Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex.

The impact of rotavirus vaccination in the prevalence of gastroenteritis and comorbidities among children after suboptimal rotavirus vaccines implementation in Taiwan: A population-based study.

ABSTRACT: In Taiwan, rotavirus vaccination was implemented in 2006 in the private sector. The population-based impact of rotavirus vaccination on gastroenteritis and comorbidities of children remains under-investigated.We analyzed the annual prevalence of rotavirus-related disease, including gastroenteritis, convulsions, epilepsy, type I diabetes mellitus, intussusception, and biliary atresia among children under 5 years of age. Data were collected from Taiwan's National Health Insurance Research Database, a nationwide population-based database. A 16-year retrospective cohort study was conducted between 2000 and 2015.Among children <5 years of age, the prevalence of gastroenteritis decreased after 2012 (44,259.69 per 100 thousands) and remained lower through 2015 (39,931.11per 100 thousands, P < .001). The prevalence of convulsions rose steadily and significantly from 2007 (775.90 per 100 thousands) to 2015 (962.17 per 100 thousands, P < .001). The prevalence of epilepsy decreased significantly until reaching a nadir in 2013 (from 501.56 to 293.53 per 100 thousands, P < .001). The prevalence of biliary atresia tended upward, and surged suddenly in 2007 with a peak in 2013 (18.74 per 100 thousands). Among infants (<1 year of age) from 2000 to 2015, the prevalence of gastroenteritis declined steadily, and more rapidly after 2007 (22,513 to 17,285 per 100 thousands).In Taiwan, after introducing rotavirus vaccination, gastroenteritis in young children decreased, especially in infancy. However, gastroenteritis is still common in children, given other emerging pathogens. Our results highlight the impact of rotavirus vaccines on children's health in Taiwan and provide indications for future preventive medicine and healthcare strategies in children.

Scottish outcomes for extra hepatic biliary atresia post-rationalisation of services.

AIMS: To evaluate the outcome of Scottish children with extra hepatic biliary atresia (EHBA) since rationalisation of Kasai services to three English centres in 2002 (The 'Group A' centres). METHODS: All Scottish children with EHBA diagnosed between 2002 and 2009 were identified via the Scottish Society of Paediatric Gastroenterology, Hepatology and Nutrition (SSPGHAN) clinicians. A case-note review was conducted with demographics, presentation and outcome data recorded. These data were compared with historical Scottish data and data published previously by the supraregional liver units. RESULTS: 25 patients were identified, of whom 22 were referred for Kasai in the group A centres, and of whom 19 had a Kasai. 2 year transplant-free survival (TFS) was significantly lower in the SSPGHAN 2002-2009 group than the group A centres in (1) (6/18 (33%) vs 36/57 (63%), p=0.023). CONCLUSIONS: These postrationalisation data are disappointing. The emphasis for care will now focus on improved communication between, primary care, general paediatricians and surgical centres through regional and national managed clinical networks, aiming to improve future outcomes for Scottish children with BA.

Decreasing rate of biliary atresia in Taiwan: a survey, 2004-2009.

OBJECTIVES: The pathogenesis of biliary atresia (BA) is unclear, but epidemiological studies may help to elucidate possible causes. The goals of this study were to identify BA incidence changes in Taiwan in 2004-2009 and to survey the factors that might influence incidence changes to elucidate the possible causes of BA. METHODS: A Taiwan national registry system for BA has been established since 2004. By using data from the national registry system for BA, we identified BA incidence changes in 2004-2009. We also evaluated the correlations between BA incidences and estimated rotavirus vaccine coverage rates and between BA incidences and the gross domestic product. RESULTS: A total of 185 patients with BA were identified in 2004-2009 in Taiwan, whereas the number of live births was 1 221 189. Compared with the incidence of BA in 2004-2006 (1.79 cases per 10,000 live births), the incidence of BA in 2007-2009 (1.23 cases per 10,000 live births) was decreased significantly (P = .01). BA incidences were negatively correlated with the gross domestic product (P = .02) and marginally negatively correlated with rotavirus vaccine coverage rates (P = .07). CONCLUSIONS: A significant decrease in BA incidence in Taiwan since 2007 has been noted and may be related to improvements in the general socioeconomic status and the popularity of rotavirus vaccination. Although more evidence is needed to establish a direct correlation, this phenomenon may shed light on possible causes of and preventive interventions for BA.

[Liver transplantation in children]. / La transplantation hépatique chez l'enfant.

The need for paediatric liver transplantation, which in most paediatric series is the remedy for biliary atresia after Kasai's operation has failed, is not sufficiently covered by organ retrieval at the present time. In most cases, survival after liver transplantation in children is approximately 80%. Mortality is still high due to intra-operative complications in most cases. Morbidity is related to vascular complications as well as to different types of infections which occur in nearly all the children. After the initial period, growth in most children returns to normal with normal physical and intellectual development. There remain a number of questions concerning the future of liver transplantation in children. What are the limits for proper indications and contraindications? What is the risk of life-long immunosuppressive treatment? Are there alternative modalities of treatment other orthotopic liver transplantation? It must be admitted that before progress has provided answers to these questions and a better understanding of the aetiology of many congenital or metabolic diseases in children as well as a better means of treatment or prevention, that the need for liver grafts in children will continue to rise as a consequence of its own success. One point must be emphasized, since we are concerned with very young children, care should always be given by specially trained health care providers.