Sarah Tizzard

Indications and Limitations of Bariatric Intervention in Severely Obese Children and Adolescents With and Without Nonalcoholic Steatohepatitis: ESPGHAN Hepatology Committee Position Statement

ABSTRACT Morbid obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD), which is one of the most common causes of chronic liver disease worldwide. The present best treatment for NAFLD and nonalcoholic steatohepatitis (NASH) is weight reduction through lifestyle modification. Because of frustrating inefficiency of such a therapeutic approach, bariatric surgery is increasingly performed in adolescents as an alternative option for weight reduction. Standards of care and consensus for indications are, however, scarce. We explore the indications and limitations of bariatric surgery in children with severe obesity with and without NASH and aim to provide guidance for the exceptional indications for adolescents with extreme obesity with major comorbidity that may benefit from these controversial interventions. Present evidence suggests that bariatric surgery can decrease the grade of steatosis, hepatic inflammation, and fibrosis in NASH. Uncomplicated NAFLD is not an indication for bariatric surgery. Roux-en-Y gastric bypass is considered a safe and effective option for adolescents with extreme obesity, as long as an appropriate long-term follow-up is provided. Laparoscopic adjustable gastric banding has not been approved by the Food and Drug Administration for use in adolescents and therefore should be considered investigational. Finally, sleeve gastrectomy and other types of weight loss surgery that have grown increasingly common in adults, still need to be considered investigational. Temporary devices may be increasingly being used in pediatrics; however, future studies, including a long-term risk analysis of patients who undergo surgery, are much needed to clarify the exact indications for bariatric surgery in adolescents.

Steroids in biliary atresia: Single surgeon, single centre, prospective study

BACKGROUND & AIMS The effect of adjuvant steroids in infants with biliary atresia (BA) is not clear and evidence of benefit is lacking. METHODS During the period Jan. 2000-Dec. 2011, 153 infants with isolated (CMV IgM-ve) BA underwent Kasai portoenterostomy (KPE) at<70 days. They were divided into three groups: LOW-dose steroid (from a previous randomized trial; starting prednisolone 2mg/kg/day, n=18), HIGH-dose steroid (starting prednisolone 5mg/kg/day, n=44), and NO steroid [n=72+19 placebo (from randomized trial)=91]. Outcome was assessed by early liver biochemistry, clearance of jaundice (<20 μmol/L), and actuarial native liver survival. Data are quoted as median (IQ range) and compared with non-parametric ANOVA, Chi or Log-rank tests as appropriate. p ≤ 0.05 was regarded as significant. RESULTS All three groups were comparable for age (ANOVA, p=0.31) and a surrogate marker of liver fibrosis [aspartate-aminotransferase index (APRi), ANOVA, p=0.67]. At 1 month post KPE, there was a significant reduction in bilirubin [58 (25-91) vs. 91 (52-145)μmol/L, p=0.0015], AST [118 (91-159) vs. 155 (108-193)IU/L, p=0.0015], and APRi [0.49 (0.28-0.89) vs. 0.82 (0.45-1.2), p=0.005] for HIGH vs. NO steroid. There was a significant increase in % clearance of jaundice with the use of steroids [47/91 (52%) vs. 12/18 (67%) vs. 29/44 (66%); steroids vs. no steroids, p=0.037]. There was no statistical difference in 4-year patient survival (96% vs. 94% vs. 95%) or native liver survival (4 year=46% vs. 50 vs. 57%). CONCLUSIONS The adjuvant use of prednisolone significantly improved early post-operative liver biochemistry (especially at the higher dose), and increased the proportion of infants who cleared their jaundice at 6 months post-KPE.

Humoral immunity in children with biliary atresia splenic malformation syndrome.

