Liver Steatosis in Pediatric Celiac Disease Patients: Exploring the Epidemiological and Pathophysiological Features of an Underestimated Condition
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 91
- 试验地点
- 4
- 主要终点
- Historical Nonalcoholic Fatty Liver Disease Degree Change in Pediatric Celiac Disease Patients
研究概览
简要总结
Celiac disease (CD) is an autoimmune enteropathy triggered by the intake of gluten, characterized by a genetic predisposition. Although, CD is often associated with malabsorption symptoms, a growing number of affected subjects are overweight or frankly obese. One of the conditions that is most frequently detected in pauci/asymptomatic subjects is an increase in transaminases, which often regresses completely after the start of GFD.
More recently, a specific liver disorder has shown a certain relevance in adult patients suffering from CD, so much so that the European Society for the Study of Coeliac Disease (ESsCD) has cited it among the possible comorbidities which should be screened in CD subjects: Non-Alcoholic Fatty Liver Disease (NAFLD).
In adults, a non-random association between CD and NAFLD has been demonstrated, showing a CD prevalence rate of 2-14% among patients with NAFLD. Few studies have focused on this same aspect in pediatric age, reporting contrasting data.
Several factors have been advocated as putative responsible of association between CD and NAFLD: dietary imbalances, intestinal mucosa permeability impairment, alterations of the intestinal microbiota.
The objectives of this study are:
- define, retrospectively, the prevalence of NAFLD in a pediatric population affected by CD and study its possible association with GFD.
- define the possible role of the intestinal permeability alteration and/or the intestinal mucosa damage and/or the proinflammatory status in the development of NAFLD in children affected by CD.
详细描述
Background Celiac disease (CD), an autoimmune enteropathy triggered by the intake of gluten, is a widespread pathology, with a worldwide estimated prevalence of approximately 1%, characterized by both gastrointestinal and systemic symptoms, both in adults and children, which are usually resolved by eliminating gluten from the diet (Gluten-Free Diet, GFD). However, it still remains an under-diagnosed condition (to date the overall prevalence in Italy is 0.37% and in Sicily 0.35%).
Although, CD is often associated with malabsorption symptoms (steatorrhea, weight loss, nutritional deficits, etc.), a growing number of affected subjects are overweight or frankly obese. One of the conditions that is most frequently detected in pauci/asymptomatic subjects is an increase in transaminases, which often regresses completely after the start of GFD.
More recently, a specific liver disorder has shown a certain relevance in patients suffering from CD, so much so that the European Society for the Study of Coeliac Disease (ESsCD) has cited it among the possible comorbidities which should be screened in CD subjects: Non-Alcoholic Fatty Liver Disease (NAFLD). This condition affects approximately 34% of overweight or frankly obese children and is closely related, both in children and adults, to the traits of metabolic syndrome, so much so that today it is preferably referred to as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). In adults, a non-random association between CD and NAFLD has been demonstrated, showing a CD prevalence of 2-14% among patients with NAFLD. Few studies have focused on this same aspect in pediatric age, however reporting that the prevalence of CD among children with NAFLD could be comparable to the prevalence of CD in the general pediatric population. Nevertheless, a study conducted on 11488 children (0-19 years) affected by CD compared with 57029 healthy children supports the hypothesis of a close association between CD and NAFLD in childhood. Authors proved a 4.6 relative risk value of NAFLD in CD patients.
Several factors have been advocated as putative responsible for this association: 1) dietary imbalances due to the adoption of GFD, rich in fats and sugars and low in fiber; 2) alteration of intestinal permeability, with an increase in the translocation of bacterial substances from the gut, which, are transported directly to the liver, where they are able to generate inflammatory processes mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), activated by the Tool-like receptor 4 (TLR4)-Lipopolysaccharide (LPS)-LPS Binding Protein (LPB) complex, with production of proinflammatory cytokines [Tumor Necrosis Factor (TNF)-α, Interleukine (IL)-1β, IL-6, IL-12, IL-18); 3) alterations of the intestinal microbiota.
Objectives
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Year 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >1 and <14 years
- •Celiac Disease diagnosis according European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria
排除标准
- •age <1 and >14 years;
- •self-exclusion of gluten/wheat from the diet and refusal to reintroduce it, for diagnostic purposes, before entering the study;
- •bacterial and/or parasitic infections;
- •diagnosis of chronic inflammatory intestinal diseases and other organic pathologies affecting the digestive system (for example, serious liver diseases), nervous system diseases, immunological deficits and impairments that limit physical activity;
- •diagnosis of cancer
- •patients undergoing chemotherapy and/or radiotherapy.
研究组 & 干预措施
Celiac Disease Children
Pediatric patients affected by newly diagnosed CD according to the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria will be evaluated before the start of gluten-free diet and after 6 months of gluten-free diet.
干预措施: Gluten-free diet (Behavioral)
结局指标
主要结局
Historical Nonalcoholic Fatty Liver Disease Degree Change in Pediatric Celiac Disease Patients
时间窗: Retrospective (years 2000-2023); 1 year of diet
A comparison between pre and post gluten free diet (1 year of diet) Nonalcoholic Fatty Liver Disease degree will be performed in all historical pediatric celiac disease patients who have undergone an abdominal ultrasound both before and after the introduction of the GFD. Hepatic steatosis will be ascertained by ultrasound examination and classified as reported in outcomes 3 and 4. Difference will be considered significant for p\<0.05.
