Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry

Interventional radiology; Paediatric hepatology; Paediatric transplant surgeryRadiologia intervencionista; Hepatologia pediàtrica; Cirurgia de trasplantament pediàtricRadiología intervencionista; Hepatología pediátrica; Cirugía de trasplante pediátricoIntroduction Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. Methods and analysis The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. Ethics and dissemination Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences

Joint ESPGHAN/NASPGHAN Guidelines for the Management of Helicobacter pylori in Children and Adolescents ( Update 2016)

Background: Because of the changing epidemiology of Helicobacter pylori infection and low efficacy of currently recommended therapies, an update of the European Society for Paediatric Gastroenterology Hepatology and Nutrition/North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommendations for the diagnosis and management of H pylori infection in children and adolescents is required. Methods: Asystematic review of the literature (time period: 2009-2014) was performed. Representatives of both societies evaluated the quality of evidence using GRADE (Grading of Recommendation Assessment, Development, and Evaluation) to formulate recommendations, which were voted upon and finalized using a Delphi process and face-to-face meeting. Results: The consensus group recommended that invasive diagnostic testing for Hpylori be performed only when treatment will be offered if tests are positive. To reach the aim of a 90% eradication rate with initial therapy, antibiotics should be tailored according to susceptibility testing. Therapy should be administered for 14 days, emphasizing strict adherence. Clarithromycin-containing regimens should be restricted to children infected with susceptible strains. When antibiotic susceptibility profiles are not known, high-dose triple therapy with proton pump inhibitor, amoxicillin, and metronidazole for 14 days or bismuth-based quadruple therapy is recommended. Success of therapy should be monitored after 4 to 8 weeks by reliable noninvasive tests. Conclusions: The primary goal of clinical investigation is to identify the cause of upper gastrointestinal symptoms rather than H pylori infection. Therefore, we recommend against a test and treat strategy. Decreasing eradication rates with previously recommended treatments call for changes to first-line therapies and broader availability of culture or molecular-based testing to tailor treatment to the individual child

Research priorities for liver glycogen storage disease:An international priority setting partnership with the James Lind Alliance

The international liver glycogen storage disease (GSD) priority setting partnership (IGSDPSP) was established to identify the top research priorities in this area. The multiphase methodology followed the principles of the James Lind Alliance (JLA) guidebook. An international scoping survey in seven languages was distributed to patients, carers, and healthcare professionals to gather uncertainties, which were consolidated into summary questions. The existing literature was reviewed to ensure that the summary questions had not yet been answered. A second survey asked responders to prioritize these summary questions. A final shortlist of 22 questions was discussed during an international multi-stakeholder workshop, and a consensus was reached on the top 11 priorities using an adapted nominal group technique.In the first survey, a total of 1388 questions were identified from 763 responders from 58 countries. These original uncertainties were refined into 72 summary questions for a second prioritization survey. In total 562 responders from 58 countries answered the second survey. From the second survey, the top 10 for patients, carers and healthcare professionals was identified and this shortlist of 22 questions was taken to the final workshop. During the final workshop, participants identified the worldwide top 11 research priorities for liver GSD. In addition, a top three research priorities per liver GSD subtype was identified.This unique priority setting partnership is the first international, multilingual priority setting partnership focusing on ultra-rare diseases. This process provides a valuable resource for researchers and funding agencies to foster interdisciplinary and transnational research projects with a clear benefit for patients

Non-invasive diagnostic tests for Helicobacter pylori infection

BACKGROUND: Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES: To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS: We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA: We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as13C or14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS: We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS: In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions

