Publications by authors named "Bart G P Koot"

52 Publications

Late hepatic toxicity surveillance for survivors of childhood, adolescent and young adult cancer: Recommendations from the international late effects of childhood cancer guideline harmonization group.

Cancer Treat Rev 2021 Nov 20;100:102296. Epub 2021 Sep 20.

Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.

Background: Survivors of childhood, adolescent and young adult (CAYA) cancer may develop treatment-induced chronic liver disease. Surveillance guidelines can improve survivors' health outcomes. However, current recommendations vary, leading to uncertainty about optimal screening. The International Late Effects of Childhood Cancer Guideline Harmonization Group has developed recommendations for the surveillance of late hepatotoxicity after CAYA cancer.

Methods: Evidence-based methods based on the GRADE framework were used in guideline development. A multidisciplinary guideline panel performed systematic literature reviews, developed evidence summaries, appraised the evidence, and formulated recommendations on the basis of evidence, clinical judgement, and consideration of benefits versus the harms of the surveillance while allowing for flexibility in implementation across different health care systems.

Results: The guideline strongly recommends a physical examination and measurement of serum liver enzyme concentrations (ALT, AST, gGT, ALP) once at entry into long-term follow-up for survivors treated with radiotherapy potentially exposing the liver (moderate- to high-quality evidence). For survivors treated with busulfan, thioguanine, mercaptopurine, methotrexate, dactinomycin, hematopoietic stem cell transplantation (HSCT), or hepatic surgery, or with a history of chronic viral hepatitis or sinusoidal obstruction syndrome, similar surveillance for late hepatotoxicity once at entry into LTFU is reasonable (low-quality evidence/expert opinion, moderate recommendation). For survivors who have undergone HSCT and/or received multiple red blood cell transfusions, surveillance for iron overload with serum ferritin is strongly recommended once at long-term follow-up entry.

Conclusions: These evidence-based, internationally-harmonized recommendations for the surveillance of late hepatic toxicity in cancer survivors can inform clinical care and guide future research of health outcomes for CAYA cancer survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ctrv.2021.102296DOI Listing
November 2021

Identifying the Genetics Underlying Nonalcoholic Fatty Liver Disease: A Quest That is Far From Over.

J Pediatr Gastroenterol Nutr 2021 08;73(2):139-140

Department of Clinical Genetics, Amsterdam University Medical Centers, Location Vumc.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003180DOI Listing
August 2021

Intestinal Ultrasound in Pediatric Inflammatory Bowel Disease: Promising, but Work in Progress.

Inflamm Bowel Dis 2021 May 20. Epub 2021 May 20.

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Amsterdam, The Netherlands.

Intestinal ultrasound (IUS) is increasingly used and promulgated as a noninvasive monitoring tool for children with inflammatory bowel disease because other diagnostic modalities such as colonoscopy and magnetic resonance imaging cause significant stress in the pediatric population. The most important parameters of inflammation that can be assessed using IUS are bowel wall thickness and hyperemia of the bowel wall. Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited. This review gives an update and overview of the current evidence on the use and accuracy of IUS in children with inflammatory bowel disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ibd/izab125DOI Listing
May 2021

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

Hepatology 2021 Oct 9;74(4):2047-2057. Epub 2021 Sep 9.

Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31911DOI Listing
October 2021

Diagnostic accuracy of fibrosis tests in children with non-alcoholic fatty liver disease: A systematic review.

Liver Int 2021 09 11;41(9):2087-2100. Epub 2021 May 11.

Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Academic Medical Center, Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non-invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non-invasive methods for staging liver fibrosis in children with NAFLD.

Methods: We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood-based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard.

Results: Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta-analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis.

Conclusion: Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453517PMC
September 2021

Non-radiologist-performed abdominal point-of-care ultrasonography in paediatrics - a scoping review.

Pediatr Radiol 2021 Jul 10;51(8):1386-1399. Epub 2021 Apr 10.

Amsterdam UMC, Radiology, University of Amsterdam, Amsterdam, The Netherlands.

Background: Historically, US in the paediatric setting has mostly been the domain of radiologists. However, in the last decade, there has been an uptake of non-radiologist point-of-care US.

Objective: To gain an overview of abdominal non-radiologist point-of-care US in paediatrics.

Materials And Methods: We conducted a scoping review regarding the uses of abdominal non-radiologist point-of-care US, quality of examinations and training, patient perspective, financial costs and legal consequences following the use of non-radiologist point-of-care US. We conducted an advanced search of the following databases: Medline, Embase and Web of Science Conference Proceedings. We included published original research studies describing abdominal non-radiologist point-of-care US in children. We limited studies to English-language articles from Western countries.

