Liver Steatosis in Pediatric CD Patients

NCT06206616 | Recruiting

• 1 other identifier: ASAC01
• Study Type: observational
• Target: 91
• Locations: 1 country
• Sites: 2

Brief Summary

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:

1. 1.define, retrospectively, the prevalence of NAFLD in a pediatric population affected by CD and study its possible association with GFD.
2. 2.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.

Conditions

Celiac Disease in Children; Non-Alcoholic Fatty Liver Disease

Keywords

Celiac Disease; Non-Alcoholic Fatty Liver Disease; Intestinal Permeability; Inflammatory Cytokines; Children

Outcome Measures

Primary Outcomes (6)

• Historical Nonalcoholic Fatty Liver Disease Prevalence in Pediatric Celiac Disease Patients before Gluten Free Diet

  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)

  Retrospective (years 2000-2023)

• Historical Nonalcoholic Fatty Liver Disease Prevalence in Pediatric Celiac Disease Patients after Gluten Free Diet

  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)

  Retrospective (years 2000-2023)

• Historical Nonalcoholic Fatty Liver Disease Degree in Pediatric Celiac Disease Patients before Gluten Free Diet

  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

  Retrospective (years 2000-2023)

• Historical Nonalcoholic Fatty Liver Disease Degree in Pediatric Celiac Disease Patients after Gluten Free Diet

  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

  Retrospective (years 2000-2023)

• Historical Nonalcoholic Fatty Liver Disease Prevalence Change in Pediatric Celiac Disease Patients

  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.

  Retrospective (years 2000-2023); 1 year of diet

• Historical Nonalcoholic Fatty Liver Disease Degree Change in Pediatric Celiac Disease Patients

  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.

  Retrospective (years 2000-2023); 1 year of diet

Secondary Outcomes (29)

• 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 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 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 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 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

Study Arms (1)

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.

Behavioral: Gluten-free diet

Interventions

Gluten-free diet BEHAVIORAL

Pediatric patients affected by newly diagnosed Celiac Disease (CD) according to the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria will start a gluten-free diet (GFD), as normally expected for all CD patients. The assessment of adherence to the GFD will be carried out through the monthly compilation, by the children and/or their parents, of a specifically created and validated questionnaire. Before and after the start of GFD enrolled patients will undergo an abdominal ultrasound to establish the presence and degree of hepatic steatosis.

Celiac Disease Children

Eligibility Criteria

• Age: 1 Year - 14 Years
• Sex: all
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Celiac Disease diagnosis according European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria, aged 1-14 years.

You may qualify if:

• Age \>1 and \<14 years
• Celiac Disease diagnosis according European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria

You may not qualify if:

• age \<1 and \>14 years;
• 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.

Sponsors & Collaborators

• Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello: collaborator
• University of Palermo: lead
• ARNAS Civico Di Cristina Benfratelli Hospital: collaborator

Study Sites (2)

Gastroenterological Paediatrics, Children's Hospital "G. Di Cristina"

Palermo, Palermo, 90127, Italy

RECRUITING

General Pediatrics Unit, Children's Hospital "G. Di Cristina"

Palermo, Palermo, 90127, Italy

RECRUITING

Related Publications (10)

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• Mansueto P, Spagnuolo G, Calderone S, D'Agate CC, Cosenza S, Leonardi G, Camilleri S, Pistone M, Seminara G, Alaimo C, Soresi M, Carroccio A, Garufi S. Improving the diagnostic approach to celiac disease: Experience from a regional network. Dig Liver Dis. 2022 Jun;54(6):771-775. doi: 10.1016/j.dld.2021.11.016. Epub 2021 Dec 21.

  PMID: 34952810 BACKGROUND

• Al-Toma A, Volta U, Auricchio R, Castillejo G, Sanders DS, Cellier C, Mulder CJ, Lundin KEA. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J. 2019 Jun;7(5):583-613. doi: 10.1177/2050640619844125. Epub 2019 Apr 13.

  PMID: 31210940 BACKGROUND

• Yoosuf S, Singh P, Khaitan A, Strand TA, Ahuja V, Makharia GK. Prevalence of Celiac Disease in Patients With Liver Diseases: A Systematic Review and Meta-Analyses. Am J Gastroenterol. 2023 May 1;118(5):820-832. doi: 10.14309/ajg.0000000000002123. Epub 2022 Dec 23.

  PMID: 36599134 BACKGROUND

• Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Dec 1;78(6):1966-1986. doi: 10.1097/HEP.0000000000000520. Epub 2023 Jun 24.

  PMID: 37363821 BACKGROUND

• Yodoshi T, Orkin S, Arce-Clachar AC, Bramlage K, Xanthakos SA, Valentino PL, Mouzaki M. Alternative Etiologies of Liver Disease in Children With Suspected NAFLD. Pediatrics. 2021 Apr;147(4):e2020009829. doi: 10.1542/peds.2020-009829.

  PMID: 33785637 BACKGROUND

• Reilly NR, Lebwohl B, Hultcrantz R, Green PH, Ludvigsson JF. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease. J Hepatol. 2015 Jun;62(6):1405-11. doi: 10.1016/j.jhep.2015.01.013. Epub 2015 Jan 21.

  PMID: 25617505 BACKGROUND

• Spadoni I, Zagato E, Bertocchi A, Paolinelli R, Hot E, Di Sabatino A, Caprioli F, Bottiglieri L, Oldani A, Viale G, Penna G, Dejana E, Rescigno M. A gut-vascular barrier controls the systemic dissemination of bacteria. Science. 2015 Nov 13;350(6262):830-4. doi: 10.1126/science.aad0135.

  PMID: 26564856 BACKGROUND

• Wang HH, Lee DK, Liu M, Portincasa P, Wang DQ. Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome. Pediatr Gastroenterol Hepatol Nutr. 2020 May;23(3):189-230. doi: 10.5223/pghn.2020.23.3.189. Epub 2020 May 8.

  PMID: 32483543 BACKGROUND

• Hrncir T, Hrncirova L, Kverka M, Hromadka R, Machova V, Trckova E, Kostovcikova K, Kralickova P, Krejsek J, Tlaskalova-Hogenova H. Gut Microbiota and NAFLD: Pathogenetic Mechanisms, Microbiota Signatures, and Therapeutic Interventions. Microorganisms. 2021 Apr 29;9(5):957. doi: 10.3390/microorganisms9050957.

  PMID: 33946843 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Celiac Disease

Interventions

Diet, Gluten-Free

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

Aurelio Seidita, MD

CONTACT

00390916802764; aurelio.seidita@unipa.it

Antonio Carroccio, MD

CONTACT

00390916802764; antonio.carroccio@unipa.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 4, 2024
• First Posted: January 16, 2024
• Study Start (Estimated): November 1, 2027
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)