Search

Objectives: This Multi Centre study is performed in order to evaluate foreign language acquisition at school in cochlear implant patients in the German speaking part of Switzerland. Material and Methods: In October 2016, 125 CI patients (10-18 years) were registered in the na-tional CI Database. CI non-users and mentally retarded patients were excluded. Additional data (type of schooling, foreign language learning and bilingualism) were obtained with questionnaires. German-speaking children with foreign language tuition (English and/or French) in mainstream were enrolled for further testing (n=31). The normal-hearing control group consisted of matched-pairs. Results: Hundred returned questionnaires were available for analysis. Forty-eight were in main-stream and 52% attained special schools. 88% of CI users attended foreign language tuition. The 12 CI users without foreign language learning were all enrolled in special schools. CI users with foreign language education had better German speech comprehension (89% vs. 51%; p < 0.05). Thirtyone patients were further tested. The 10 students in 6th grade had all reached the school norms in English reading and listening. For French, 3 out of 7 CI students (44%) reached the school norm for French reading and one (14%) in French listening. The normal hearing group had higher scores (83.6 vs. 76.4%) which was statistical significant for English reading. Those with bi-modal fitting also had higher test-scores (on average 84% vs. 71%; p<0.05). Conclusion: Almost 90% of our CI children attain foreign language tuition. Those without foreign language learning were all in special schools. Overall, most of the tested patients reached the cur-rent school norm for English reading and listening, whereas the French school norms appeared to be more difficult to reach. A trend for better test scores was found in the normal hearing group. Also CI users with bimodal fitting seem to perform better than bilateral implantation. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the outcomes and effectiveness of various treatment strategies in patients with hepatic artery stenosis (HAS) after pediatric liver transplantation (pLT)., Methods: This is a single center observational cohort study between January 1st, 2004 and August 1st, 2023, including pLT recipients aged <18 years. The primary outcome was graft and patient survival. The secondary outcomes included incidence of biliary complications, technical success of surgery or endovascular therapy (EVT), and changes in liver function. The cut-off for early and late HAS was 14 days after pLT., Results: Among a total of 327 pLT patients, 4 % (n = 13) developed HAS (n = 3 early; n = 10 late). Treatments included surgical revascularization for one early HAS, conservative management with anticoagulation for one early and four late HAS, and EVT for one early and six late HAS. Over a median follow-up of 28.2 months after the diagnosis of HAS, graft survival was 100 % and 83 % in early and late HAS groups, and patient survival reached 100 % in both groups. One graft loss occurred in the conservative group. Conversely, graft survival in the EVT group was 100 %., Conclusion: The long-term outcomes of HAS after pLT are excellent. Both EVT and conservative management exhibited high graft survival rates for late HAS, with EVT achieving high technical success., Competing Interests: Conflict of interest All authors declare no conflicts of interest or industry support of the article entitled: ‘Hepatic artery stenosis after pediatric liver transplantation: the potential role of conservative management’., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood., Methods: We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT., Results: In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently ( P = 0.027)., Conclusions: At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

There is increasing global concern of severe acute hepatitis of unknown etiology in young children. In early 2022, our center for liver transplantation in the Netherlands treated five children who presented in short succession with indeterminate acute liver failure. Four children underwent liver transplantation, one spontaneously recovered. Here we delineate the clinical course and comprehensive diagnostic workup of these patients. Three of five patients showed a gradual decline of liver synthetic function and had mild neurological symptoms. Their clinical and histological findings were consistent with hepatitis. These three patients all had a past SARS-CoV-2 infection and two of them were positive for adenovirus DNA. The other two patients presented with advanced liver failure and encephalopathy and underwent dialysis as a bridge to transplantation. One of these children spontaneously recovered. We discuss this cluster of patients in the context of the currently elevated incidence of severe acute hepatitis in children., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

