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BACKGROUND: Subarachnoid hemorrhage in children is rare. The most common cause is trauma, followed by an arteriovenous malformation, aneurysm or tumor. CASE DESCRIPTION: We describe the case of an 11-year-old girl who developed sudden headache with nausea and vomiting during athletics training. Her neurological exam was normal. With imaging and a lumbar puncture a subarachnoid hemorrhage was diagnosed, based on a ruptured saccular aneurysm of the right middle cerebral artery. Endovascular treatment was unsuccessful, after which the aneurysm was treated surgically. Postoperative recovery was uneventful. Additional tests for underlying conditions were negative. CONCLUSION: Also in a child with acute headache, nausea, and vomiting, the diagnosis of a subarachnoid hemorrhage should be considered, even if neurological examination is normal. Expeditious diagnosis and treatment are important in order to prevent rebleeding.
Subject(s)
Aneurysm , Subarachnoid Hemorrhage , Child , Female , Humans , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/etiology , Subarachnoid Hemorrhage/surgery , Headache , Nausea , VomitingABSTRACT
OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. Roughly a quarter of paediatric patients with NAFLD develop nonalcoholic steatohepatitis and fibrosis. Here, we evaluated the diagnostic accuracy of previously published noninvasive fibrosis scores to predict liver fibrosis in a large European cohort of paediatric patients with NAFLD. METHODS: The 457 patients with biopsy-proven NAFLD from 10 specialized centers were included. We assessed diagnostic accuracy for the prediction of any (F ≥ 1), moderate (F ≥ 2) or advanced (F ≥ 3) fibrosis for the AST/platelet ratio (APRI), Fibrosis 4 score (FIB-4), paediatric NAFLD fibrosis score (PNFS) and paediatric NAFLD fibrosis index (PNFI). RESULTS: Patients covered the full spectrum of fibrosis (F0: n = 103; F1: n = 230; F2: n = 78; F3: n = 44; F4: n = 2). None of the scores were able to accurately distinguish the presence of any fibrosis from no fibrosis. For the detection of moderate fibrosis, area under the receiver operating characteristic curve (AUROC) were: APRI: 0.697, FIB-4: 0.663, PNFI: 0.515, PNFS: 0.665, while for detection of advanced fibrosis AUROCs were: APRI: 0.759, FIB-4: 0.611, PNFI: 0.521, PNFS: 0.712. Fibrosis scores showed no diagnostic benefit over using ALT ≤ 50/ > 50 IU/L as a cut-off. CONCLUSIONS: Established fibrosis scores lack diagnostic accuracy to replace liver biopsy for staging of fibrosis, giving similar results as compared to using ALT alone. New diagnostic tools are needed for Noninvasive risk-stratification in paediatric NAFLD.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Child , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , Platelet Count , Aspartate Aminotransferases , Alanine Transaminase , Severity of Illness Index , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , ROC Curve , Biopsy , Liver/pathologyABSTRACT
Background & Aims: The long-term outcome of paediatric non-alcoholic fatty liver disease (NAFLD) has not been well established. Between 2008 and 2012, an unselected cohort of 133 children with severe obesity was screened for NAFLD. The aim of this study was to determine the 10-year natural history of NAFLD in this cohort. Methods: All 133 participants of the original study were approached. Proton magnetic resonance spectroscopy (1H-MRS) and the Enhanced Liver Fibrosis® (ELF) test were used to assess longitudinal changes in steatosis and fibrosis, respectively. Risk factors for disease progression were explored. Results: Fifty-one of the 133 participants (38%) from the original cohort were included. The mean follow-up time was 10.3 years (range 7-13 years), 65% were female and 92% had persistent obesity. The proportion of participants with steatosis remained unchanged (47%). Nine individuals developed steatosis and in nine individuals steatosis resolved. Predefined relevant individual changes in 1H-MRS were seen in 38% of the participants. The mean ELF test did not change significantly (8.70 ± 0.58 vs. 8.51 ± 0.71, p = 0.22). However, 16% had a relevant increase in ELF test and 6% of those with NAFLD developed advanced fibrosis at follow-up. Changes in steatosis correlated with changes in established metabolic risk factors, alanine aminotransferase, and bariatric surgery. A change in the ELF test was associated with a change in triglycerides. Conclusions: This 10-year follow-up study shows that one-third of the young adults who had childhood obesity develop steatosis and in one-third steatosis resolves. Six percent of those with NAFLD had developed advanced fibrosis at follow-up. These data underscore the importance of screening for NAFLD and monitoring for progression to advanced NAFLD in young people with obesity. Impact and implications: Childhood obesity accompanied by fat accumulation in the liver persists into young adulthood in the vast majority, and 6% develop serious liver injury. Worsening of metabolic disturbances increases the risk of liver injury.