Results: We found a total of 5,092 publications and selected 106 publications for inclusion: 39 studies and 51 case reports or case series on the state-of-art of abdominal non-radiologist point-of-care US, 14 on training of non-radiologists, and 1 each on possible harms following non-radiologist point-of-care US and patient satisfaction. According to included studies, non-radiologist point-of-care US is increasingly used, but no standardised training guidelines exist. We found no studies regarding the financial consequences of non-radiologist point-of-care US.

Conclusion: This scoping review supports the further development of non-radiologist point-of-care US and underlines the need for consensus on who can do which examination after which level of training among US performers. More research is needed on training non-radiologists and on the costs-to-benefits of non-radiologist point-of-care US.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00247-021-04997-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266706PMC
July 2021

Exome sequencing in patient-parent trios suggests new candidate genes for early-onset primary sclerosing cholangitis.

Liver Int 2021 05 11;41(5):1044-1057. Epub 2021 Mar 11.

Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background & Aims: Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC ≤ 12 years to investigate the contribution of rare genetic variants to early-onset PSC.

Methods: In this multicentre study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency < 2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function.

Results: In 22 of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harbouring a total of 54 variants with predicted pathogenic effects. In 18 genes, we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function.

Conclusions: The 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252477PMC
May 2021

Reply to "Rapid Infliximab Infusions in Paediatric Inflammatory Bowel Disease Patients, a Single Hospital Experience".

J Pediatr Gastroenterol Nutr 2021 02;72(2):e56

Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development; Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002998DOI Listing
February 2021

Fool me once… treatment exposure to achieve remission in pediatric IBD.

Eur J Pediatr 2020 12;179(12):1921-1924

Department of Pediatrics, Spaarne Gasthuis, Hoofddorp, Haarlem, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-020-03862-7DOI Listing
December 2020

Can 2 Different Fecal Calprotectin Assays be Used Interchangeably in IBD Treatment?

J Clin Gastroenterol 2020 Oct 27. Epub 2020 Oct 27.

Departments of Pediatric Gastroenterology, Emma Children's Hospital.

Background: Fecal calprotectin (FC) is a biomarker for inflammation in inflammatory bowel disease (IBD). Interpretation of results can be complicated because of the use of different assays to determine FC.

Goals: To assess the agreement between 2 different assays for determining FC in patients with IBD.

Methods: Samples from adults and children with IBD were tested with 2 assays: (1) EliA 2 Calprotectin and (2) EK-Cal. Samples were uniformly tested on the same day. Interassay variability was displayed in a Bland-Altman plot. The difference in categorization of the FC result (1: 0 to 250 mg/kg, 2: 250 to 500 mg/kg, 3: >500 mg/kg) was assessed with the linear weighted κ for adults and children separately.

Results: A total of 171 patients [mean age: 33 (range: 7 to 81); 92 (54%) female; 117 (68%) Crohn's disease; 53 (31%) ulcerative colitis] were included. Median (interquartile ranges) FC levels were 281 mg/kg (70 to 971) (EK-Cal) and 159 mg/kg (31 to 778) (EliA 2), and the mean delta FC was 89 mg/kg. In the adult population, there was substantial agreement between the 2 assays (κ: 0.72; SE: 0.06; 95% confidence interval, 0.60-0.83) and for pediatric patients, the agreement was almost perfect (κ: 0.83; SE: 0.06; 95% confidence interval: 0.70-0.95). Five of 171 patients (all aged ≥17 y and all with colonic disease) had a difference of 2 categories (1 vs. 3) between assays. Interassay variability was the highest in category 3.

Conclusions: The agreement between the EliA 2 and EK-Cal assay in this cohort of IBD patients is substantial to almost perfect. Interassay variability is higher in the highest FC category.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCG.0000000000001460DOI Listing
October 2020

Lipidomics in Nonalcoholic Fatty Liver Disease: Exploring Serum Lipids as Biomarkers for Pediatric Nonalcoholic Fatty Liver Disease.

J Pediatr Gastroenterol Nutr 2020 10;71(4):433-439

Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital, University of Amsterdam.

Objectives: Disturbances in lipid metabolism play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Using lipidomics, an analytical technique that is used to broadly survey lipid metabolism, we searched for biomarkers in plasma that are correlated with the presence of hepatic steatosis in children with obesity.

