Helicobacter pylori infection found during upper endoscopy performed for the diagnosis of celiac, inflammatory bowel diseases, and eosinophilic esophagitis: A multicenter pediatric European study.

BACKGROUND: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. MATERIALS AND METHODS: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. DATA COLLECTED: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. RESULTS: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1-14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31-10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62-11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33-3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47-7.66 p 0.004]. CONCLUSIONS: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment.

Acute Hepatitis of Unknown Etiology Among Young Children: Research Agenda by the ESPGHAN Hepatology Committee.

In April 2022, an increased incidence of acute hepatitis cases of unknown etiology among previously healthy children across the United Kingdom was described. Since, more than 270 cases from the United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than 6 years of age. The clinical presentation was nonspecific with diarrhea and vomiting usually preceding the appearance of jaundice, abdominal pain, nausea, and malaise. Approximately 5% have required liver transplantation. An infectious etiology has been considered likely given the epidemiological and clinical features of the reported cases. Between 50 and 60% of the children tested were diagnosed with adenovirus infection although a clear etiological connection has still to be demonstrated. No link with SARS-CoV-2 infection and COVID-19 vaccine was found. What is not clear to date is whether the high number of acute hepatitis cases reported is related to a true increase in incidence or heightened awareness following on from the initial reports from the United Kingdom. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed a paper on the current outbreak of acute hepatitis of unknown etiology recognizing its importance and the need of approaching the current situation with a scientifically rigorous approach. The aims of the article are to summarize the current knowledge and to identify the most pertinent issues regarding the diagnosis and management of this condition and the research questions raised.

Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies.

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.

Screening for coeliac disease in preschool Greek children: the feasibility study of a community-based project.

AIM: Evaluation of the prevalence of coeliac disease (CD) in Greek paediatric population. METHODS: The project consists of two parts: (i) a pilot study of preschool children aged 2-6 years to test the feasibility and diagnostic accuracy of community-based screening and (ii) a CD prevalence study, by random clustered sampling and proportionate stratification of various geographical areas in Greece. Trained nonmedical staff performed a rapid immunochromatographic test to detect IgA antibodies to tTG-IgA and IgA deficiency. Toddlers with positive results were referred to a paediatric gastroenterologist for further assessment with serum anti-tTG IgA and EMA-IgA. Children with positive serum anti-tTG and anti-EMA underwent upper gastrointestinal tract endoscopy and small bowel biopsy and were subsequently in gluten-free diet. RESULTS: In this project participated 1136 toddlers, who were tested at school. The prevalence of positive rapid anti-tTG screening was 1:154, of IgA deficiency 1:120 and of biopsy-proven CD 1:154. The prevalence of CD from this pilot study served as expected prevalence value for sample size calculation for the main prevalence study. CONCLUSION: This protocol using rapid immunochromatographic test for the detection of both IgA deficiency and CD is easy to be performed by nonmedical staff in a community setting, enabling the accurate identification of new CD cases among asymptomatic population.

Autoimmune hepatitis type-2 and Epstein-Barr virus infection in a toddler: art of facts or an artifact?

Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) with prolonged cholestasis, elevated serum transaminases, EBV serology compatible with recent EBV infection and positive anti liver kidney microsomal antibody type 1 which is characteristic of new-onset autoimmune hepatitis type 2. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation with predominant T-lymphocytes and plasma cells and interface hepatitis. Persistent EBV-related hepatitis was excluded by the absence of viral inclusions and steatosis on liver specimens and negative liver EBV-PCR. In conclusion, our case strongly suggests that in children with prolonged cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, liver biopsy seems mandatory in an attempt to achieve a correct and timely diagnosis of a potentially catastrophic disease as autoimmune hepatitis. Although some cases of autoimmune hepatitis type 1 following EBV infection have been reported in adults, to the best of our knowledge, the present case of autoimmune hepatitis type 2 after EBV infection represents the first case in children ever reported in the English literature.

New-onset autoimmune hepatitis in young patients with preexisting liver disease.

