Proton pump inhibitors in esophageal atresia: A systematic review and meta-analysis.

Gastroesophageal reflux disease (GERD) is frequent and prolonged in esophageal atresia (EA) pediatric patients requiring routine use of proton pump inhibitors (PPIs). However, there are still controversies on the prophylactic use of PPIs and the efficacy of PPIs on GERD and EA complications in this special condition. The aim of the study is to assess the prophylactic use of PPIs in pediatric patients with EA and its complications. We, therefore, performed a systematic review including all reports on the subject from 1980 to 2022. We conducted meta-analysis of the pooled proportion of PPI-and no PPI groups using random effect model, meta-regression, and estimate heterogeneity by heterogeneity index I2 . Thirty-eight reports on the topic met the criteria selection, representing a cumulative 6044 patients with EA. Prophylactic PPI prescription during the first year of life does not appear to prevent GERD persistence at follow-up and is not associated with a significantly reduced rate of antireflux surgical procedures (ARP). PPIs improve peptic esophagitis and induce remission of eosinophilic esophagitis at a rate of 50%. Their effect on other GERD outcomes is uncertain. Evidence suggests that PPIs do not prevent anastomotic stricture, Barrett's esophagus, or respiratory complications. PPI use in EA can improve peptic and eosinophilic esophagitis but is ineffective on the other EA complications. Side effects of PPIs in EA are almost unknown.

Complications of one-step button percutaneous endoscopic gastrostomy in children.

To assess the complications of one-step button percutaneous endoscopic gastrostomy (B-PEG) and determine risk factors for developing stomal infections or gastropexy complications. A retrospective study of 679 children who underwent a B-PEG procedure in a single tertiary care center over a 10-year period to December 2020 was conducted. Patient characteristics, early complications (occurring ≤ 7 days after the procedure), late complications (> 7 days after the procedure), and outcomes were collected from medical records. A list of potential risk factors, including age at procedure, prematurity, underlying neurological disease, and undernutrition, was determined a priori. At least 1 year of follow-up was available for 513 patients. Median follow-up duration was 2.8 years (interquartile range 1.0-4.9 years). Major complications were rare (< 2%), and no death was related to B-PEG. Early complications affected 15.9% of the study population, and 78.0% of children presented late complications. Development of granulation tissue was the most common complication followed in frequency by tube dislodgment and T-fastener complications. Only 24 patients (3.5%) presented stomal infections. Young age at the time of PEG placement (odds ratio (OR) 2.34 [1.03-5.30], p = .042) was a risk factor for developing peristomal infection. T-fastener migration occurred in 17.3% of children, and we found underlying neurological disease was a protective factor (OR 0.59 [0.37-0.92], p = .019).  Conclusion: B-PEG is a safe method and associated with a low rate of local infection. However, T-fasteners are associated with significant morbidity and require particular attention in young and premature infants. What is Known: • Percutaneous endoscopic gastrostomy (PEG) is the preferred method to provide long-term enteral nutrition in children to prevent malnutrition. The Pull-PEG method is still the most commonly used with complications , such as stomal infection. Since its description, only a few studies have reported postoperative complications of one-step button PEG (B-PEG). What is New: • T-fastener complications were not rare, and underlying neurologic disease was a protective factor. A very low rate of stomal infection was described, and young age at the time of PEG placement was a risk factor. The B-PEG is a safe method with fewer major complications than P-PEG in children.

Endoscopic Gastrojejunostomy in Infants and Children.

OBJECTIVE: To evaluate the feasibility of endoscopic gastrojejunal tube (GJT) placement in infants and children. STUDY DESIGN: All children undergoing endoscopic GJT placement between January 2010 and December 2019 were included in this single-center retrospective study. Difficulties with and failure of GJT placement, complication rates, and device longevity, efficacy, and duration were assessed. RESULTS: A total of 107 children, median age 10 months (IQR, 5.0-23.0 months) and median weight 6.6 kg (IQR, 5.3-9.5 kg), underwent endoscopic GJT placement using the gastric stoma to introduce the endoscope (one step: n = 36 of 107; 33.6%). Endoscopic placement was successful in 99%. Eight periprocedure complications occurred, including 1 pneumoperitoneum requiring exsufflation, 2 acute pulmonary hypertension episodes leading to death in 1 case, and 5 episodes of bronchospasm. Minor complications were frequent and mostly mechanical (79%), whereas major complications were rare (5.6%): intussusception (n = 4), intestinal perforation (n = 1), and pneumoperitoneum (n = 1). Ten patients died. Of the 97 patients who lived, 85 (87%) were weaned from jejunal feeding at a median of 179 days (IQR, 69-295 days) after initiation. Among them, 30 (35.2%) required fundoplication. Weight for age z-score was significantly higher at weaning. CONCLUSIONS: GJT placement is feasible in children, even low-weight infants. Complications are frequent but are mostly minor.