Methods: Lipidomics was performed in plasma samples of 21 children with obesity in whom steatosis was detected using proton magnetic resonance spectroscopy (H-MRS) and were compared with the lipidome of 21 samples of nonsteatotic subjects with obesity.

Results: Forty-two samples were analyzed (57% boys; median age 15 years). A total of 18 lipid classes constituting 839 different lipid species were identified. A statistically significant increase in alkyldiacylglycerol (TG[O]) and phosphatidylethanolamine (PE) species and a significant decrease in alkyl/alkenyl-phosphatidylethanolamine (PE[O]), alkyl/alkenyl-lysophosphatidylethanolamine (LPE[O]) and alkyl/alkenyl-phosphatidylcholine (PC[O]) was observed in children with hepatic steatosis compared with controls. Twelve individual lipid species of 3 lipid classes were significantly increased in steatotic subjects compared with controls.

Conclusions: In this pilot study, we found statistically significant alterations in 5 major lipid classes and 12 individual lipid species in children with steatosis. These might be potential biomarkers for pediatric NAFLD. Lipidomic studies in larger cohorts of children are needed to determine the diagnostic value of these lipids and determine whether results can be generalized for different age groups and ethnic backgrounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002875DOI Listing
October 2020

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

Hepatology 2021 03;73(3):1061-1073

Massachusetts General Hospital, Harvard Medical School, Boston, MA.

Background And Aims: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes.

Approach And Results: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis.

Conclusions: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31560DOI Listing
March 2021

Accuracy of controlled attenuation parameter compared with ultrasound for detecting hepatic steatosis in children with severe obesity.

Eur Radiol 2021 Mar 10;31(3):1588-1596. Epub 2020 Sep 10.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Objectives: To determine the diagnostic accuracy of controlled attenuation parameter (CAP) on FibroScan in detecting and grading steatosis in a screening setting and perform a head-to-head comparison with conventional B-mode ultrasound.

Methods: Sixty children with severe obesity (median BMI z-score 3.37; median age 13.7 years) were evaluated. All underwent CAP and US using a standardized scoring system. Magnetic resonance spectroscopy proton density fat fraction (MRS-PDFF) was used as a reference standard.

Results: Steatosis was present in 36/60 (60%) children. The areas under the ROC (AUROC) of CAP for the detection of grade ≥ S1, ≥ S2, and ≥ S3 steatosis were 0.80 (95% CI: 0.67-0.89), 0.77 (95% CI: 0.65-0.87), and 0.79 (95% CI: 0.66-0.88), respectively. The AUROC of US for the detection of grade ≥ S1 steatosis was 0.68 (95% CI: 0.55-0.80) and not significantly different from that of CAP (p = 0.09). For detecting ≥ S1 steatosis, using the optimal cutoffs, CAP (277 dB/m) and US (US steatosis score ≥ 2) had a sensitivity of 75% and 61% and a specificity of 75% and 71%, respectively. When using echogenicity of liver parenchyma as only the scoring item, US had a sensitivity of 70% and specificity of 46% to detect ≥ S1 steatosis. The difference in specificity of CAP and US when using only echogenicity of liver parenchyma of 29% was significant (p = 0.04).

Conclusion: The overall performance of CAP is not significantly better than that of US in detecting steatosis in children with obesity, provided that the standardized scoring of US features is applied. When US is based on liver echogenicity only, CAP outperforms US in screening for any steatosis (≥ S1).

Key Points: • The areas under the ROC curves of CAP and ultrasound (US) for detecting grade ≥ S1 steatosis were 0.80 and 0.68, respectively, and were not significantly different (p = 0.09). • For detecting grade ≥ S1 steatosis in severely obese children, CAP had a sensitivity of 75% and a specificity of 75% at its optimal cutoff value of 277 dB/m. • For detecting grade ≥ S1 steatosis in clinical practice, both CAP and US can be used, provided that the standardized scoring of US images is used.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-07245-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880971PMC
March 2021

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

J Pediatr Gastroenterol Nutr 2020 10;71(4):459-464

University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, UT.

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 α4β7 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002855DOI Listing
October 2020

The prevalence of liver fibrosis according to non-invasive tools in a pediatric home parenteral nutrition cohort.

Clin Nutr 2021 02 11;40(2):460-466. Epub 2020 Jun 11.

Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Amsterdam, the Netherlands.