Autoimmune hepatitis (AIH) is thought to be a primary liver disease, occurring in the absence of any known etiology. We present three unusual cases of new-onset AIH in young female patients with longstanding preexisting liver disease (Alagille's syndrome, cystic fibrosis liver disease and sickle cell hepatopathy). All patients developed an insidious onset of abdominal pain, fatigue, jaundice and hepatitis after many years of their primary diagnosis and had negative serology for hepatitis A, B, C, cytomegalovirus and Epstein-Barr virus. The occurrence of AIH in these patients may be due to a complex interaction between the underlying liver disease, chronic medication use and genetic predisposition resulting in altered immunoregulatory mechanisms.

Hepatitis C treatment concomitant to chemotherapy as "salvage" therapy in children with hematologic malignancies.

In patients with malignancies, chronic hepatitis C reactivation or severe flare is uncommon and antiviral treatment is deferred mainly due to underlying bone marrow and immune suppression. We report the use of antiviral treatment concomitantly to chemotherapy in 3 children with hematologic malignancies, chronic hepatitis C, and significant liver dysfunction.

Inflammatory bowel disease in children: the role of a positive family history.

OBJECTIVES: The aim of this study was to evaluate any potential influence of a family history of inflammatory bowel disease (IBD) on the clinical phenotypes and the course of IBD in children. METHODS: In this retrospective study, the notes of 411 children with the diagnosis of IBD, 244 (59.4%) with ulcerative colitis, 129 (31.4%) with Crohn's disease and 38 (9.2%) with IBD unclassified, who were admitted to our department between 1 January 1981 and 31 December 2007 were reviewed. The aim was to assess the prevalence of familial IBD and its impact on the age of disease onset, clinical phenotypes according to the Montreal classification, course and outcome of disease. The control group consisted of IBD children without a family history of IBD, who were admitted to the hospital during the same time period. RESULTS: Thirty five (8.5%) children had a family history of IBD, (ulcerative colitis 6.6%, Crohn's disease 10.9% and IBD unclassified 13.2%). Sixty-eight percent of the 22 pairs of first-degree relatives were concordant for the clinical phenotype of disease. Significantly, more children with familial IBD had symptom onset and/or disease diagnosis before 5 years of age compared with sporadic IBD (P = 0.01 and P = 0.014, respectively); however, no differences were seen in sex, clinical phenotypes, need for aggressive treatment and/or surgery. CONCLUSION: Children with familial IBD had earlier onset of disease compared with those with sporadic IBD. However, this had no significant impact on the clinical phenotypes, the course and/or the outcome of disease.

Percutaneous liver biopsy in hemophiliac children with chronic hepatitis C virus infection.

OBJECTIVE: To develop a protocol for safe performance of percutaneous liver biopsies in children with deficiency of factor VIII (n = 12) or IX (n = 2) and chronic hepatitis C virus infection. PATIENTS AND METHODS: Liver biopsies were performed after administration of factor VIII or IX, before and 24 weeks after cessation of antiviral therapy. To define the optimal means of providing replacement therapy, 10 children were enrolled in a randomized crossover design study of bolus versus continuous factor VIII for performance of the liver biopsy. For the crossover study, all of the patients were given a loading dose of 50 +/- 5 IU recombinant factor (rF)VIII/kg; a minimum of factor VIII activity of > or = 80% 30 to 60 minutes following factor VIII infusion was required for liver biopsy. For the bolus protocol, rFVIII 25 to 50 IU/kg was given 6, 14, 24, 36, 48, and 60 hours after completion of the loading dose. For the continuous protocol, rFVIII was given 3 to 4 IU/kg per hour for 48 hours, followed by a bolus of 25 IU/kg at 60 hours. In patients with factor IX deficiency, a loading dose of 100 IU/kg was followed by a bolus of 50 IU/kg at 3, 15, 27, and 48 hours after the loading dose. RESULTS: Twenty liver biopsies were performed in children with factor VIII deficiency without major complications. One of the 3 biopsies in the patients with factor IX deficiency was complicated by a hemoperitoneum. Midazolam and fentanyl were used in the first 8 patients. However, postbiopsy pain, presumably secondary to hematoma in 2 patients and hemoperitoneum in 1, prompted us to use ultrasound to locate a suitable biopsy site and to change to propofol; this allowed us to better immobilize the liver, to minimize postbiopsy bleeding. The subsequent 15 biopsies were well tolerated without postbiopsy pain or other complication. CONCLUSIONS: Percutaneous liver biopsy in children with factor VIII deficiency can be safely performed using either bolus or continuous infusion of recombinant factor VIII. A brief general anesthetic and ultrasound guidance are recommended.