To determine prospectively gross and fine motor development of children <2 years of age, who undergo LTX. In this prospective study, children aged <2 years who undergo LTX were tested using the motor scale of the Bayley Scales of infant and toddler development, 3rd edition Dutch version. Testing was done during screening pre- and post-LTX: at the time of hospital discharge (2-6 weeks), at 3 months, 6 months, and 1 year. Z-scores were calculated. Twenty-nine children participated in this study, 14 boys, median age 6 months, at screening for LTX. Gross motor skills were delayed pre-LTX (Z-score -1.3). Fine motor skills were normal (Z-score 0.3). Immediately post-LTX, both skills reduced, and at 1 year post-LTX, gross motor skills Z-score was -1.0 and fine motor skills Z-score 0.0. Both gross and fine motor skills Z-scores decline post-LTX and tend to recover after 1 year, gross motor skills to low normal and fine motor skills to normal levels. Monitoring of gross motor development and attention on stimulating gross motor development post-LTX remains important, to enable participation in physical activity and sport for health benefits later in life., (© 2020 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background:  Pro- and anticoagulant drugs are commonly used in pediatric liver transplantation to prevent and treat thrombotic and bleeding complications. However, the combination of baseline hemostatic changes in children with liver disease and additional changes induced by transplantation makes this very challenging. This study aimed to analyze the efficacy of clinically available pro- and anticoagulant drugs in plasma from children undergoing liver transplantation., Methods:  In vitro effects of pro- and anticoagulant drugs on thrombin generation capacity were tested in plasma samples of 20 children (≤ 16 years) with end-stage liver disease undergoing liver transplantation, and compared with 30 age-matched healthy controls., Results:  Addition of pooled normal plasma had no effect in patients or controls, while 4-factor prothrombin complex concentrate increased thrombin generation in both patients and controls, with enhanced activity in patients. At start of transplantation, dabigatran and unfractionated heparin had a higher anticoagulant potency in patients, whereas 30 days after transplantation low molecular weight heparin was slightly less effective in patients. Effects of rivaroxaban were comparable between patients and controls., Conclusion:  This study revealed important differences in efficacy of commonly used pro- and anticoagulant drugs in children with end-stage liver disease undergoing liver transplantation. Therefore, dose adjustments of these drugs may be required. The results of this study may be helpful in the development of urgently needed protocols for strategies to prevent and treat bleeding and thrombotic complications in pediatric liver transplantation., Competing Interests: None declared., (Thieme. All rights reserved.)