Background & Aims: Liver biopsy is no viable tool to routinely screen for liver fibrosis in children suffering from chronic intestinal failure (IF). We aim to assess the prevalence of liver fibrosis in a cohort of children with chronic IF by non-invasive tests: transient elastography (TE), aspartate-aminotransferase-to-platelet-ratio-index (APRI) and enhanced liver fibrosis (ELF) score.

Methods: Cross sectional study where patients with chronic IF, receiving parenteral nutrition (PN) for at least 3 months, were enrolled. TE, APRI and ELF score were measured. Using Spearman's rank correlation coefficient and Kruskal-Wallis H test, the correlation between TE, APRI, ELF score and known risk factors for development of intestinal failure-associated liver disease (IFALD) were calculated.

Results: 32 patients were included (50% female), median age was 8 years and 4 months, median PN duration was 45 months. Six patients (21%) had TE ≥6.5 kPa, indicating significant fibrosis. Twelve patients (38%) had APRI ≥.5, indicating fibrosis. ELF score indicated moderate fibrosis in 17 patients (63%) and significant fibrosis in 10 patients (37%). TE and APRI correlated significantly with known risk factors for IFALD, but ELF showed poor correlation with known risk factors for IFALD.

Conclusion: In a cohort of pediatric patients suffering from chronic IF, TE measurement, APRI and ELF test show a varying, but substantial proportion of subjects with fibrosis. The diagnostic value of these tests and their role in the management of pediatric IF must be determined in larger cohorts with liver biopsy as reference standard.

Trial Registration: Academic Medical Center medical ethics committee number: METC 2017_185.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2020.05.039DOI Listing
February 2021

Safety of Rapid Infliximab Infusions in Children: A Systematic Review.

J Pediatr Gastroenterol Nutr 2020 09;71(3):361-365

Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development.

Objectives: The aim of the study was to assess whether the incidence of infusion reactions (IR) increases after rapid (≤1 hour) infliximab (IFX) infusions, compared with standard (2-3 hour) infusions in children.

Methods: Systematic review including studies describing the number of IR after rapid IFX infusion in children ages 0 to 18 years.

Results: Four records were included (3 retrospective, n = 498, 347 standard infusions, 3703 rapid infusions). Reported incidences of IR ranged from 0% to 2% of infusions in standard groups (reported 95% confidence intervals [CIs] ranged from 0% to 7%) and from 0% to 2% of infusions in rapid groups (reported 95% CIs ranged from 0% to 12%). None of the studies included reported a significant difference in incidence of IR between the 2 groups.

Conclusions: There is insufficient evidence to conclude whether the rate of IR after rapid IFX increases. The consistent finding of no increase in IR in all studies and the low rate of observed IR suggests there is no significant difference in rate of IR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002815DOI Listing
September 2020

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

Hepatology 2021 03 19;73(3):1074-1087. Epub 2020 Dec 19.

Boston Children's Hospital and Harvard Medical School, Boston, MA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31393DOI Listing
March 2021

Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis.

Clin Gastroenterol Hepatol 2021 05 29;19(5):1067-1070.e2. Epub 2020 Apr 29.

Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.

Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC). We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2020.04.055DOI Listing
May 2021

Endoscopic Retrograde Cholangiopancreatography in Infants: Availability Under Threat: A Survey on Availability, Need, and Clinical Practice in Europe and Israel.

J Pediatr Gastroenterol Nutr 2020 08;71(2):e54-e58

Liver Unit, Birmingham Women's and Children's Hospital, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham.

Endoscopic retrograde cholangiopancreatography (ERCP) in infants (younger than 1 year of age) is a highly specialized procedure. Since 2014 opportunities to maintain or purchase duodenoscopes for ERCP in infants have disappeared. In a survey among European hepatology centers (including Israel) we evaluated the availability, need, indications, and practice of ERCP procedures in infants. It shows that infant ERCP is a low-volume procedure (median 5 procedures/year) in the 14 centers that perform this procedure. Since 2014 several centers no longer have an infant ERCP duodenoscope due to breakdown. In addition, substantial differences exist between centers in indications, types of interventions performed, and practical execution of ERCP procedures in infants. We conclude that a concerted effort by the pediatric hepatology community is needed to secure the future availability of infant ERCP. In addition, consensus on the indications and optimal use of infant ERCP could improve the quality of ERCP care for infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002752DOI Listing
August 2020

Survey on screening for paediatric non-alcoholic fatty liver disease in clinical practice in Dutch hospitals.

Acta Paediatr 2020 11 20;109(11):2388-2393. Epub 2020 Apr 20.