Comparison of Endoscopic Dilatation and Heller's Myotomy for Treating Esophageal Achalasia in Children: A Multicenter Study.

OBJECTIVE: To compare the efficacy of, and complications from, the 2 main treatments for achalasia: endoscopic dilatation and surgical cardiomyotomy (Heller's myotomy). STUDY DESIGN: We retrospectively collected data on children treated for achalasia over an 11-year period from 8 tertiary pediatric centers. A line of treatment was defined as performing either Heller's myotomy or 1-3 sessions of endoscopy dilatation over 3 months. Treatment success was a priori defined as clinical improvement and no need for new treatment. RESULTS: Ninety-seven children (median age, 12 years; 57% boys) were included. The median time to diagnosis was 10.5 months, and the median follow-up period was 27 months. Thirty-seven children were treated by Heller's myotomy and 60 by endoscopy dilatation as the first-line treatment. After adjustment for potentially confounding factors, Heller's myotomy was significantly more successful than endoscopy dilatation (hazard ratio, 3.93 [1.74; 8.88]; P = .001), with a median survival without failure of 49 and 7 months, respectively, and with no significant difference in the occurrence of complications (35.2% for Heller's myotomy, 29.7% for endoscopy dilatation, P = .56). Hydrostatic dilatation was as successful as pneumatic dilatation (hazard ratio, 1.35 [0.56; 3.23]; P = .50). CONCLUSIONS: Heller's myotomy is more successful than endoscopy dilatation, with no significant difference in the occurrence of serious complications. This raises the potential role of peroral endoscopic myotomy as an alternative treatment to Heller's myotomy.

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study.

BACKGROUND AND AIMS: Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. APPROACH AND RESULTS: We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). CONCLUSIONS: The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

Prevalence of acid gastroesophageal reflux disease in infants with esophageal atresia/tracheoesophageal fistula.

BACKGROUND: Given the high prevalence and complication risks of acid gastroesophageal reflux (GERD) in the first months of life in infants with esophageal atresia, the ESPGHAN/NASPGHAN consensus statement recommends systematic treatment with proton pump inhibitors (PPIs) until the age of 1 year and checking for acid GERD thereafter. However, these recommendations have not been evaluated. METHODS: This prospective study was conducted from 2007 to 2016. We evaluated the prevalence of acid GERD in 100 consecutive infants presenting with esophageal atresia/tracheoesophageal fistula after the age of 18 months when PPI treatment was stopped. The diagnosis of acid GERD was based on positive pH-metry and/or evidence of complications (e.g., peptic esophagitis, need for jejunal nutrition, or antireflux surgery). Those with acid GERD at a median age of 18 months received a control examination every year or adapted to their clinical situation. RESULTS: The prevalence rates of acid GERD were 64.3% at 18 months and 22.8% at the last follow-up (median age 65 months).There is no risk factor for acid GERD identified. CONCLUSIONS: This study shows a high prevalence of acid GERD in late infancy and supports the recommendation of systematic checking for acid GERD when treatment with PPI is stopped. IMPACT: Acid gastroesophageal reflux disease (GERD) is a frequent complication of esophageal atresia in infants. The ESPGHAN/NASPGHAN consensus, which is based on expert opinion, recommends systematic treatment of children with PPI until the age of 1 year. The prevalence rates of acid GERD were 64.3% at 18 months and 22.8% at the last follow-up. This study shows a high prevalence of acid GERD in late infancy and supports the recommendation of systematic checking for acid GERD when treatment with PPI is stopped.

Risk Factors of Early Mortality and Morbidity in Esophageal Atresia with Distal Tracheoesophageal Fistula: A Population-Based Cohort Study.

