantation in the Era of Multidrug-resistant Bacteria: Nine-year Single-center Retrospective Experience.

Pediatr Infect Dis J 2020 08;39(8):e169-e175

From the Service de réanimation et surveillance continue médico-chirurgicales pédiatriques, Hôpital Necker Enfants Malades, AP-HP, Université de Paris, Paris, France.

Background: Early bacterial infection is a major and severe complication after liver transplantation (LT). The rise of antimicrobial resistance, especially extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), is a growing concern for these patients. This study aimed to assess the epidemiology of early bacterial infections in a pediatric population, including those caused by multidrug-resistant (MDR) pathogens, and to identify risk factors for infection.

Methods: We conducted a monocentric retrospective study including 142 consecutive LTs performed in 137 children between 2009 and 2017.

Results: Ninety-three bacterial infections occurred after 67 (47%) LTs. Among the 82 isolated pathogens, the most common was Klebsiella pneumoniae (n = 19, 23%). Independent risk factors for early bacterial infection were low weight [odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.9-0.99; P = 0.03] and the presence of a prosthetic mesh (OR = 2.4; 95% CI: 1.1-5.4; P = 0.046). Sixty-one children (45%) carried MDR bacteria and 16 infections were caused by MDR pathogens, especially ESBL-producing K. pneumoniae (n = 12). ESBL-PE stool carriage was associated with ESBL-PE infection (OR = 4.5; 95% CI: 1.4-17.4; P = 0.02). Four children died from an infection, three due to ESBL-producing K. pneumoniae.

Conclusions: This study confirmed a shift toward a predominance of Gram-negative early bacterial infections after pediatric LT. The risk factors for infection were low weight and the presence of a prosthetic mesh. ESBL-PE stool carriage was associated with ESBL-PE infection. Adapted antimicrobial prophylaxis and personalized antibiotherapy are mandatory to reduce infection prevalence and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000002662DOI Listing
August 2020

Genotype correlates with the natural history of severe bile salt export pump deficiency.

J Hepatol 2020 07 20;73(1):84-93. Epub 2020 Feb 20.

European Reference Network on Hepatological Diseases (ERN RARE-LIVER); Pediatric Liver Service, La Paz University Hospital, Madrid, Spain.

Background & Aims: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date.

Methods: This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category.

Results: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 μmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001).

Conclusions: The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS.

Lay Summary: This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.02.007DOI Listing
July 2020

Administration of gamma-hydroxybutyrate instead of beta-hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error.

JIMD Rep 2020 Jan 3;51(1):25-29. Epub 2020 Jan 3.

Reference Center for Inherited Metabolic Diseases Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris Paris France.

Beta-hydroxybutyrate (BHB) is a synthetic ketone body used as an adjuvant energy substrate in the treatment of patients with metabolic cardiomyopathy. A medication prescribing error led to the administration of the general anesthetic sodium gamma-hydroxybutyrate (GHB) instead of sodium BHB in a liver transplant recipient with propionic acidemia and cardiomyopathy, causing acute coma. A 15-year-old boy suffering from neonatal propionic acidemia underwent liver transplantation (LT) for metabolic decompensation and cardiomyopathy (treated with cardiotropic drugs and BHB) diagnosed a year previously. The patient had been rapidly extubated after LT, and was recovering well. Eight days after LT, the patient suddenly became comatose. No metabolic, immunological, hypertensive, or infectious complications were apparent. The brain magnetic resonance imaging and electroencephalography results were normal. The coma was soon attributed to a medication prescribing error: administration of GHB instead of BHB on day 8 post-LT. The patient recovered fully within a few hours of GHB withdrawal. The computerized prescription system had automatically suggested the referenced anesthetic GHB (administered intravenously) instead of the non-referenced ketone body BHB, triggering coma in our patient. A computerized prescription system generated a medication prescribing error for a rare disease, in which the general anesthetic GHB was mistaken for the nonreferenced energy substrate BHB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmd2.12090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012734PMC
January 2020

Donor-targeted serotherapy as a rescue therapy for steroid-resistant acute GVHD after HLA-mismatched kidney transplantation.

Am J Transplant 2020 08 10;20(8):2243-2253. Epub 2020 Mar 10.

Etablissement Français du Sang, St. Denis, France.