Department of Paediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Location Academic Medical Center, Emma Children's Hospital, Amsterdam, The Netherlands.

Aim: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease that affects 34% of children with obesity. Besides the liver-related morbidity, NAFLD also increases the risk of cardiometabolic diseases at adult age. Diverse screening recommendations exist on paediatric NAFLD. The aim of this study was to assess screening practices among paediatricians managing children with obesity in the Netherlands.

Methods: Between 2016 and 2017, an Internet-based survey was sent to all 167 members of the endocrinology section of the Dutch Paediatricians Society, that includes all paediatricians involved in obesity care. Descriptive statistics (frequencies) were used to analyse responses.

Results: In total, 42/167 (25%) of the invited paediatricians responded. Thirty-six of 42 respondents (86%) screen for NAFLD. One-third of those do not follow any guideline. Most respondents use ALT as screening tool, with thresholds varying between 21-80 IU/L. The majority (29/36) indicate they lack guidance on screening and follow-up.

Conclusion: In this study sample of Dutch paediatricians, screening for paediatric NAFLD is widely, albeit not universally, performed and in a highly variable way. This underlines the need come to a uniform and comprehensive screening strategy and raise awareness about NAFLD among physicians treating children with obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apa.15294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687083PMC
November 2020

Do Antibiotics Reduce the Incidence of Infections After Percutaneous Endoscopic Gastrostomy Placement in Children?

J Pediatr Gastroenterol Nutr 2020 07;71(1):23-28

Pediatric Gastroenterology.

Objective: Percutaneous endoscopic gastrostomy (PEG) provides a long-term solution for tube dependency. Pediatric guidelines recommend prophylactic antibiotic treatment (ABT) based on adult studies.

Aim: To compare wound infection and other complications in children receiving a PEG with and without prophylactic ABT.

Methods: Retrospective study including children 0 to 18 years undergoing PEG placement. Patients with (2010-2013) and without (2000-2010) ABT were compared with respect to the occurrence of wound infection and other complications.

Results: In total, 297 patients were included (median age 2.9 years, 53% boys). Patients receiving ABT per PEG protocol (n = 78) had a similar wound infection rate (17.9% vs 21%, P = 0.625), significantly less fever (3.8% vs 14.6%, P = 0.013), leakage (0% vs 9.1%, P = 0.003) and shorter hospital admission (2 vs 4 days, P = 0.000), but more overgranulation (28.2% vs 8.7%, P = 0.000) compared with those without (n = 219). Patients receiving any ABT, per PEG protocol or clinical indication (n = 115), had similar occurrence of wound infection (19.1% vs 20.9%, P = 0.768), fever (7.8% vs 14.3%, P = 0.100) and leakage (3.5% vs 8.8%, P = 0.096), a significantly shorter hospital admission (3 vs 4 days, P = 0.000), but more overgranulation (21.7% vs 8.8%, P =0.003) compared with those without (n = 182).

Conclusions: Prophylactic ABT does not seem to reduce the occurrence of wound infection but it might be beneficial with respect to fever, leakage and duration of hospital admission, but not overgranulation. A randomized controlled trial is needed to confirm our results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002709DOI Listing
July 2020

Bowel ultrasound measurements in healthy children - systematic review and meta-analysis.

Pediatr Radiol 2020 04 14;50(4):501-508. Epub 2019 Dec 14.

Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Ultrasound (US) is a noninvasive method of assessing the bowel that can be used to screen for bowel pathology, such as Inflammatory Bowel Disease, in children. Knowledge about US findings of the bowel in healthy children is important for interpreting US results in cases where disease is suspected.

Objective: To assess the bowel wall thickness in different bowel segments in healthy children and to assess differences in bowel wall thickness among pediatric age categories.

Materials And Methods: We conducted a systematic search in the PubMed, Embase, Cochrane, and CINAHL databases for studies describing bowel wall thickness measured by transabdominal US in healthy children. We excluded studies using contrast agent. We calculated the pooled mean and standard deviation scores and assessed differences among age categories (0-4 years, 5-9 years, 10-14 years, 15-18 years), first with analysis of variance (ANOVA) and further with subsequent Student's t-tests for independent samples, corrected for multiple testing.

Results: We identified 191 studies and included 7 of these studies in the systematic review. Reported bowel wall thickness values ranged from 0.8 mm to 1.9 mm in the small bowel and from 1.0 mm to 1.9 mm in the colon. The mean colonic bowel wall thickness is larger in children ages 15-19 years compared to 0-4 years (range in difference: 0.3-0.5 mm [corrected P<0.02]).