OBJECTIVE: To identify the risk factors for early mortality and morbidity in a population with distal esophageal atresia (EA)-tracheoesophageal fistula. STUDY DESIGN: Cohort study from a national register. Main outcomes and measures included early mortality, hospital length of stay (LoS), need for nutritional support at 1 year of age as a proxy measure of morbidity, and complications during the first year of life. RESULTS: In total, 1008 patients with a lower esophageal fistula were included from January 1, 2008, to December 31, 2014. The survival rate at 3 months was 94.9%. The cumulative hospital LoS was 31.0 (17.0-64.0) days. Multivariate analysis showed that intrahospital mortality at 3 months was associated with low birth weight (OR 0.52, 95% CI [0.38-0.72], P < .001), associated cardiac abnormalities (OR 6.09 [1.96-18.89], P = .002), and prenatal diagnosis (OR 2.96 [1.08-8.08], P = .034). LoS was associated with low birth weight (-0.225 ± 0.035, P < .001), associated malformations (0.082 ± 0.118, P < .001), surgical difficulties (0.270 ± 0.107, P < .001), and complications (0.535 ± 0.099, P < .001) during the first year of life. Predictive factors for dependency on nutrition support at 1 year of age were complications before 1 year (OR 3.28 [1.23-8.76], P < .02) and initial hospital LoS (OR 1.96 [1.15-3.33], P < .01). CONCLUSIONS: EA has a low rate of early mortality, but morbidity is high during the first year of life. Identifying factors associated with morbidity may help to improve neonatal care of this population.

Comparison of Symptom Control in Pediatric Gastroparesis Using Endoscopic Pyloric Botulinum Toxin Injection and Dilatation.

OBJECTIVES: The objective of this study was to assess the tolerance and efficacy of endoscopic intrapyloric botulinum toxin injection compared with pyloric dilatation in children with gastroparesis. METHODS: This was a retrospective descriptive multicentre study that included pediatric patients treated between 2010 and 2018 at 4 tertiary hospitals. RESULTS: Data were collected for 24 patients. The median age at diagnosis was 2.5 years (range 0.5-4.7). A total of 46 endoscopic procedures were performed. The endoscopic procedure was multiple in 63% of patients. Among the interventions, 76% were successful and 15% were unsuccessful. The recurrence rate was 57% and the median time to recurrence was 3.7 months (0.1-73). The efficacy did not differ significantly between the 2 methods at the first intervention and as a second-line treatment. The recurrence rate also did not differ significantly between the 2 methods. No complications were reported. The median follow-up was 19.8 months (1.7-61.7). CONCLUSIONS: In this retrospective multicentre study, endoscopic management of gastroparesis by balloon dilatation or botulinum toxin was safe in children and seemed to be partially efficient within the first months. Symptoms recurred frequently and required repetition of the interventions.

Factors Associated With Success and Failure of Weaning Children From Prolonged Enteral Nutrition: A Retrospective Cohort Study.

OBJECTIVES: The aims of the present study were to assess the efficacy of a tube weaning program, and to identify factors associated with success and failure. METHODS: This was a retrospective cohort study including all pediatric patients on enteral nutrition (EN) for ≥6 months for whom at least 1 attempt of weaning was performed in a single tertiary referral center from 2012 to 2017, with a minimum follow-up of 6 months after EN discontinuation. Weaning program was individualized to each child. Weaning success was defined a priori. Factors associated with success were investigated using multivariate analysis. RESULTS: Ninety-four patients were enrolled, in whom a total of 114 attempts of weaning were performed at a median age of 51 ±â€Š40 months. Success was achieved in 80 attempts (success rate of 70%). One hundred three (92%) weaning attempts were performed at home with a follow-up in the outpatient clinic, mostly (74%) by a progressive (>1 month) reduction of tube feeding. Patients who required psychological support during weaning had more failures than patients who did not (odds ratio = 5.7, 95% confidence interval [1.2-27.0], P = 0.03). The presence of impaired oral feeding skills at the time of EN discontinuation was also predictive of failure (odds ratio = 6.2, 95% confidence interval [0.05-0.5], P = 0.005). CONCLUSIONS: Our progressive, mostly outpatient-based, patient-tailored program of weaning from EN is effective for tube-dependent children. Children who need psychological support during weaning and those who present impaired oral feeding skills represent a subgroup of at-risk patients for whom alternative weaning strategies may need to be considered.

Frequency of Abnormal Glucose Tolerance Test Suggestive of Dumping Syndrome Following Oesophageal Atresia Repair.