In adults with end-stage liver disease concurrent changes in pro- and antihemostatic pathways result in a rebalanced hemostasis. Children though, have a developing hemostatic system, different disease etiologies, and increased risk of thrombosis. This study aimed to assess the hemostatic state of children during and after liver transplantation. Serial blood samples were obtained from 20 children (≤16 years) undergoing primary liver transplantation (September 2017-October 2018). Routine hemostasis tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic proteins were measured. Reference values were established using an age-matched control group of 30 children. Thrombocytopenia was present in study patients. Von Willebrand factors were doubled and ADAMTS13 levels decreased during and after transplantation up until day 30, when platelet count had normalized. Whereas prothrombin time and activated partial thromboplastin time were prolonged during transplantation, thrombin generation was within normal ranges, except during perioperative heparin administration. Fibrinogen, factor VIII levels, and clot lysis time were elevated up until day 30. In conclusion, children with end-stage liver disease are in tight hemostatic balance. During transplantation a temporary heparin-dependent hypocoagulable state is present, which rapidly converts to a hemostatic balance with distinct hypercoagulable features that persist until at least day 30. This hypercoagulable state may contribute to the risk of posttransplant thrombosis., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background:  Hepatic artery thrombosis (HAT) and portal vein thrombosis (PVT) are serious causes of morbidity and mortality after pediatric liver transplantation. To reduce thrombotic complications, routine antithrombotic therapy consisting of 1 week heparin followed by 3 months acetylsalicylic acid, was implemented in our pediatric liver transplant program in 2003. This study aimed to evaluate incidences of bleeding and thrombotic complications since the implementation of routine antithrombotic therapy and to identify risk factors for these complications., Methods:  This retrospective cohort study includes 200 consecutive pediatric primary liver transplantations performed between 2003 and 2016. Uni- and multivariate logistic regression analysis, Kaplan-Meier method, and Cox regression analysis were used to evaluate recipient outcome., Results:  HAT occurred in 15 (7.5%), PVT in 4 (2.0%), and venous outflow tract thrombosis in 2 (1.0%) recipients. Intraoperative vascular interventions (odds ratio [OR] 14.45 [95% confidence interval [CI] 3.75-55.67]), low recipient age (OR 0.81 [0.69-0.95]), and donor age (OR 0.96 [0.93-0.99]) were associated with posttransplant thrombosis. Clinically relevant bleeding occurred in 37%. Risk factors were high recipient age (OR 1.08 [1.02-1.15]), high Child-Pugh scores (OR 1.14 [1.02-1.28]), and intraoperative blood loss in mL/kg (OR 1.003 [1.001-1.006]). Both posttransplant thrombotic (hazard ratio [HR] 3.38 [1.36-8.45]; p  = 0.009) and bleeding complications (HR 2.50 [1.19-5.24]; p  = 0.015) significantly increased mortality., Conclusion:  In 200 consecutive pediatric liver transplant recipients receiving routine postoperative antithrombotic therapy, we report low incidences of posttransplant vascular complications. Posttransplant antithrombotic therapy seems to be a valuable strategy in pediatric liver transplantation. Identified risk factors for bleeding and thrombotic complications might facilitate a more personalized approach in antithrombotic therapy., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: Treatment targets in inflammatory bowel disease (IBD) move away from controlling symptoms towards complete recovery of the intestinal mucosa. Currently, the most frequently used noninvasive surrogate marker of mucosal healing is a faecal calprotectin concentration in the target range. This study tested if there was a relation between time-to-reach target calprotectin and first flare., Methods: We prospectively included new-onset IBD patients ages 17 and younger in a cloud-based registry (FastForwardCare) and followed them for at least 52 weeks. They were treated according to Dutch national guidelines that advocate a step-up approach. Time-to-reach target was defined as the first calprotectin measurement below 250 μg/g after the start of induction therapy. Time-to-first flare was the time from the first calprotectin measurement below 250 μg/g until reappearance of symptoms with calprotectin values above 250 μg/g., Results: We included 76 patients (luminal Crohn disease [CD] 43); ulcerative colitis [UC] 33). Median age at diagnosis was, respectively 14.5 and 14.1 years. Median time-to-reach target calprotectin was 37 weeks in CD and 11 weeks in UC patients (Log-rank test, P = 0.001). Once the calprotectin target was reached, time-to-first flare was significantly longer in CD than in UC patients (Log-rank test, P = 0.001). CD patients with time-to-reach target calprotectin ≤12 weeks after conventional induction therapy (ie, exclusive enteral nutrition or steroids) had a more favorable disease course in the first year than those with time-to-reach target calprotectin >12 weeks (Log-rank test, P = 0.057). In UC patients, time-to-reach target calprotectin ≤12 weeks is not associated with a favorable disease course in the first year., Conclusions: The findings of this prospective registry suggest that a quick response to conventional therapy predicts a favorable disease course in new-onset paediatric CD, but not in UC. The concept "time-to-reach target calprotectin level" rationalizes the indefinite term "response to treatment" and is well suited for studying treatment effectiveness in real-world practices.

To determine physical activity (PA), aerobic fitness, muscle strength, health-related quality of life (HRQOL), fatigue, and participation in children after liver transplantation. Children, 6-12 years, at least one year after liver transplantation, participated in this cross-sectional study. Measurements: Time spent in moderate to vigorous PA (MVPA) was measured using an accelerometer, and aerobic fitness (VO 2 peak ) was measured by cardiopulmonary exercise testing. Muscle strength was measured by hand-held dynamometry. Fatigue was measured using the multidimensional fatigue scale, and HRQOL with the Pediatric Quality of life Core scales and leisure activities was measured using the Children's Assessment of Participation and Enjoyment. Outcomes (medians and interquartile range (IQR)) were compared to norm values. Twenty-six children participated in this study (14 boys, age 9.7 years, IQR 7.7;11.4). Children spent 0.8 hours/d (IQR 0.6;1.1) on MVPA. One child met the recommendation of at least 1 hour of MVPA every day of the week. Aerobic fitness was similar to norms (VO 2 peak 1.4  L /min , IQR 1.1;1.7, Z-score -0.3). Z-scores of muscle strength ranged between -1.4 and -0.4 and HRQOL and fatigue between -2.3 and -0.4. Participation was similar to published norms (Z-scores between -0.6 and 0.6). Young children after liver transplantation have similar MVPA patterns and aerobic fitness compared to published norms. Despite lower HRQOL, more fatigue, and less muscle strength, these children have similar participation in daily activities. Although children do well, it remains important to stimulate PA in children after liver transplantation in the context of long-term management., (© 2019 The Authors. Pediatric Transplantation Published by Wiley Periodicals, Inc.)