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AIM: To evaluate the feasibility of screening for non-alcoholic fatty liver disease (NAFLD) in clinical practice and the acceptance of a screening strategy, and to identify factors that determine compliance. METHODS: A screening protocol, based on alanine aminotransferase measurement and introduced to healthcare workers of Dutch outpatient obesity clinics in 2017, was evaluated. Medical files of children who visited the largest outpatient obesity clinic between 2017 and 2020 were evaluated. Focus group discussions (FGDs) were conducted with 14 healthcare workers who had been using the screening protocol. RESULTS: Screening for NAFLD was performed in 477/571 (84%) of the children. Loss of follow-up was the major reason for inadequate screening. Follow-up was performed in 81/134 children with an abnormal screening result (61%). The FGDs indicated 13 barriers for screening, regarding guideline- and knowledge-related issues. CONCLUSION: Screening for NAFLD was performed in the vast majority of the children. However, adherence to the guideline after an abnormal initial screening result needs to be improved. This can be achieved by improving the loss of follow-up of patients' and physicians' awareness of the relevance of mildly elevated ALT levels.
Subject(s)
Non-alcoholic Fatty Liver Disease , Child , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Feasibility Studies , Obesity , Mass Screening , Patient Compliance , Alanine TransaminaseABSTRACT
Genome-wide association studies in adults have identified variants in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) and mitochondrial amidoxime reducing component 1 (MTARC1) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MTARC1, and rs738409C>G in patatin-like phospholipase domain-containing protein 3 (PNPLA3). Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T>TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7; 95% confidence interval, 0.6-0.9) and a lower grade of portal inflammation (p < 0.001). rs2642438G>A in MTARC1 was associated with a lower grade of hepatic steatosis (p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective -TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down-regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1. Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.
Subject(s)
17-Hydroxysteroid Dehydrogenases , Mitochondrial Proteins , Non-alcoholic Fatty Liver Disease , Oxidoreductases , 17-Hydroxysteroid Dehydrogenases/genetics , Child , Genome-Wide Association Study , Humans , Hydroxysteroids , Mitochondrial Proteins/genetics , Non-alcoholic Fatty Liver Disease/genetics , Oxidoreductases/genetics , OximesABSTRACT
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. METHODS: We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping. RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants. CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.
Subject(s)
Cardiovascular Diseases , Non-alcoholic Fatty Liver Disease , Adult , Cardiovascular Diseases/etiology , Child , Cross-Sectional Studies , Humans , Lipidomics , Liver/pathology , Non-alcoholic Fatty Liver Disease/pathology , TriglyceridesABSTRACT
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.
Subject(s)
Cholangitis, Sclerosing/surgery , Graft Rejection/epidemiology , Hypertension, Portal/epidemiology , Liver Transplantation , Adolescent , Age Factors , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Child , Cholangitis, Sclerosing/blood , Cholangitis, Sclerosing/epidemiology , Disease Progression , Drug Resistance , Female , Glucocorticoids/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/pathology , Graft Survival , Humans , Hypertension, Portal/physiopathology , Inflammatory Bowel Diseases/epidemiology , Internationality , Male , Recurrence , Registries , Risk Factors , Time Factors , gamma-Glutamyltransferase/bloodABSTRACT
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.
Subject(s)
Elasticity Imaging Techniques , Non-alcoholic Fatty Liver Disease , Biopsy , Child , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , ROC CurveABSTRACT
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.
Subject(s)
Cholangitis, Sclerosing/drug therapy , Ursodeoxycholic Acid/therapeutic use , Vancomycin/therapeutic use , Administration, Oral , Adolescent , Bilirubin/blood , Child , Female , Humans , Male , Propensity Score , Retrospective Studies , Serum Albumin/analysis , Treatment Outcome , Ursodeoxycholic Acid/administration & dosage , Vancomycin/administration & dosageABSTRACT
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.