Conclusion: The reported upper limit of bowel wall thickness in healthy children is 1.9 mm in the small bowel and the colon, and mean thickness increases slightly with age in jejunum and colon. These values can be used as guidance when screening for bowel-related pathology in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00247-019-04567-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067709PMC
April 2020

The current status of non-radiologist-performed abdominal ultrasonography in paediatrics - a scoping literature review protocol.

Pediatr Radiol 2019 09 27;49(10):1249-1252. Epub 2019 Aug 27.

Department of Radiology, Emma Children's Hospital - Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam Zuid-Oost, the Netherlands.

In recent years as a result of decreasing prices and the increasing availability of portable systems, ultrasonography (US), which historically has primarily been the domain of radiologists, has become more widely available to non-radiologists as well. This has increased the use of point-of-care paediatric US performed by non-radiologists. With this scoping review, focused on abdominal imaging, we aim to gain an overview of the current practices in the paediatric setting and to assess its impact in daily practice. We present the background and study design of a scoping review for non-radiologist-performed abdominal point-of-care paediatric US using a formal scoping framework. The information shall be derived from published studies. We will submit the review report to a peer-reviewed scientific journal and explore other scientific venues for presenting the work. Based on the completed review, the officers of the European Society of Paediatric Radiology will issue a position statement on non-radiologist-performed point-of-care paediatric US.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00247-019-04452-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710212PMC
September 2019

Premedication with intravenous steroids does not influence the incidence of infusion reactions following infliximab infusions in pediatric inflammatory bowel disease patients-a case-control study.

Eur J Clin Pharmacol 2019 Oct 22;75(10):1445-1450. Epub 2019 Jul 22.

Emma Children's Hospital, Amsterdam UMC, Pediatric Gastroenterology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Purpose: Infusion reactions (IR) are commonly described side effects of infliximab (IFX) infusions, often leading to discontinuation of IFX. This study aimed to investigate the influence of steroid premedication (PM) on incidence of IR in pediatric inflammatory bowel disease (PIBD) patients receiving IFX.

Methods: A case-control study in two tertiary centers in Amsterdam, The Netherlands, including PIBD patients receiving IFX. PM with steroids was part of standard care in one center (PM+) but not in the other center (PM-). Acute IR were divided into mild/severe reactions and in grade 1/2/3/4 for detailed exploration. Differences between subgroups were assessed with the T or chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage.

Results: We included 226 patients (91 PM+, 50% male, mean age at onset of IBD 12.7 years), receiving 3433 infusions. There was no difference between the PM+ and PM- subgroups in incidence of IR (14.3% vs. 17.0% of patients, p = 0.58) and in percentage of infusions followed by IR (1.4% in both subgroups). The OR of developing IR when using PM was 1.06 (95% CI 0.49-2.27, p = 0.89), and the OR of developing a grade 3 or 4 IR when using PM was 0.90 (95% CI 0.24-3.39, p = 0.88) when correcting for co-medication usage.

Conclusion: The incidence of IR was low, and premedication with steroids did not decrease the incidence of IR in this cohort of PIBD patients receiving IFX. Our results indicate that PM with steroids is not indicated in PIBD to prevent IR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00228-019-02715-zDOI Listing
October 2019

Diagnostic Accuracy of Transabdominal Ultrasound in Detecting Intestinal Inflammation in Paediatric IBD Patients-a Systematic Review.

J Crohns Colitis 2019 Dec;13(12):1501-1509

Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Gastroenterology, Amsterdam, The Netherlands.

Background And Aims: Currently used non-invasive tools for monitoring children with inflammatory bowel disease [IBD], such as faecal calprotectin, do not accurately reflect the degree of intestinal inflammation and do not provide information on disease location. Ultrasound [US] might be of added value. This systematic review aimed to assess the diagnostic test accuracy of transabdominal US in detecting intestinal inflammation in children with IBD in both diagnostic and follow-up settings.

Methods: We systematically searched PubMed, Embase [Ovid], Cochrane Library, and CINAHL [EBSCO] databases for studies assessing diagnostic accuracy of transabdominal US for detection of intestinal inflammation in patients diagnosed or suspected of IBD, aged 0-18 years, with ileo-colonoscopy and/or magnetic resonance enterography [MRE] as reference standards. Studies using US contrast were excluded. Risk of bias was assessed with QUADAS-2.