Historical Nonalcoholic Fatty Liver Disease Prevalence in Pediatric Celiac Disease Patients after Gluten Free Diet
时间窗: Retrospective (years 2000-2023)
We will review all the clinical charts of historical Celiac Disease pediatric patients to identify the number of patients suffering from Nonalcoholic Fatty Liver Disease after the start of gluten free diet (at least 1 year of diet). Hepatic steatosis will be ascertained by ultrasound examination and classified as follows: absent (score 0), present (score 1)
Historical Nonalcoholic Fatty Liver Disease Degree in Pediatric Celiac Disease Patients after Gluten Free Diet
时间窗: Retrospective (years 2000-2023)
We will review all the clinical charts of historical Celiac Disease pediatric patients to identify the steatosis degree of patients suffering from Nonalcoholic Fatty Liver Disease after the start of gluten free diet (at least 1 year of diet). Hepatic steatosis will be ascertained by ultrasound examination and classified as follows: when the echostructure of the liver is normal; mild (score 1 = mild), when there is a mild and diffuse increase in hepatic echogenicity, with normal visualization of the portal vein wall and diaphragm; moderate (score 2 = moderate), in case of moderate increase in hepatic echogenicity, with slightly altered appearance of the portal vein wall and diaphragm; severe (score 3 = severe), in case of marked increase in hepatic echogenicity, with poor or absent visualization of the wall of the portal vein, the diaphragm and the posterior part of the right hepatic lobe
Historical Nonalcoholic Fatty Liver Disease Degree in Pediatric Celiac Disease Patients before Gluten Free Diet
时间窗: Retrospective (years 2000-2023)
We will review all the clinical charts of historical Celiac Disease pediatric patients to identify the steatosis degree of patients suffering from Nonalcoholic Fatty Liver Disease before the start of gluten free diet. Hepatic steatosis will be ascertained by ultrasound examination and classified as follows: when the echostructure of the liver is normal; mild (score 1 = mild), when there is a mild and diffuse increase in hepatic echogenicity, with normal visualization of the portal vein wall and diaphragm; moderate (score 2 = moderate), in case of moderate increase in hepatic echogenicity, with slightly altered appearance of the portal vein wall and diaphragm; severe (score 3 = severe), in case of marked increase in hepatic echogenicity, with poor or absent visualization of the wall of the portal vein, the diaphragm and the posterior part of the right hepatic lobe
Historical Nonalcoholic Fatty Liver Disease Prevalence Change in Pediatric Celiac Disease Patients
时间窗: Retrospective (years 2000-2023); 1 year of diet
A comparison between pre and post gluten free diet (1 year of diet) Nonalcoholic Fatty Liver Disease evidence will be performed in all historical pediatric celiac disease patients who have undergone an abdominal ultrasound both before and after the introduction of the GFD. Hepatic steatosis will be ascertained by ultrasound examination and classified as follows: absent (score 0), present (score 1). Difference will be considered significant for p\<0.05.
Historical Nonalcoholic Fatty Liver Disease Prevalence in Pediatric Celiac Disease Patients before Gluten Free Diet
时间窗: Retrospective (years 2000-2023)
We will review all the clinical charts of historical Celiac Disease pediatric patients to identify the number of patients suffering from Nonalcoholic Fatty Liver Disease before the start of gluten free diet. Hepatic steatosis will be ascertained by ultrasound examination and classified as follows: absent (score 0), present (score 1)
次要结局
- Historical Albuminemia changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical Aspartate Aminotransferase changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical anti-tissue transglutaminase immunoglobulin A changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical Alanine Aminotransferase changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical insulinemia changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical anti-gliadin immunoglobulin A changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical fasting glycemia changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Intestinal permeability markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: anti-claudin 1 antibodies(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Inflammatory markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: interleukin 18(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Historical total cholesterolemia changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical human leukocyte antigen status in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023))
- Intestinal permeability markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: anti-occludin antibodies(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Intestinal permeability markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: claudin 1(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Duodenal mucosa damage markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: lipopolysaccharide binding protein(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Inflammatory markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: interleukin 6(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Historical anti-gliadin immunoglobulin G changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical anti-tissue transglutaminase immunoglobulin G changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Historical Marsh duodenal histological classification changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Body Mass Index changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients.(Retrospective (years 2000-2023); 1 year of diet)
- Inflammatory markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: interleukin 12(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Historical anti-endomysial antibodies immunoglobulin A changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Duodenal eosinophils infiltration changes between pre and post gluten free diet in Nonalcoholic Fatty Liver Disease Pediatric Celiac Disease Patients(Retrospective (years 2000-2023); 1 year of diet)
- Intestinal permeability markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: zonulin(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Duodenal mucosa damage markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: Intestinal Fatty Acid Binding Protein 2(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Duodenal mucosa damage markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: lipopolysaccharide(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Intestinal permeability markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: occludin(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Inflammatory markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: tumor necrosis factor a(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
- Inflammatory markers changes in newly diagnosed Pediatric Celiac Disease Patients before and after gluten free diet: interleukin 1b(6 months [from T0 (before start of gluten-free diet) to T1 (after 6 months of gluten-free diet)])
研究者
Aurelio Seidita
Assistant Professor
University of Palermo