Our retrospective analysis could not identify a difference in the humoral immunity of children with biliary atresia and splenic malformations, although they appeared more prone to upper respiratory infections before transplant and septic complications after transplant. Approximately 10%–15% of infants with biliary atresia (BA) have splenic malformations [1]. These patients have worse long-term prognosis, which may be due to an increased incidence of infection [2]. We have investigated whether children with biliary atresia splenic malformation (BASM) syndrome have different rate of infections and whether they mount the same humoral response as those without splenic abnormalities. Retrospective data were available for 32 children with BASM (median age at presentation was 1.6 months, range 0.2–4.4 months, nine male). A vaccination history was obtained from the family doctor and a stored plasma sample, taken 4 weeks after the third or first booster DPT vaccination, was analysed for tetanus antibody concentration. The medical notes were reviewed to identify hospital admissions for infection. Control data were obtained from 55 children with BA and normal spleen. A total of 23 children with BASM had polysplenia, five had a double spleen and four were asplenic. Other features in the BASM group were situs inversus (n=14), cardiac defect (n=7), pre-duodenal portal vein (n=16), malrotation (n=17), absent inferior vena cava (n=11) and pancreatic abnormalities (n=4). The children with BASM syndrome had a significantly higher incidence of respiratory infection than control group (42 versus 21, P <0.05). This difference could not be observed when the asplenic subset was compared with remainder of the BASM cohort. There was no difference in episodes of cholangitis (27 versus 26 in the BASM and BA group, respectively), gastrointestinal infection (4 versus 5), pyrexia of unknown origin (5 versus 17), urinary tract infection (2 versus 5), septicaemia (1 versus 2), severe tonsillitis (2 versus 1) and otitis media (one in each group). The tetanus antibody levels are shown in Table 1. Twelve children (37.5%) required liver transplantation (LT) in the BASM group compared to 24 (43.3%) in the BA group (P= not significant). Of those, in the BASM group, five (15.5%) died (four due to sepsis and one from hepatic artery thrombosis post-LT), compared to three (5.5%) in the BA group (two due to end-stage liver disease and one due to multi-organ failure after LT). Outcome of corrective surgery for BA may be affected by the episodes of ascending cholangitis, caused by translocation of intestinal microorganisms through the ‘‘Roux-en-Y’’ biliary anastomosis, possibly aggravated by suboptimal local defence mechanisms such as acidity and peristalsis. Furthermore, some additional, yet unrecognised, systemic factors may also play a role [3, 4, 5]. The incidence of cholangitis was similar in the two selected groups. Those with BASM syndrome had fewer Table 1 Laboratory features at 18 months and in vitro assessment of humoral immunity. Data given as median (range)

Tips and hints for the transition: What adult hepatologists should know when accept teens with a pediatric hepatobiliary disease.

The number of children with chronic hepatobiliary disease surviving into adulthood is more and more increasing, but no established model of transition does exist in this category of patients. Here, we summarize medical problems expected at the time of their transition, and any impacts on morbidity and mortality in adulthood. Information provided would turn useful to adult hepatologists and practitioners responsible for ensuring continuity of care for young adults affected by diseases they are not usually accustomed to.

Current state and prospects in managing liver transplanted children

Pediatric liver transplantation (LTx) has revolutionized life chances and perspectives of children with liver disease. Following rapid establishment of the therapeutic concept in the early years of pediatric transplant medicine, more aspects beyond plain survival become increasingly important. In addition to improving the short to medium-term survival rates, researchers are focusing on themes such as rehabilitation, adherence and quality of life, long-term graft fibrosis and dysfunction, as well as the consequences of long-term immunosuppression. Also, more protocol biopsy data are available to evaluate increasing graft fibrosis. To manage their conditions, patients will need access to highly experienced pediatric liver transplant centers where clinical research will examine modulators of renal disease, endocrine and cardiovascular comorbidity and the development of graft fibrosis and malignancies. Assessment and evaluation of health-related quality of life and factors which influence clinical tolerance, adherence and transition from child to adult care will also be investigated. The analysis of multi-national registry data and more than 40years of experience with large patient cohorts will provide important clues to treatment and will thus get increasing attention. In the future, longitudinal assessment of the outcome for pediatric LTx patients should include more functional aspects than plain survival rates or laboratory parameters.