ABSTRACT Objectives: Besides the central role of the adaptive immune system, a disturbance of innate immunity is also involved in the pathogenesis of celiac disease (CD). Inasmuch as CD and type 1 diabetes mellitus (T1DM) frequently coexist because of a common genetic predisposition, our aim was to study the frequency of CD14 C‐260T and TLR4 A+896G single nucleotide polymorphisms (SNPs) and the distribution of HLA‐DQ genotypes in children affected by CD, T1DM, or both. Patients and Methods: TLR4 and CD14 SNPs were tested by polymerase chain reaction, followed by restriction fragment length polymorphism analysis in 80 children with T1DM, 100 children with CD, and 47 children with both CD and T1DM. Determination of HLA‐DQ alleles was done by sequence‐specific polymerase chain reaction. Frequencies were compared with those of healthy control children. Results: The prevalence of the homozygous CD14 C‐260TT genotype was significantly ( P = 0.0081) lower in children with T1DM but not in those with CD and T1DM, compared with control children. No difference was found in the genotype and allele frequencies of TLR4 between the studied groups. In patients with T1DM, the frequency of the homozygous HLA‐DQ8 genotype was significantly higher than in CD, whereas the frequency of homozygous or heterozygous HLA‐DQ2 genotypes did not differ from that in control children. In patients with CD, both homozygous and heterozygous HLA‐DQ2 genotypes were significantly more frequent than in the control and T1DM groups, and no elevation in the frequency of the HLA‐DQ8 genotypes was observed. In patients with T1DM and those with CD and T1DM, the occurrence of HLA‐DQ2/8 heterozygosity was significantly higher than in children with CD only and in control children. Conclusions: Our results suggest that in patients with T1DM, the CD14 C‐260TT homozygous genotype increases the risk for the development of CD. The distribution of HLA‐DQ genotype is different in children with CD and T1DM than in children with CD or T1DM only. Determination of the HLA‐DQ genotype in children with T1DM may help in estimating the risk for the development of CD.
Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.
Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] μmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 μmol/L (P = 0.05) tended to be associated with improved NLS. Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.
33 Efficacy of Helicobacter pylori (HP) eradication treatment is influenced by the primary resistance rate of the infecting strains. In a previous study over a 9-year period, we found 119/401 (30 %) strains resistant to at least one antibiotic before any treatment, steadily increasing in the last 4 years. Although the treatment regimen can be adapted to the results of the antibiogram, failure of eradication can be due to secondary resistance acquired during treatment. Aim: to evaluate the effect of secondary resistance on the eradication rate of HP strains in children. Methods: through 1993-97, in a series of 294 children (mean age 12.5 ± 5.3 years) with HP gastritis, 244 children were treated with several combinations of antibiotics according to the indications of an antibiogram and the efficacy of the treatment duly checked with the non invasive 13C-urea breath test. A second endoscopy with biopsies for culture and antibiogram was proposed before commencing a second treatment. Results: follow-up was not available in 24/244 (10%) children; among the 220 others 140/220 (64%) were cured and 80/220 (36%) remained infected. From these 80 children, HP strains could be isolated and cultured in 55 out of the 58 who underwent a second endoscopy. Resistance to at least one antibiotic was found in 34/55 (62%) HP strains. In 30/55 (54%) the antibiogram remained unchanged whereas in 4/55, the primary resistance was no more detected and, in 21/55 (38%), an acquired resistance against the last antibiotic used was found. Conclusions: 1) following treatment acquired secondary resistance of HP strains is a frequent mechanism that can account for failure of eradication 2) the emerging of a secondary resistance in 38% and the loss of resistance in 8% of HP strains, implies that children can probably be infected with multiple strains bearing different phenotypes.
Clinical presentations of Wilson's disease (WD) in childhood ranges from asymptomatic liver disease to cirrhosis or acute liver failure, whereas neurological and psychiatric symptoms are rare. The basic diagnostic approach includes serum ceruloplasmin and 24-hour urinary copper excretion. Final diagnosis of WD can be established using a diagnostic scoring system based on symptoms, biochemical tests assessing copper metabolism, and molecular analysis of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims at removal of copper excess by chelating agents as D-penicillamine, trientine, or inhibition of intestinal copper absorption with zinc salts. Acute liver failure often requires liver transplantation. This publication aims to provide recommendations for diagnosis, treatment, and follow-up of WD in children.Questions addressing the diagnosis, treatment, and follow-up of WD in children were formulated by a core group of ESPGHAN members. A systematic literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to 2016 was performed focusing on prospective and retrospective studies in children. Quality of evidence was assessed according to the GRADE system. Expert opinion supported recommendations where the evidence was regarded as weak. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using the nominal voting technique.