OBJECTIVES: Dumping syndrome (DS) is mostly described as a complication of antireflux surgery in oesophageal atresia (OA) but we previously reported 2 cases of DS before any other surgery in infants operated at birth for OA. The objectives of the present study were to assess the prevalence of abnormal oral glucose tolerance test (OGTT) at 3 months of age in infants operated at birth with type C OA, to describe symptoms and clinical features, and to assess risk factors in infants presenting with abnormal OGTT suggestive of DS. METHODS: A prospective case series study including infants with type C OA without fundoplication, born between 2013 and 2016 in 8 centres was conducted. An OGTT was performed between 2.5 and 3.5 months. Abnormal OGTT was defined as early hyperglycaemia (>1.8 g/L until 30 minutes; >1.7 g/L between 30 minutes and 2 hours; and >1.4 g/L between 2 and 3 hours) and/or late hypoglycaemia (<0.6 g/L after 2 hours). RESULTS: Eleven of the 38 OGTT (29%) showed abnormalities. None of the patients' demographics (birth weight, sex, prematurity, associated malformation, use of enteral nutrition) or conditions of the surgery tested was associated with abnormal OGTT. No clinical sign was specific for it. CONCLUSIONS: DS should be considered in every infant operated at birth for OA presenting with digestive symptoms. No risk factor was predictive for abnormal OGTT. An OGTT to screen for potential DS around 3 months of age should be considered in infants born with EA. CLINICAL TRIAL NAME AND REGISTRATION NUMBER: DUMPING NCT02525705.

Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis: Data From the Pediatric Primary Sclerosing Cholangitis Consortium.

OBJECTIVES: Most patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The liver and colon express MAdCAM-1, a target of lymphocyte homing integrins. Vedolizumab (VDZ) is an α4ß7 integrin antibody used to treat IBD. We investigated liver outcomes in children with PSC-IBD treated with VDZ. METHODS: Patients were identified within the Pediatric PSC Consortium, a multicenter research registry. Retrospective demographic, phenotypic, biochemical, radiological, histopathologic and IBD data for up to 1 year of VDZ therapy were collected. Liver biochemical and IBD responses were defined as: a 75% or greater reduction in initial γ-glutamyltransferase (GGT), or a GGT that fell to <50 IU/L and improved Mayo endoscopy grade or IBD activity scores after 9 to 12 months. RESULTS: Thirty-seven patients were identified from 19 centers. VDZ was initiated at median age of 16 years [IQR 15-18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response after 9 to 12 months. For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response. Final GGT after 9 to 12 months was 51 [IQR 28-71] in IBD patients in remission versus 127 [IQR 63-226] in those with active IBD, (P = 0.066). CONCLUSIONS: Liver biochemistry worsened over time in IBD unresponsive to VDZ but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically refractory IBD.

Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children.

BACKGROUND: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. METHODS: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. RESULTS: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. CONCLUSIONS: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.

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. 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, PIMlike 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.

Prevalence of Eosinophilic Esophagitis in Adolescents With Esophageal Atresia.

BACKGROUND AND OBJECTIVE: Eosinophilic esophagitis (EoE) is an increasingly recognized childhood disease. Esophageal atresia (EA) is the most frequent congenital malformation of the esophagus. Recently, cases of EoE occurring in patients with EA have been reported, although the exact prevalence of EoE in EA remains unknown. The aim is to investigate the prevalence of EoE among EA in adolescents and to describe these patients' characteristics. METHODS: Systematic upper gastrointestinal endoscopies with multistage esophageal biopsies were prospectively performed in 63 adolescents with EA. A standardized form was used to collect clinical and endoscopic data. Diagnosis of EoE was made as ≥15 intraepithelial eosinophils/high power field, whatever the response on proton pump inhibitors therapy. RESULTS: Six patients (9.5%) presented an EoE (17-100 eosinophils/high power field). An atopic condition was reported more frequently in the eosinophil ≥15 group than in patients with no EoE (66% vs 16%; P = 0.014). Except for chest pain, symptoms and endoscopic features were similar in patients with EoE and patients with no EoE. CONCLUSION: In our series of 63 patients born with EA, mainly distal tracheoesophageal fistula, the prevalence of EoE is increased, and therefore should be considered in adolescents with EA.

Influence of Percutaneous Endoscopic Gastrostomy on Gastroesophageal Reflux Disease in Children.