Subject(s)
Intestinal Diseases/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Function Tests/methods , Parenteral Nutrition, Home/statistics & numerical data , Aspartate Aminotransferases/blood , Child , Chronic Disease , Cross-Sectional Studies , Elasticity Imaging Techniques/methods , Female , Humans , Intestinal Diseases/pathology , Intestinal Diseases/therapy , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/etiology , Male , Platelet Count , Prevalence , Risk Assessment , Risk Factors , Statistics, NonparametricABSTRACT
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.
Subject(s)
Cholangitis, Sclerosing/diagnosis , Adolescent , Bilirubin/blood , Biopsy , Child , Cholangiography , Cholangitis, Sclerosing/mortality , Cholangitis, Sclerosing/pathology , Cholangitis, Sclerosing/surgery , Disease Progression , Female , Humans , Liver Transplantation , Male , Platelet Count , Prognosis , Retrospective Studies , Risk Factors , Serum Albumin/analysis , gamma-Glutamyltransferase/bloodABSTRACT
Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC).1-3 We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.
Subject(s)
Cholangitis, Sclerosing , Colitis, Ulcerative , Colorectal Neoplasms , Inflammatory Bowel Diseases , Child , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/epidemiology , Colitis, Ulcerative/complications , Colorectal Neoplasms/epidemiology , Humans , Inflammatory Bowel Diseases/complications , Risk FactorsABSTRACT
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.
Subject(s)
Elasticity Imaging Techniques , Fatty Liver , Non-alcoholic Fatty Liver Disease , Obesity, Morbid , Adolescent , Biopsy , Child , Fatty Liver/complications , Fatty Liver/diagnostic imaging , Humans , Liver/diagnostic imaging , ROC Curve , UltrasonographyABSTRACT
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.
Subject(s)
Lipidomics , Non-alcoholic Fatty Liver Disease , Adolescent , Biomarkers/metabolism , Child , Female , Humans , Lipid Metabolism , Liver/metabolism , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/metabolism , Pilot ProjectsABSTRACT
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 <50âIU/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, (Pâ=â0.066). 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.
Subject(s)
Cholangitis, Sclerosing , Colitis, Ulcerative , Inflammatory Bowel Diseases , Adolescent , Antibodies, Monoclonal, Humanized/therapeutic use , Child , Cholangitis, Sclerosing/drug therapy , Colitis, Ulcerative/drug therapy , Female , Humans , Inflammatory Bowel Diseases/drug therapy , Male , Retrospective StudiesABSTRACT
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.
Subject(s)
Non-alcoholic Fatty Liver Disease , Adult , Child , Hospitals , Humans , Netherlands/epidemiology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Obesity , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Cholangitis, Sclerosing/mortality , Gastroenterology/methods , Models, Statistical , Pediatrics/methods , Risk Assessment/methods , Child , Cholangitis, Sclerosing/complications , Female , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/mortality , Humans , Kaplan-Meier Estimate , Liver Function Tests/methods , Male , Predictive Value of Tests , Prognosis , Reproducibility of ResultsABSTRACT
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults in industrialized countries. Besides liver-related morbidity, NAFLD is also associated with an increased risk of cardiovascular disease, type 2 diabetes and mortality at adult age. However, despite the high prevalence and serious complications, diagnosing and staging of disease remains complicated due to a lack of accurate screening tools and non-invasive methods to detect fibrosis. Areas covered: Recent insights in epidemiology, pathogenesis, diagnostic evaluation and treatment options in pediatric NAFLD are being reviewed, with a particular focus on new developments in diagnostic tools. Expert opinion: Due to their long life span, children with NAFLD are particularly at risk of complications in their lifetime. Therefore, an effective screening strategy for children to identify those with NAFLD at risk of complications is urgently needed. This is further underscored by new pharmacological therapies that are expected to become available in the next 5 years. Momentarily no accurate non-invasive method for diagnosing pediatric NAFLD is available. New promising biomarkers and imaging tools could hopefully provide better screening tools and could contribute to the development of a successful management plan to identify children with NAFLD.
Subject(s)
Biopsy/trends , Diagnostic Imaging/trends , Liver Function Tests/trends , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/therapy , Adolescent , Age of Onset , Child , Diffusion of Innovation , Female , Humans , Male , Non-alcoholic Fatty Liver Disease/epidemiology , Predictive Value of Tests , Prevalence , Risk Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Alanine Transaminase/blood , Non-alcoholic Fatty Liver Disease/diagnosis , Ultrasonography/methods , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Spectroscopy/methods , Male , Pediatric Obesity/complications , Predictive Value of Tests , ROC Curve , Severity of Illness IndexABSTRACT
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.