Acute graft-versus-host disease (GVHD) is a rare but frequently lethal complication after solid organ transplantation. GVHD occurs in unduly immunocompromised hosts but requires the escalation of immunosuppression, which does not discriminate between host and donor cells. In contrast, donor-targeted therapy would ideally mitigate graft-versus-host reactivity while sparing recipient immune functions. We report two children with end-stage renal disease and severe primary immune deficiency (Schimke syndrome) who developed severe steroid-resistant acute GVHD along with full and sustained donor T cell chimerism after isolated kidney transplantation. Facing a therapeutic dead end, we used a novel strategy based on the adoptive transfer of anti-HLA donor-specific antibodies (DSAs) through the transfusion of highly selected plasma. After approval by the appropriate regulatory authority, an urgent nationwide search was launched among more than 3800 registered blood donors with known anti-HLA sensitization. Adoptively transferred DSAs bound to and selectively depleted circulating donor T cells. The administration of DSA-rich plasma was well tolerated and notably did not induce antibody-mediated rejection of the renal allografts. Acute GVHD symptoms promptly resolved in one child. This report provides a proof of concept for a highly targeted novel therapeutic approach for solid organ transplantation-associated GVHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15827DOI Listing
August 2020

Hepatobiliary Complications in Children with Sickle Cell Disease: A Retrospective Review of Medical Records from 616 Patients.

J Clin Med 2019 Sep 18;8(9). Epub 2019 Sep 18.

Department of Pediatric Gastroenterology-Hepatology-Nutrition, Hepatology Unit, Necker-Enfants malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris, 75005 Paris, France.

Hepatobiliary complications in children with sickle cell disease (SCD) are rarely reported but can be life-threatening. We retrospectively assessed their prevalence in a cohort of 616 children followed in a French university-hospital SCD reference center. Eligibility criteria were the following: age <18 years, seen at least twice with an interval of more than 6 months from January 2008 to December 2017, with all genotypes of SCD. Patients with hepatobiliary complications were identified via the local data warehouse and medical files were thoroughly reviewed. At least one hepatobiliary complication was reported in 37% of the children. The most frequent was cholelithiasis, in 25% of cases, which led to systematic screening and elective cholecystectomy in the case of gallstones. Overall, 6% of the children experienced acute sickle cell hepatic crisis, sickle cell intra-hepatic cholestasis, or acute hepatic sequestration, with severity ranging from mild liver pain and increased jaundice to multiple organ failure and death. Emergency treatment was exchange transfusion, which led to normalization of liver tests in most cases. Five children had chronic cholangiopathy, associated with auto-immune hepatitis in two cases. One needed liver transplantation, having a good outcome but with many complications. Transfusion iron load and infectious hepatitis cases were mild. Hepatotoxicity of an iron chelator was suspected to contribute to abnormal liver test results in five patients. We propose recommendations to prevent, explore, and treat hepatobiliary complications in SCD children. We underline the need for emergency exchange transfusion when acute liver failure develops and warn against liver biopsy and transplantation in this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8091481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780325PMC
September 2019

Pediatric intestinal transplantation: Analysis of the intestinal transplant registry.

Pediatr Transplant 2019 12 18;23(8):e13580. Epub 2019 Sep 18.

Department of Surgery, Hillman Center for Pediatric Transplantation, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.

The ITR serves as an international database for centers around the world to contribute to current knowledge about intestinal transplant outcomes. Led by the IRTA and managed by the Terasaki Research Institute, the ITR collects data annually and uses these data to generate reports that guide management strategies and policy statements. The aim of this manuscript was to analyze outcomes specific to pediatric intestinal transplantation. Outcome data for children transplanted from 1985 to 2017 were analyzed and predictive factors assessed. A total of 2010 children received 2080 intestine containing allografts during this period. Overall, 1-year and 5-year patient and graft survival were 72.7%/66.1% and 57.2/48.8%, respectively. One-year conditional survival was most strongly associated with being a first-time transplant recipient and liver-inclusive grafts. Patient survival was most strongly associated with elective status of transplantation as compared with hospitalized status. Enteral autonomy following transplantation has continued to improve by era with colonic inclusion demonstrating additional incremental improvement in enteral autonomy and freedom from intravenous fluid. While PTLD and technical complications contribute less to graft loss than in earlier eras, rejection remains the largest contributor to long-term graft loss. Re-transplantation is linked with significantly worse conditional graft survival, and sepsis remains the largest contributor to patient death. Newer data elements are focusing on impact of donor variables, donor and recipient tissue typing, and impact of the development of de novo antibodies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/petr.13580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879795PMC
December 2019

Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.

J Inherit Metab Dis 2020 03 11;43(2):234-243. Epub 2020 Feb 11.

Reference Center of Pediatric Nephrology, Hôpital Universitaire Necker-Enfants Malades, APHP, Filière ORKID, ERKnet, University Paris Descartes, Paris, France.

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12174DOI Listing
March 2020

Seroprevalence of Hepatitis E virus infection in children after liver transplantation: A single-center experience in France.