Introduction:  Portal hypertension often occurs in biliary atresia (BA). The subsequent development of esophageal varices and bleeding from these varices are a well-known complication. We aim to describe the incidence and severity of variceal bleeding in patients with BA. In addition, we describe the characteristics of patients who experienced variceal bleeds., Materials and Methods:  We included all infants treated for BA at our center between March 1987 and August 2015. Variceal bleeding was defined as hematemesis and/or melena with presence of varices at endoscopy. Findings at endoscopy and ultrasound, laboratory tests, clearance of jaundice, fibrosis-grade at Kasai portoenterostomy, and several varices prediction scores were documented. Routine endoscopies were not performed., Results:  In this study, 74 patients were included. During follow-up, 18 out of 74 patients (24%) developed variceal bleeding at an age of 9 months (range, 4-111). Twelve patients were listed for liver transplantation at the time of bleeding. Patients who did not clear their jaundice developed variceal bleeds more often and earlier in life. Bleeds were treated with sclerotherapy, banding, or octreotide. Four patients did not receive treatment. No bleeding-related mortality occurred., Conclusion:  One-fourth of the children diagnosed with BA experience variceal bleeds during follow-up. Most of these children are younger than 1 year and often already listed for transplantation. Major complications did not occur after variceal bleeding., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Background & Aims: Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids., Methods: We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7., Results: In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids., Conclusions: We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In the majority of long-term survivors after PLTx, graft fibrosis has been identified. Recently, subtypes of graft fibrosis have been described based on their predominant acinar localization. We aimed to evaluate whether the development of portal, perisinusoidal, and centrilobular distribution of graft fibrosis is related to patient or transplantation-related parameters. We reviewed the histological features in protocol liver biopsies taken at 1 and 5 years after PLTx of 47 children on a tacrolimus-based immunosuppressive regimen. Fibrosis was assessed according to the LAFSc. The prevalence of portal fibrosis increased from 31% to 62%, sinusoidal from 68% to 79%, and centrilobular from 76% to 85%. The presence of portal fibrosis was associated with total bilirubin and γGT levels (each P<.02) and tended to be associated with biliary complications (P=.06). Sinusoidal fibrosis was associated with prior rejection episodes (P<.02) and centrilobular fibrosis with the presence of HLA mismatches (P=.02). In conclusion, using the LAFSc, we found a high incidence of progressive fibrosis in the 1-year and 5-year protocol biopsies after PLTx. Progression of fibrosis was observed in all acinar compartments, and each of the three locations is associated with different clinical conditions., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate foreign language acquisition at school in cochlear implant patients., Study Design: Cohort study., Setting: CI center., Patients: Forty three cochlear implants (CI) patients (10-18 yr) were evaluated. CI nonusers and patients with CI-explantation, incomplete datasets, mental retardation, or concomitant medical disorders were excluded., Intervention(s): Additional data (type of schooling, foreign language learning, and bilingualism) were obtained with questionnaires. German-speaking children with foreign tuition language (English and/or French) at school were enrolled for further testing., Main Outcome Measure(s): General patient data, auditory data, and foreign language data from both questionnaires and tests were collected and analyzed., Results: Thirty seven out of 43 questionnaires (86%) were completed. Sixteen (43%) were in mainstream education. Twenty-seven CI users (73%) have foreign language learning at school. Fifteen of these were in mainstream education (55%), others in special schooling. From 10 CI users without foreign language learning, one CI user was in mainstream education (10%) and nine patients (90%) were in special schooling. Eleven German-speaking CI users were further tested in English and six additionally in French. For reading skills, the school objectives for English were reached in 7 of 11 pupils (64%) and for French in 3 of 6 pupils (50%). For listening skills, 3 of 11 pupils (27%) reached the school norm in English and none in French., Conclusions: Almost 75% of our CI users learn foreign language(s) at school. A small majority of the tested CI users reached the current school norm for in English and French in reading skills, whereas for hearing skills most of them were not able to reach the norm.