Results: The search yielded 276 records of which 14 were included. No meta-analysis was performed, because of heterogeneity in study design and methodological quality. Only four studies gave a clear description of their definition for an abnormal US result. The sensitivity and specificity of US ranged from 39-93% and 90-100% for diagnosing de novo IBD, and 48-93% and 83-93% for detecting active disease during follow-up, respectively.

Conclusions: The diagnostic accuracy of US in detecting intestinal inflammation as seen on MRE and/or ileo-colonoscopy in paediatric IBD patients remains inconclusive, and there is currently no consensus on defining an US result as abnormal. Prospective studies with adequate sample size and methodology are needed before US can be used in the diagnostics and monitoring of paediatric IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ecco-jcc/jjz085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142400PMC
December 2019

Disease progression in paediatric- and adult-onset sclerosing cholangitis: Results from two independent Dutch registries.

Liver Int 2019 09 26;39(9):1768-1775. Epub 2019 Jun 26.

Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.

Background & Aims: Sclerosing cholangitis (SC) is a severe liver disease leading to destruction of bile ducts. It is believed to run a milder course in children than in adults. To test this assumption, we evaluated time-to-complication curves in two independent paediatric-onset cohorts from the same geographical area.

Methods: Short-term disease outcomes were evaluated with an online clinical registry that was filled with data on children with SC diagnosed between 2000 and 2017 and who were followed bi-annually thereafter. Long-term disease outcomes were evaluated in a paediatric-onset subcohort derived from a previously published population-based study from the Netherlands. Time-to-complication in the first cohort was defined as the time from diagnosis until portal hypertension, biliary obstructions and infections, development of malignancy, or liver transplantation, whichever came first. In the second cohort time-to-complication was defined as the time until liver transplantation or PSC-related death.

Results: Median age at diagnosis in the first cohort (n = 86) was 12.3 years. In the first 5 years post-diagnosis 23% of patients developed complications. The patients in the population-based study (n = 683) were stratified into those diagnosed before the age of 18 years ('paediatric-onset' subcohort, n = 43) and those diagnosed after the age of 18 years ('adult-onset' subcohort, n = 640). Median age at diagnosis was 14.6 and 40.2 years, respectively. Median time-to-complication in the paediatric-onset and adult-onset subcohorts was not statistically different.

Conclusion: Paediatric and adult-onset SC run a similar long-term disease course. Paediatricians who treat children with SC should monitor them closely to recognize early complications and control long-term sequelae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14159DOI Listing
September 2019

Hepatic symptoms and histology in 13 patients with a Zellweger spectrum disorder.

J Inherit Metab Dis 2019 09 30;42(5):955-965. Epub 2019 Jul 30.

Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Patients with a Zellweger spectrum disorder (ZSD) have a defect in the assembly or maintenance of peroxisomes, leading to a multisystem disease with variable outcome. Liver disease is an important feature in patients with severe and milder phenotypes and a frequent cause of death. However, the course and histology of liver disease in ZSD patients are ill-defined. We reviewed the hepatic symptoms and histological findings of 13 patients with a ZSD in which one or several liver biopsies have been performed (patient age 0.2-39 years). All patients had at least some histological liver abnormalities, ranging from minor fibrosis to cirrhosis. Five patients demonstrated significant disease progression with liver failure and early death. In others, liver-related symptoms were absent, although some still silently developed cirrhosis. Patients with peroxisomal mosaicism had a better prognosis. In addition, we show that patients are at risk to develop a hepatocellular carcinoma (HCC), as one patient developed a HCC at the age of 36 years and one patient a precancerous lesion at the age of 18 years. Thus, regular examination to detect fibrosis or cirrhosis should be included in the standard care of ZSD patients. In case of advanced fibrosis/cirrhosis expert consultation and HCC screening should be initiated. This study further delineates the spectrum and significance of liver involvement in ZSDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12132DOI Listing
September 2019

Comparison of diagnostic accuracy of screening tests ALT and ultrasound for pediatric non-alcoholic fatty liver disease.

Eur J Pediatr 2019 Jun 22;178(6):863-870. Epub 2019 Mar 22.

Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital, Meibergdreef 9, 1100 AZ, Amsterdam, The Netherlands.

Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). No direct comparison of these two modalities in children exists. We aimed to compare head-to-head the diagnostic accuracy of ALT and US and their combination for detecting NAFLD in children with obesity. Ninety-nine children with severe obesity underwent simultaneous serum-ALT and abdominal ultrasound (US steatosis score 0-3). Proton magnetic resonance spectroscopy was used as reference standard for detecting steatosis/NAFLD. ROC curve analyses were performed to determine diagnostic performance and to determine optimum screening cut-points aiming for a specificity ≥ 80%. The area under the ROC (AUROC) of ALT and US were not significantly different (0.74 and 0.70, respectively). At the optimal ALT threshold (≥40 IU/L), sensitivity was 44% and specificity was 89%. At the optimal US steatosis score (≥ 2), sensitivity was 51% and specificity was 80%. Combining ALT and US did not result in better accuracy than ALT or US alone.Conclusion: ALT and US have comparable and only moderate diagnostic accuracy for detecting hepatic steatosis in children with obesity. A stepwise screening strategy combining both methods does not improve diagnostic accuracy. What is Known: • Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). • ALT and ultrasound have mediocre accuracy in detecting steatosis in children with obesity. What is New: • In a head-to-head comparison, the difference in diagnostic accuracy of ALT and ultrasound in detecting steatosis is not significant. • A stepwise screening strategy combining both methods does not improve diagnostic accuracy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-019-03362-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511345PMC
June 2019

The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy.

J Inherit Metab Dis 2019 03 21;42(2):303-312. Epub 2019 Feb 21.

Department of Pediatric Neurology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Introduction: Currently, no therapies are available for Zellweger spectrum disorders (ZSDs), a group of genetic metabolic disorders characterised by a deficiency of functional peroxisomes. In a previous study, we showed that oral cholic acid (CA) treatment can suppress bile acid synthesis in ZSD patients and, thereby, decrease plasma levels of toxic C -bile acid intermediates, one of the biochemical abnormalities in these patients. However, no effect on clinically relevant outcome measures could be observed after 9 months of CA treatment. It was noted that, in patients with advanced liver disease, caution is needed because of possible hepatotoxicity.

Methods: An extension study of the previously conducted pretest-posttest design study was conducted including 17 patients with a ZSD. All patients received oral CA for an additional period of 12 months, encompassing a total of 21 months of treatment. Multiple clinically relevant parameters and markers for bile acid synthesis were assessed after 15 and 21 months of treatment.

Results: Bile acid synthesis was still suppressed after 21 months of CA treatment, accompanied with reduced levels of C -bile acid intermediates in plasma. These levels significantly increased again after discontinuation of CA. No significant changes were found in liver tests, liver elasticity, coagulation parameters, fat-soluble vitamin levels or body weight.

Conclusions: Although CA treatment did lead to reduced levels of toxic C -bile acid intermediates in ZSD patients without severe liver fibrosis or cirrhosis, no improvement of clinically relevant parameters was observed after 21 months of treatment. We discuss the implications for CA therapy in ZSD based on these results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jimd.12042DOI Listing
March 2019

Screening for lysosomal acid lipase deficiency: A retrospective data mining study and evaluation of screening criteria.

Atherosclerosis 2018 11 19;278:174-179. Epub 2018 Sep 19.

Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children's Hospital, the Netherlands.

Background And Aims: Lysosomal acid lipase deficiency (LAL-D) is a lysosomal storage disorder. In severe cases, it can cause life-threatening organ failure due to lipid substrates accumulation. However, mild phenotypes of this disorder are increasingly recognized. The aim of this study is to determine the number of missed LAL-D patients in a large pediatric hospital population.

Methods: In a retrospective data mining study, the medical files of children, who visited the outpatient clinic at a university hospital between 2000 and 2016, with high plasma low density lipoprotein cholesterol (LDL-C) levels, were evaluated. Previously developed LAL-D screening criteria, with lipid and alanine aminotransferase (ALT) values adjusted for children, were used to analyze which children are suspect for LAL-D. For suspicion of LAL-D, at least 3 out of 5 screening criteria had to be met. Subsequently data on presentation and follow-up were collected to determine if the clinical picture was compatible with LAL-D.

Results: We identified 2037 children with high LDL-C levels. Of those, 36 children complied with ≥3 screening criteria. Thirty-one of those had an underlying disorder other than LAL-D that explained the abnormalities and, in the 5 remaining children, ALT and lipid levels normalized spontaneously, thus excluding LAL-D.

Conclusions: This study shows that retrospective data mining is unlikely to yield a significant number of LAL-D cases in children. The screening algorithm adjusted for children seems useful and accurate in the selection of children for further testing, suggesting it can be applied prospectively, although further validation is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2018.09.023DOI Listing
November 2018
-->