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There are limited data on ethical issues related to the daily practice of members of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). The role of the ESPGHAN Ethics Committee (EC) is to provide advice on such matters to its members. The present survey aimed to evaluate the current function, and reasons that ESPGHAN members consulted the ECs. One hundred and five participants from 24 different countries answered the questionnaire. Thirty-five point seven percent of the participants used the ESGHAN EC to ask about clinical practice problems and patient-related issues whereas 21.4% ask about human research questions. An important additional finding was that 66.3% of respondents consulted their hospital's EC when they had ethical concerns and 17.4% consulted with other colleagues with expertise. This is the first survey in the ESPGHAN and Europe that analyses ethical issues that are important to members of the National Societies for Pediatric Gastroenterology Hepatology and Nutrition.

Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.

The expression of hepatitis B and C virus infections in children differs from that in adults and requires specific paediatric expertise. The European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has been a pioneer in this field, having stressed the need for straightforward recommendations since the mid-1980s. Following much observation, surveillance, and research, a panel of ESPGHAN experts was able to develop such recommendations on hepatitis B infection in children in 2009, which was then followed in June 2013 by proper guidelines. In the field of Chronic Hepatitis C, in 2011 ESPGHAN experts published also the Guidance for Clinical Trials for Children and Adolescents, and approved in 2012 the NASPGHAN guidelines for treatment. The ESPGHAN Society is to be commended for its pioneering work in furthering our understanding of chronic hepatitis B and C disease presentations in infants, children, and adolescents.

OBJECTIVES: To investigate the virological outcome of chronic hepatitis B (CH-B) in children who received interferon alpha (IFN) compared with no treatment. METHODS: Seventy-four children with CH-B (median age, 6.1 years; 44 boys) selected from a cohort of 158 cases were included and divided into two groups: IFN-treated (n = 37) and control (n = 37). The controls were matched with the treated children by baseline alanine aminotransferase (ALT) levels, sex and age. The Kaplan-Meier method was performed to estimate the time to clearance of hepatitis B e antigen (HbeAg) and hepatitis B surface antigen (HbsAg). RESULTS: Mean duration of follow-up was comparable in two groups (5.2 +/- 3.8 years in treatment group versus 5.2 +/- 3.7 years in control group, NS). HBeAg and HBsAg loss occurred in 20 (54.1%) and three treated children versus 13 (35.1%) and one untreated children (NS), respectively. The 7-year cumulative HBeAg and HBsAg clearance rates were 47.5% and 8.9% after the first visit in the treatment group versus 33.5% and 4.0% in untreated children (NS), respectively. Elevated baseline ALT (two times upper limit of normal) had a significant effect on the long-term cumulative rate of HBeAg seroconversion in treated patients (P = 0.01) but not in the untreated group. CONCLUSIONS: These findings show that the overall long-term virological outcome does not differ significantly between IFN-treated and untreated children but that a significant benefit of treatment on the long term rate of HBeAg seroconversion is obtained in children with higher baseline ALT levels.

The first attempt to transplant a liver in a human was reported in 1963 (1). This 3-year-old child with biliary atresia died during the procedure because of extensive blood loss. Four years later, the first truly successful liver transplantation was accomplished, on a 11⁄2-year-old with hepatocellular carcinoma, with survival exceeding 1 year after surgery. After early attempts at transplantation in the early 1970s, the advent of cyclosporine immunosuppression and advances in surgical techniques led to the development of many clinical programs of liver transplantation being started in the United States and Europe in the early 1980s.

BACKGROUND: Belgium is a country with low endemicity for hepatitis B virus (HBV) infection. Few data are available on genotypes or serotypes of HBV among infected children. METHODS: The S region of the hepatitis B virus genome was amplified and sequenced in 23 children treated with interferon-alpha in Belgium. Nucleotide sequences were aligned and compared with other known sequences in a phylogenetic analysis. RESULTS: A high stability of the S gene was observed during treatment. Four genotypes were represented in this sample of Belgian patients (A, B, D, and E), reflecting the geographic diversity of origins. CONCLUSIONS: In this series, the wide variety of geographic origins is confirmed by the molecular characteristics of HBV. In Belgium, HBV infection of children is currently essentially an imported infection.

