Sclerosing Cholangitis in Pediatric Inflammatory Bowel Disease: Early Diagnosis and Management Affect Clinical Outcome.

OBJECTIVE: To describe the characteristics and clinical course of children and young persons with inflammatory bowel disease (IBD) and sclerosing cholangitis (SC). STUDY DESIGN: Retrospective analysis of clinical characteristics, management, and outcome of two separate cohorts of children and young persons with IBD-SC managed in a tertiary pediatric gastroenterology center and in a tertiary pediatric hepatology center in the UK. RESULTS: Eighty-two pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 ± 2.8 years were followed up for a mean of 6.8 ± 3.3 years. The most common type of IBD was ulcerative colitis (55%), followed by unclassified IBD (30%) and Crohn's disease (15%). Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%. Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis. Patients in the gastroenterology center, who were diagnosed with liver disease sooner after diagnosis of IBD compared with the hepatology center cohort (mean, 2.7 ± 6.1 months vs 9.3 ± 19.4 months; P = .03), did not develop liver-related complications during follow-up. CONCLUSIONS: Our data suggest that children with IBD-SC have better clinical outcomes than have been reported previously, particularly if diagnosed early. We recommend prompt assessment for SC, including liver biopsy and biliary imaging, when liver function abnormalities are detected in a children diagnosed with IBD.

European paediatric non-alcoholic fatty liver disease registry (EU-PNAFLD): Design and rationale.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in children and has the potential to progress to advanced fibrosis/cirrhosis, end-stage liver disease and hepatocellular carcinoma. However, the natural history of the condition is poorly understood and there are no approved treatments. The European Paediatric Non-Alcoholic Fatty Liver Disease Registry (EU-PNAFLD) is a multi-centre registry of paediatric NAFLD that will serve as a prospective, observational, natural history study and provide a tractable back-bone to support recruitment into subsequent interventional trials. Collection of samples into a bio-repository will facilitate translational studies, including genome sequencing and metabolomics. EU-PNAFLD will work closely alongside the existing adult European NAFLD Registry to obtain data on clinical outcomes after 20-30 years. Through an international, well-characterised large-scale cohort, EU-PNAFLD will address the key questions in paediatric NAFLD and benefit patients with the condition.

Early Treatment Response Predicts Outcome in Paediatric Ulcerative Colitis: GASTROENTEROLOGY: INFLAMMATORY BOWEL DISEASE.

The disease course of children with ulcerative colitis (UC) varies substantially. Published data on predictors of disease outcomes in children remain scarce. We validate clinical predictors of outcomes in 93 children with UC in a single centre (age range: 2-18 years, minimum follow-up: 18 months). We stratified children into 3 groups according to their disease course, that is, 1 = mild (38/93, 40.9%), 2 = moderate (38/93, 40.9%), 3 = severe (17, 18.2%). Comparison of clinical and biochemical parameters was performed between groups using Chi-square, Mann-Whitney, and log-rank tests. Predictors of a severe disease course included pancolitis (P 0.01), low albumin (P 0.005), low haemoglobin at diagnosis (P 0.04), paediatric ulcerative colitis activity index (PUCAI) at 3 months, and nonresponse to steroids at 3 months (P 0.0001). In our cohort, failure to achieve remission at 3 months implied an 80% likelihood to require biologics or major surgery within 18 months. A specific 3-month review point is recommended to guide future management.

Auto-immune cholangiopathy in a juvenile patient with systemic lupus erythematosus.

UNLABELLED: Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease characterized by the presence of auto-antibodies. Liver enzyme abnormalities are common but clinical liver dysfunction with jaundice is rare. We report a juvenile female patient with SLE who developed jaundice 9 months after her initial presentation. Further investigations including liver biopsy and magnetic resonance cholangio-pancreatography revealed two likely pathologies for her liver dysfunction; amoxicillin-clavulanic acid induced cholestasis and auto-immune cholangiopathy. The hyperbilirubinaemia resolved spontaneously 3 months after exposure to amoxicillin-clavulanic acid; however, the elevation in Alanine transaminase and Gamma-glutamyl transpeptidase persisted until intensive immunosuppressive therapy achieved complete remission. CONCLUSION: We report a rare case of a juvenile patient with SLE and auto-immune cholangiopathy. The use of cholangio-pancreatography as part of the diagnostic work-up achieved the final diagnosis.

Laparoscopic adult colorectal surgeon and adolescents with inflammatory bowel disease: a safe combination?

INTRODUCTION: A multidisciplinary tertiary service for adolescents with inflammatory bowel disease (IBD) was commenced in April 2008, aiming to provide specialist treatment for adolescent patients and bridge the gap between existing paediatric and adult surgical services. A single laparoscopic colorectal surgeon who normally treats adult patients has been part of the multidisciplinary team since its inception. AIM: To analyse outcomes for those patients requiring surgical resection during the first 2 years of service. METHODS: In this service evaluation study, all data for patients undergoing surgery from 1 April 2008 to 31 March 2010 were prospectively collected on a dedicated electronic database. RESULTS: Nineteen patients underwent surgical resection (15 laparoscopic and four open) over the 2-year period. Median patient age was 15 years (range 11-16), and 14 patients were female. Of the 15 laparoscopic resections, eight were subtotal colectomy and ileostomy and seven ileocaecal resection/right hemicolectomy. There was one (6.7%) conversion due to a pericolic abscess. There were four planned open cases, including two subtotal colectomy and ileostomy and two small bowel resections. Median operating time was 150 and 172.5 min in the open and laparoscopic groups respectively. Median length of stay was 6 days (range 3-16) in the laparoscopic group, and 8 days (range 5-13) in the open group. There were three (15.8%) post-operative complications, one (5.3%) readmission within 30 days and no mortality. CONCLUSION: This study suggests that an adult colorectal surgeon can provide a safe and effective service for adolescents with IBD, including the provision of laparoscopic resection in this challenging patient group.

Expression of human beta-defensins in children with chronic inflammatory bowel disease.

BACKGROUND: Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children. METHODS: Intestinal biopsies were obtained from the duodenum (n = 88), terminal ileum (n = 90) and ascending colon (n = 105) of children with Crohn's disease (n = 26), ulcerative colitis (n = 11) and healthy controls (n = 16). Quantitative real-time (RT) PCR was performed and absolute mRNA copy numbers analyzed for hBD1-3 as well as inflammatory cytokines IL-8 and TNF-alpha. RESULTS: Significant induction of hBD2 and hBD3 was observed in the inflamed terminal ileum and ascending colon of IBD children. In the ascending colon induction of hBD2 was found to be significantly lower in children with Crohn's disease compared to ulcerative colitis. A strong correlation was found between inducible defensins hBD2 and 3 and the inflammatory cytokines IL-8 and TNF-alpha, both in the terminal ileum and ascending colon. CONCLUSION: Our study demonstrates distinct changes in hBD expression throughout the intestinal tract of children with IBD, lending further support for their potential role in disease pathogenesis.