Background: Children with intestinal failure (IF) depend on parenteral nutrition (PN). The goal in the treatment of IF is to wean children off PN through intestinal rehabilitation (IR). Although the healthcare burden of IF is enormous, to our knowledge there has been no previous cost-effectiveness analysis in pediatric IF including IR., Objective: We sought to determine the cost-effectiveness of IR in terms of costs and life-years., Design: We simulated the treatment of IF in children in a discrete-event model. Data for this model were derived from patient records, the Dutch Registry of Intestinal Failure and Transplantation, the Intestinal Transplant Registry, and the literature. The time horizon of the model was 40 y. Simulated patients were enrolled at a rate of 40 patients/mo for 10 y. Actual costs were calculated for hospital admissions, surgical interventions, endoscopies, PN, and immunosuppressive medication. We evaluated the cost-effectiveness of IR by comparing 1 scenario with IR with 1 scenario without IR. In the scenario with IR, a proportion of patients who represented those with the ability to wean off PN were assigned to IR. In the scenario without IR, all patients progressed to home PN (HPN). In both scenarios, a proportion of patients receiving HPN were eventually eligible for an intestinal transplantation., Results: IR prolonged survival; the mean number of life-years per patient was 19.4 in the scenario with IR compared with 18.2 in the scenario without IR. Average total costs per patient were €819,292 in the scenario with IR compared with €1,176,830 in the scenario without IR (equivalent to 1,129,230 US$ and 1,622,025 US$, respectively, in January 2014); costs mainly included hospital admissions and PN., Conclusions: On the basis of our simulations, we concluded that IR improved the survival of children with IF and was associated with cost savings. Therefore, we consider IR to be a cost-effective treatment for children with IF., (© 2017 American Society for Nutrition.)

Objective: To evaluate the results of the national paediatric liver transplantation programme in the University Medical Centre (UMC) Groningen in the Netherlands during the past two decades., Design: Retrospective cohort study., Method: We analysed data from paediatric patients who underwent liver transplantation at UMC Groningen in the period 1995-2016. We compared outcomes from children who had undergone a liver transplantation in the period 1995-2005 (cohort A; n = 126) and in the period 2006-2016 (cohort B; n = 169). We performed a subanalysis in cohort B between liver transplantations with deceased donor livers (n = 132) and living donor liver transplantations (LDLT; n = 37)., Results: In cohort A, almost all livers came from deceased donors (99%), whereas in cohort B, 37 LDLTs (22%) were performed. The median age of recipients was significantly higher in cohort A (4.4 vs. 2.5 years; p = 0.015). Postoperative complications were comparable for both cohorts. Re-transplantations within a year after transplantation were more often performed in cohort A than in cohort B (25% vs. 12%; p = 0.004). Following LDLT, there was 2 times (5.4%) an indication for re-transplantation. In cohort B the 5-year survival rate was better than in cohort A (83 vs. 71%; p = 0.014). In cohort B, 5-year survival was higher after LDLT than after transplantation with a deceased donor liver (95 vs. 81%; p = 0.025)., Conclusion: Outcomes after paediatric liver transplantation in the Netherlands have further improved during the past two decades. With an actuarial 5-year survival of 83% in the most recent cohort, and as high as 95% following LDLT, we can say that the UMC Groningen has a successful national paediatric liver transplant programme.

Objectives: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis., Methods: Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides)., Results: Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported., Conclusions: Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

Background & Aims: Liver disease in Alagille syndrome is highly variable. Many of the patients presenting with severe cholestasis early in life improve spontaneously; 10-20%, however, have progressive disease. It is currently not possible to predict long-term hepatic outcomes in Alagille syndrome. This international, multicentre study was aimed at identifying early life predictors of liver disease outcome., Methods: Retrospective clinical, laboratory and radiographic data from a cohort of 144 Alagille syndrome patients, whose long-term hepatic outcomes had been determined a priori based on previously published criteria, were collected., Results: Sixty-seven patients had mild and 77 had severe hepatic outcome. Univariate analysis demonstrated that cholestasis and fibrosis on biopsy, as well as the presence of xanthomata were significantly different between the groups (P < 0.05 for all). Mixed model analysis revealed that total serum bilirubin and serum cholesterol were also associated with outcome (P = 0.001 and P = 0.002, respectively). Graphical representation of the data revealed a change in total bilirubin levels between 12 and 24 months of age in the mild group. Recursive partitioning identified a threshold for total bilirubin of 3.8 mg/dl (65 mmol/L) in that age-frame that differentiated between outcomes. A multivariable logistic regression model was developed using fibrosis, xanthomata and the total bilirubin cut-off of 3.8 mg/dl (65 mmol/L), which generated an area under the ROC curve of 0.792., Conclusions: The long-term hepatic outcomes of patients with Alagille syndrome can be predicted based on serum total bilirubin between the ages of 12-24 months combined with fibrosis on liver biopsy and the presence of xanthomata on physical examination., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)