Using a sensitive high-performance liquid chromatography method, we quantified the concentration of polyamines (putrescine, spermidine, and spermine) in human milk as well as in a representative group of commonly used artificial infant formulas. Variations in polyamine levels were also analyzed in human milk during the immediate postnatal period. During the first week postpartum, putrescine levels in human milk remained very low and varied little, while spermidine and spermine concentrations rose markedly during the first 3 days, reaching plateau levels that were 12 and eight times higher, respectively, than the values measured on day 0. The mean total polyamine concentration was 557 +/- 18 nmol/dl with the following profile: spermine, 313 +/- 16; spermidine, 220 +/- 20; and putrescine, 24 +/- 3.5. In artificial powdered formulas, the polyamine concentration was approximately 10 times lower than in human milk, with no difference in putrescine and spermine contents between first-age and second-age formulas. By contrast, semi-elemental diets prepared by hydrolytic procedures using crude extracts of pancreatic enzymes were shown to be major sources of polyamines with a profile similar to that of human milk. Compared with first-age formulas, mean concentrations in spermine and spermidine were 39 and six times higher, respectively, in these semi-elemental diets, whereas putrescine levels remained almost equivalent in all types of milk tested. These data indicate that human milk and some semi-elemental diets provide substantial amounts of spermine and spermidine to neonates and infants that could potentially modulate intestinal maturation.

BACKGROUND: Gilbert syndrome as a rule becomes manifest in adolescence or in early adulthood; it may be transferred by the donor to orthotopic liver transplant (OLT) recipients. METHODS: We examined the frequency of Gilbert syndrome in 46 OLT pediatric recipients who had a follow-up of 1 year or more. Diagnostic criteria included unexplained chronic or recurrent unconjugated hyperbilirubinemia; its increase after reduced caloric intake plus prolonged fasting, without changes of the proportion of conjugated bilirubin; and high relative amounts of serum unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide. RESULTS: Of the 46 patients, 42 had normal bilirubin values. Only four otherwise healthy OLT recipients showed hyperbilirubinemia and normal conjugated fractions. Liver donors had been four men. Hyperbilirubinemia persisted with a fluctuating pattern for the whole follow-up after OLT in all. Total bilirubin level in blood samples obtained after reduced caloric intake and prolonged fasting became notably higher than basal values, whereas the proportion of conjugated bilirubin remained stable. High relative amounts of unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide were found. Finally, DNA from liver donors' lymphocytes was available for one jaundiced and two nonjaundiced patients: tests for abnormalities in the promoter region of the gene for the enzyme bilirubin uridine diphospho-glucuronosyltransferase were in agreement with a diagnosis of GS in the former one, CONCLUSIONS: Gilbert syndrome may have an unusual early presentation in pediatric OLT recipients.

The present report describes AIRE gene analysis in 25 children with autoimmune hepatitis type I or II. The heterozygous transversion c.961C > G (p.Ser278Arg) located in exon 7 was identified in 4 patients with autoimmune hepatitis type I, and mostly in those presenting with a positive family history for autoimmune diseases. In this subgroup of patients, the allelic frequency of this polymorphic variant was at least 3-fold higher than in healthy controls. These results suggest that heterozygous AIRE gene mutation may represent a genetic predisposition to childhood autoimmune hepatitis type I.

The aim of this article is to identify the current challenges in pediatric OLT. It is directed to all physicians who care for pediatric patients from the early prospect of liver transplant to posttransplant life. Besides assessing current information on transplant results, the coauthors of this article have identified a number of issues that they consider as the most important that need to be addressed in 2008. Some are only an update of old questions, and others are newly identified problems. The recommendations from the group are summarized at the end of each specific issue and in the consensus guidelines.