Clin Res Hepatol Gastroenterol 2020 04 29;44(2):174-180. Epub 2019 Jun 29.

Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, AP-HP, 149, Sèvres Street, 75015 Paris, France; University of Paris-Descartes, Sorbonne Paris-Cité, 75006 Paris, France.

Introduction: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide, usually asymptomatic in children. However, a growing number of publications over the last decade have documented cases of chronic hepatitis related to HEV-genotype 3 infection, and progressing to cirrhosis in immuno-compromised patients, particularly in adult kidney transplant recipients. The aim of our study was to evaluate the prevalence and severity of HEV infection among pediatric liver transplant (PLT) recipients managed in our center.

Material And Methods: Between November 1 2014 and January 1 2016, PLT recipients (less than 18 years-old) were screened for HEV infection [determined by HEV serology, HEV- immunoglobulin M (IgM) and immunoglobulin G (IgG), and HEV-ribonucleic acid (RNA) by reverse transcriptase polymerase chain reaction] at their annual follow-up visit.

Results: Eighty children were tested for HEV infection a mean of 5.4±5.3 years after liver transplantation (LT). The main indication for LT was biliary atresia (n=47, 59%). The prevalence of HEV-IgG was 8% (n=6; age range 1.3 to 14.2 years-old at the time of HEV testing). Prevalence increased to 30% when considering only the 20 children with a past history of an unexplained episode of elevated transaminases since LT. None had HEV IgM, serum HEV-RNA, or increased transaminases at the time of HEV testing. Among the six IgG seropositive children, two had received intravenous immunoglobulins prior to screening and four children had a negative control (seroreversion) 3 to 42 months after the first testing.

Conclusion: The prevalence of HEV infection in our cohort is low and similar to other pediatric reports. We saw no cases of chronic hepatitis or fibrosis attributable to HEV. The lower immunosuppressive regimen used in PLT children compared to other solid organ transplant recipients may account for this good outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2019.06.002DOI Listing
April 2020

Clostridium difficile: A Frequent Infection in Children After Intestinal Transplantation.

Transplantation 2020 01;104(1):197-200

Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Université Paris Descartes - Sorbonne Paris Cité, Paris, France.

Background: Organ transplantation (Tx) is a risk factor for Clostridium difficile infection (CDI). After intestinal transplantation (ITx), few data are available on the impact of this graft infection and the possible induction of rejection.

Methods: We included retrospectively all children after ITx in our unit, with at least 1 year of graft survival. All samples positive for Clostridium difficile (CD) and its toxin were considered.

Results: Among the 57 ITx recipients (60 Txs), 22 children (39%) developed culture-proven CDI, 12 after isolated small bowel Tx, 9 after liver-small bowel Tx, and 1 after multivisceral Tx. Twenty patients had diarrhea, 8 bloody stools, 4 fever, and 1 hypothermia. Nine were hospitalized for an average of 6.5 days (2-20) and 4 with severe dehydration. Nine (40%) had received antibiotics for an average of 19 days (7-60) before CDI. Two patients were asymptomatic. CDI was treated with metronidazole in 12 children, vancomycin in 6, and both in 3. Three children presented mild-to-severe rejections. Two patients presented concomitantly CDI and rejection. The third patient presented a rejection with severe complications 4 years after CDI. Recurrence of toxinogenic CD was observed in 9 children, in 7 associated with clinical symptoms. During the last follow-up, the stool number was the same as before CDI except for 1 patient with ongoing infection.

Conclusions: CDI is more prevalent in children after ITx compared with other organ Tx; it is most often symptomatic but mildly or moderately severe. Standard antibiotics efficiently control the symptoms. Induction of rejection is a rare event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002795DOI Listing
January 2020

Short bowel syndrome in children and adults: from rehabilitation to transplantation.

Expert Rev Gastroenterol Hepatol 2019 Jan 31;13(1):55-70. Epub 2018 Oct 31.

b Gastroenterology Hepatology Nutrition Unit , Hôpital Necker-Enfants Malades , Paris , France.

Introduction: Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17474124.2019.1541736DOI Listing
January 2019

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

Liver Int 2019 06 1;39(6):1136-1146. Epub 2019 Feb 1.

Hépatologie, Gastroentérologie et Nutrition pédiatriques, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France.

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. Clinical and biological data were collected. Liver disease was classified as "severe" (portal hypertension, liver failure, liver transplantation or death); "moderate" (persistent abnormal liver biology without portal hypertension); and "mild/none" (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model.

Results: In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow-up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty-eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0-11.6): diagnosis of alpha-1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIM Z in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007).

Conclusion: Alpha-1 antitrypsin-deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non-homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14035DOI Listing
June 2019
-->