OBJECTIVE: To determine if gastroesophageal reflux disease (GERD) is present at long-term follow-up after percutaneous endoscopic gastrostomy (PEG), and to identify factors associated with the occurrence or aggravation of GERD after PEG placement. STUDY DESIGN: This prospective, observational study was conducted in our single tertiary center over a 13-year period (gastrostomy performed from 1990 to 2003 and follow-up to 2015). Every child who underwent PEG in our center (N = 368) from 1990 to 2003 was eligible. GERD was defined by clinical manifestations requiring antisecretory or prokinetic treatment, occurrence of a GERD-related complication, or the need for antireflux surgery. Outcomes among patients without antireflux surgery were also assessed. Multivariate analysis was used to identify factors aggravating GERD after PEG placement. RESULTS: A total 326 patients (89%; 56% with a neurologic impairment) were studied with a median follow-up after 3.5 years (range, 2.0-13.5 years). After PEG placement, GERD appeared in 11% of patients and was aggravated in 25% of patients with preexisting GERD. Factors associated with GERD worsening after PEG placement were neurologic impairment and preexisting GERD. Only 53 patients (16%) required antireflux surgery, among whom 22 required surgery in the year after PEG. Neurologic impairment was the only factor significantly associated with the need for antireflux surgery. CONCLUSIONS: GERD predominantly remains clinically controlled after PEG placement. Routine antireflux surgery at the time of PEG placement is not justified.

The French Experience with a Population-Based Esophageal Atresia Registry (RENATO).

This paper presented a national register for esophageal atresia (EA) started in January 2008. We report our experience about the conception of this database and its coordination. Data management and data quality are also detailed. In 2023, more than 2,500 patients with EA are included. Prevalence of EA in France was calculated at 1.8/10,000 live birth. Main clinical results are listed with scientific publications issued directly from the register.

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). Eligible patients had a genetically confirmed diagnosis of Alagille syndrome, a history of significant pruritus, and elevated serum bile acids. Patients were randomly assigned (2:1) to receive oral odevixibat 120 µg/kg per day or placebo for 24 weeks (in a block size of six and stratified by age: <10 years and ≥10 years to <18 years) via a web-based system. Patients, clinicians, study staff, and people analysing the data were masked to treatment allocation. The primary efficacy endpoint was change in caregiver-reported scratching score (on the PRUCISION instrument; range 0-4) from baseline to weeks 21-24. The prespecified key secondary efficacy endpoint was change in serum bile acid concentration from baseline to the average of weeks 20 and 24. Outcomes were analysed in patients who received at least one dose of study drug (the full analysis set for efficacy outcomes and the safety analysis set for safety outcomes). This trial is registered on ClinicalTrials.gov (NCT04674761) and EudraCT (2020-004011-28), and is completed. FINDINGS: Between Feb 26, 2021, and Sept 9, 2022, 52 patients were randomly assigned to receive odevixibat (n=35) or placebo (n=17), all of whom were included in the analysis sets. The median age was 5·5 years (IQR 3·2 to 8·9). 27 (52%) of 52 patients were male and 25 (48%) were female. The mean scratching score was elevated at baseline in both groups (2·8 [SD 0·5] for odevixibat vs 3·0 [0·6] for placebo). Mean scratching scores at weeks 21-24 were 1·1 (0·9) for odevixibat and 2·2 (1·0) for placebo, representing a least-squares (LS) mean change of -1·7 (95% CI -2·0 to -1·3) for odevixibat and -0·8 (-1·3 to -0·3) for placebo, which was significantly greater for odevixibat than for placebo (difference in LS mean change from baseline -0·9 [95% CI -1·4 to -0·3]; p=0·0024). Odevixibat also resulted in significantly greater reductions in mean serum bile acids from baseline versus placebo (237 µmol/L [SD 115] with odevixibat vs 246 µmol/L [121] with placebo) to the average of weeks 20 and 24 (149 µmol/L [102] vs 271 µmol/L [167]; LS mean change -90 µmol/L [95% CI -133 to -48] with odevixibat vs 22 µmol/L [-35 to 80] with placebo; difference in LS mean change -113 µmol/L [95% CI -179 to -47]; p=0·0012). The most common treatment-emergent adverse events were diarrhoea (ten [29%] of 35 patients in the odevixibat group vs one [6%] of 17 in the placebo group) and pyrexia (eight [23%] vs four [24%]). Seven patients had serious treatment-emergent adverse events during the treatment period: five (14%) in the odevixibat group and two (12%) in the placebo group. No patients discontinued treatment and there were no deaths. INTERPRETATION: Odevixibat could be an efficacious non-surgical intervention to improve pruritus, reduce serum bile acids, and enhance the standard of care in patients with Alagille syndrome. Longer-term safety and efficacy data of odevixibat in this population are awaited from the ongoing, open-label ASSERT-EXT study. FUNDING: Albireo Pharma, an Ipsen company.