The role of monocyte chemotaxis protein-1 and the ductular reaction in initiating fibrogenesis in pediatric cholestatic liver disease

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Circulating microRNAs as noninvasive diagnostic biomarkers of liver disease in children with cystic fibrosis

Objectives: Cystic fibrosis liver disease (CFLD), resulting from progressive hepatobiliary fibrosis, causes significant morbidity and mortality in up to 20% of children with cystic fibrosis (CF). Both pathogenesis and early detection of CFLD are elusive. Current diagnostic procedures to detect early CFLD and stage fibrosis severity are inadequate. Recent studies highlight a role for microRNAs (miRNAs) in the pathogenesis of many diseases and have suggested that serum miRNAs could be used as diagnostic biomarkers. Methods: We profiled circulating serum miRNA levels in patients with CFLD (n = 52), patients with CF without liver disease (CFnoLD, n = 30), and non-CF pediatric controls (n = 20). Extracted RNA was subjected to polymerase chain reaction (PCR) array of 84 miRNAs detectable in human serum. Seven candidate miRNAs identified were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), normalizing data to geNorm-determined stable reference genes, miR-19b and miR-93. Results: miR-122 was significantly elevated in patients with CFLD versus patients with CFnoLD and controls (P < 0.0001). miR-25 (P = 0.0011) and miR-21 (P = 0.0133) were elevated in patients with CFnoLD versus patients with CFLD and controls. CFLD was discriminated by both miR-122 (area under the curve [AUC] 0.71, P = 0.002) and miR-25 (AUC 0.65, P = 0.026). Logistic regression combining 3 miRNAs (-122, -25, -21) was greatly predictive of detecting CFLD (AUC 0.78, P < 0.0001). A combination of 6 miRNAs (-122, -21, -25, -210, -148a, -19a) distinguished F0 from F3–F4 fibrosis (AUC 0.73, P = 0.04), and miR-210 combined with miR-22 distinguished F0 fibrosis from any fibrosis, that is, F1–F4 (AUC 0.72, P = 0.02). Conclusions: These data provide the first evidence of changes to circulating miRNA levels in CF, suggesting that serum-based miRNA analysis may complement and extend current CFLD screening strategies with potential to predict early hepatic fibrosis.Naomi L. Cook, Tamara N. Pereira, Peter J. Lewindon, Ross W. Shepherd, and Grant A. Ram

Perspectives on transfer and transition care of adolescents with inflammatory bowel disease (IBD) from paediatric to adult care: a survey of paediatric and adult gastroenterologists in Australia and New Zealand

Background: Basic principles guiding transfer and transition of adolescents with chronic diseases from paediatric to adult care have been established. However, transfer and transition programs specific to the needs of adolescents with IBD have not yet been formulated. Aims: We aimed to identify the barriers to effective transition and explore the perceived needs of adolescents with IBD among paediatric and adult gastroenterologists in Australia and New Zealand. Methods: A web-based survey was distributed to 19 senior paediatric and adult IBD clinicians under the auspices of AIBDA. In addition to demo-graphic details, respondents were asked to rate on a scale of 1–5 (using a Likert scale which varied from 1 – strongly disagree to 5 – strongly agree) the importance of the various competencies of adolescents with IBD required for successful transition as well as the barriers to transition and ideal methods for delivery of transition care. Results: There was a 95% (18/19) response rate (50% of respondents were adult gastroenterologists and 50% were paediatric gastroenterologists). Eighty-nine percent of respondents agreed that a structured transition process was desirable for adolescents with IBD. Readiness for transfer/transition: Less than a quarter of respondents (22%) felt that adolescents with IBD were adequately prepared for their transition from paediatric to adult care. Compared to adult gastroenterologists, paediatric gastroenterologists emphasized the importance of psychological maturity (P < 0.01), growth/nutrition status (P < 0.05) and achievement of educational milestones (P < 0.05). Timing of Transfer: Completion of schooling and self-efficacy were both seen as being more important in determining the timing of transfer than chronological age or disease activity. Achievement of clinical remission and need for pelvic surgery were felt to be the most important disease factors in timing of transfer. Barriers to effective transition: Poor handover between paediatric and adult medical units was the most commonly cited barrier to effective transition. Compared to adult gastroenterologists, paediatric gastroenterologists emphasized lack of continuity in adult practice (P < 0.05), patient distance from a tertiary centre (P < 0.05) and lack of self-efficacy (P < 0.001) as barriers to effective transition. Seventy-eight percent of adult gastroenterologists felt that their training in the care of adolescents with chronic diseases and their knowledge of assessment of growth and nutritional status in adolescent patients was inadequate. Conclusion: This survey highlights a number of barriers that exist to the successful transition of adolescents with IBD from paediatric to adult care. A structured transfer and transition process including development of handover tools, and protocols for timing of transition may improve the outcomes of transition in IBD.Emily K Smith, Jane Andrews, Peter Bampton, David Moore, James Williams, Daniel Lemberg, Andrew S Day, Richard Gearry, Paul Pavli, Ravi Ravikumaran, Jarrad Wilson, Peter Lewindon, Graham Radford-Smith, Jeremy Rosenbaum, Donald Cameron, Anthony Catto-Smith, Paul Desmond, William Connell, George Alex, Sally Bell, Peter De Cru