Passive immunisation as therapy for gastrointestinal infections in children

Several prophylactic studies in animals and humans have shown potential efficacy of oral therapy with non-human antibodies against different pathogens. Passive immunisation with oral antibodies against different pathogens is an attractive way to treat different gastrointestinal infections caused by pathogens such as rotavirus or enteropathogenic and enterotoxigenic Escherichia coli (EPEC; ETEC). These pathogens give rise to high morbidity and mortality from infantile diarrhoea, especially in the developing world. In addition, Helicobacter pylori, has emerged as an important pathogen for gastrointestinal disease (i.e. ulcers and gastritis). The aim was to study the efficacy of passive immunisation as therapy via the oral route. In four double-blind placebo-controlled trials, we evaluated bovine and chicken antibodies (IgY) in rotavirus and E. coli induced diarrhoea and Helicobacter pylori infection in 4-24 month old infants from Bangladesh. We also compared ELISA and immunoblotting (IB), 13 C-urea breath test (UBT) and IMS-PCR in stool for the detection of H pylori in the same population. In the diarrhoeal studies, male infants with acute watery diarrhoea were included. The children in the rotavirus trials received either 10g of hyperimmune bovine colostrum (HBC) or hyperimmune egg yolk concentrate (HEYC) per day for four days or a control preparation. Children in the E. coli study received 10g of anti-ETEC HBC and 10g of anti-EPEC HBC. Oral intake and stool losses were recorded in addition to stool frequency and clearance of pathogens from the stool. In the H. pylori trials children were screened for H. pylori with ELISA, IB, UBT, and IMSPCR in stool. H. pylori UBT-positive children received either I g/day of HBC/placebo for 30 days. Eradication of H. pylori was followed with UBT. In a separate evaluation the diagnostic methods to detect H. pylori were compared. In the HBC-rotavirus study on 80 children, there was a statistically significantly shorter duration of diarrhoea (p = 0.016), less stool output (g/kg/24h), p = 0.01, and less ORS intake (p = 0.03) in the children receiving HBC compared to placebo. The duration of rotavirus in stool was also shorter in the HBC treated group (p = 0.001). In the HEYC-rotavirus study of 85 children there was no difference in the mean duration of diarrhoea after treatment with HEYC between the groups. However, there was a statistically significant lower stool output, lesser ORS intake (p = 0.01), and lesser stool frequency (p = 0.03) on day one. Rotavirus was found less frequent in stool on day four in the HEYC treated group (p = 0.01). In the HBC-E.coli study on 63 children there were no differences between the groups regarding duration of diarrhoea, daily and total ORS intake, daily and total stool output, and stool frequency. Nor was there any difference in clearance of E. coli from the stool between the groups. In the HBC-H pylori study of 24 H. pylori infected infants, none of the children cleared the infection after one month treatment with HBC. However, measured by UBT, there seemed to be spontaneous eradication or reinfection among the children in the groups. Finally, the concordance between the three screening methods in 68 children was 62% and the prevalence adding all three methods together was 78%. Giving bovine antibodies from hyperimmunised cows, are effective as oral therapy for rotavirus diarrhoea in children, which previously has been shown for prophylactic treatment. On the other hand, the pathogenesis of E. coli may be too complex as no effect of the treatment was found. Using chicken IgY, there seems to be a beneficial potential, although further studies with higher titres are needed. It is difficult to perform clinical studies on H. pylori in high endemic areas. Better preparations containing factors directed against specific virulence factors may be effective. There is a high prevalence of H. pylori already at an early age in high endemic countries. The screening methods of H. pylori have to be validated in areas where they are used. Presently, there are no good diagnostic methods for infants

Prevalence of increased transaminases and its association with sex, age, and metabolic parameters in children and adolescents with obesity – a nationwide cross-sectional cohort study

Abstract Background Childhood obesity increases the risk of non-alcoholic fatty liver disease marked by elevated alanine aminotransferase (ALT). This study investigated the prevalence of increased ALT in children and adolescents with obesity, and its associations with sex, age, degree of obesity, and metabolic parameters. Methods Individuals between 5 and 17.99 years of age enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) before March 2020 were included. Mildly increased ALT was defined by ALT 27–51 U/L (males) and 23–43 U/L (females), while markedly increased ALT by levels above. Multiple logistic regression models were used for statistical analysis. Results Among 11,776 individuals (age 11.0 ± 3.3 years, 53.5% males), the prevalence of mildly and markedly increased ALT were 37.9 and 10.6%, respectively. A sex-age interaction was found, where increasing age strengthened the odds of markedly increased ALT in males (OR, 99% CI: 1.34, 1.29–1.4 for each year) while the corresponding pattern in females with was minuscule (1.09, 1.02–1.10). Compared to class I obesity, class II and III obesity had greater odds ratios for mildly increased ALT (class II obesity OR, 99% CI: 1.51, 1.35–1.70; class III obesity OR, 99% CI: 2.17, 1.66–2.61) and for markedly increased ALT (class II obesity OR, 99% CI: 1.82, 1.51–2.20; class III obesity OR, 99% CI 3.38, 2.71–4.23). Dyslipidemia was associated with both mildly and markedly increased ALT, all p < 0.001. Prevalence of impaired fasting glucose was 19.1% in normal ALT group, 20.4% in mildly increased ALT group, and 29.0% in markedly increased ALT group. Conclusions The risk of markedly increased ALT increased exponentially with age among boys, but not among girls. Higher degree of obesity was observed in individuals with mildly and markedly increased ALT. Further, metabolic derangements were more prevalent among individuals with mildly and markedly increased ALT