Prevalence of Non-Alcoholic Fatty Liver Disease in Inflammatory Bowel Disease Patients (PONI)

Prevalence of Non-Alcoholic Fatty Liver Disease in Inflammatory Bowel Disease Patients: a Prospective Monocentric Study

Non-alcoholic Fatty Liver Disease (NAFLD) refers to a spectrum of disease characterized by the presence of more than 5% of steatosis in hepatocytes of individuals who consume little or no alcohol. It ranges from simple steatosis without evidence of inflammation, to the association of steatosis and inflammation with cellular necrosis, the so-called non-alcoholic steatohepatitis (NASH). NAFLD has become increasingly common in developed countries affecting up to 38% of the population. It is mostly but not exclusively associated with metabolic syndrome including obesity, insulin resistance, and hypertension. There is growing evidence of a close interaction between the gut and the liver "Gut-liver axis", particularly in the pathogenesis of NAFLD. The pathophysiological mechanism behind this association is not well understood but involves small intestinal bacterial overgrowth (SIBO), intestinal wall inflammation and increased permeability, all leading to systemic translocation of microbial metabolites including endotoxins and pro-inflammatory markers called Pathogen Associated Molecular Pattern (PAMPs). Thus, the gut-liver interaction, mediated by cytokines and inflammatory proteins seem to be the cornerstone of this complex liver disease.

Recent studies underlined the increased prevalence of NAFLD in the Inflammatory Bowel Disease (IBD) population, accounting for almost 32% of hepatic extra-intestinal manifestations of the disease. Several hypotheses have been proposed to explain the pathophysiology behind this association, encompassing chronic intestinal wall inflammation, increased intestinal permeability and altered gut microbiota or dysbiosis. To our knowledge, no studies have been conducted so far to investigate the correlation between intestinal disease activity (IBD flare versus remission state) and NAFLD incidence and behavior (progression versus regression of steato-fibrosis). We therefore aim to conduct a prospective paired study, on IBD patients followed at Saint-Pierre University Hospital, aiming to explore this correlation.

In this paired study design, patients will be their own controls over the course of their disease: An evaluation of NAFLD will be done for all patients during both phases of their inflammatory bowel disease: In the active phase and in remission phase. Our primary outcome is to assess NAFLD prevalence in the IBD population followed at our institution. Secondary outcomes will be to explore NAFLD prevalence and behavior (progression versus regression of steato-fibrosis) according to IBD activity, IBD type, IBD duration and types of IBD treatments.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Bowel Diseases; NAFLD; Fibrosis, Liver; Steatosis
• Intervention / Treatment: Diagnostic test: Transient elastometry

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Jennifer Aoun, Medical Doctor; Phone Number: +3225353296; Email: jennifer.aoun@stpierre-bru.be

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Recruiting
    • CHU Saint Pierre
    • Contact: Jennifer Aoun, Medical doctor; Phone Number: +32 25353296; Email: jennifer.aoun@stpierre-bru.be
    • Contact: Vinciane Muls, Medical doctor; Phone Number: +32 25354455; Email: vinciane.muls@stpierre-bru.be
    • Contact: Jennifer Aoun, Medical doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

IBD patients followed at Saint-Pierre University Medical Center, Brussels, Belgium

Description

Inclusion Criteria:

• Diagnosis of IBD based on clinical, endoscopic, and histological gounds according to the latest ECCO guidelines
• Willingness to provide informed consent for study participation

Exclusion Criteria:

• Presence of established liver disease (including autoimmune hepatitis, primary biliary cholangitis, primary biliary cirrhosis, hemochromatosis, Wilson's disease, positive serology for viral hepatitis B or C)
• History of hepatocellular carcinoma or liver transplantation
• History of excessive alcohol consumption defined as >3 units per day for women and > 5 units per day for men
• Pregnancy at the time of recruitment
• Failure to perform an elastography mesure or missing elastography data

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Baseline assessment; All patients with a confirmed diagnosis of IBD (cf. inclusion criteria) will have their demographic and clinical data collected during consultation via the medical record system Xcare/Abrumet. This include their age, gender, ethnicity, calculated BMI, alcohol consumption, smoking history, medical history (Hypertension, diabetes type II and dyslipidemia) and surgical history. Clinical data such as disease type, duration and IBD related current medications will be noted. The gastroenterologist will fill an assessment questionnaire in order to clinically assess the disease activity. This consists of Partial Mayo clinical score (pMayo) for Ulcerative Colitis and Harvey Bradshaw Index (HBI) for Crohn's disease. Remission is defined as a pMayo ≤ 1 or a HBI <5, mild disease is defined as pMayo between 2 and 4, or HBI between 5 and 7. Finally, moderate to severe disease is defined as pMayo ≥ 5, or HBI > 85. According to the data provided, patients will be classified into two sub-groups accor	Diagnostic test: Transient elastometry; Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) will be measured by transient liver elastometry "Fibroscan" to evaluate hepatic steatosis and fibrosis in all patients at baseline. Absence of steatosis S0 is defined as CAP <248 dB/m, mild steatosis S1 with CAP < 268 dB/m, and moderate to severe steatosis ≥ S2 is defined as CAP >280 dB/m. Liver fibrosis will be evaluated using the liver stiffness measurement (LSM) in kPa7.
Follow-up Assessment; Patients selected in the phase A of the study will be followed over time, through the course of their disease following the usual protocol for IBD patients follow up. They will undergo the same assessment when a change in the baseline intestinal disease activity occurs: This is defined as a progression from remission state to active disease state or vice versa. The assessment consists of the clinical questionnaire to be filled by the gastroenterologist during a follow up consultation (pMayo and HBI), routine blood tests for biochemical follow up of the disease activity, measurements of cytokines and inflammatory proteins (similar to phase A), FIB-4 score calculation and a repeat transient elastometry "Fibroscan".	Diagnostic test: Transient elastometry; Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) will be measured by transient liver elastometry "Fibroscan" to evaluate hepatic steatosis and fibrosis in all patients at baseline. Absence of steatosis S0 is defined as CAP <248 dB/m, mild steatosis S1 with CAP < 268 dB/m, and moderate to severe steatosis ≥ S2 is defined as CAP >280 dB/m. Liver fibrosis will be evaluated using the liver stiffness measurement (LSM) in kPa7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of NAFLD in the population of IBD patients followed at the University Hospital IBD clinic.	Prevalence of NAFLD in the population of IBD patients followed at the University Hospital IBD clinic.	From enrollement to the end of the study, up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavior of NAFLD according to the IBD activity	Behavior of NAFLD (progression versus regression of steato-fibrosis) according to IBD activity (active disease versus remission)	From enrollement to the end of the study, up to 12 months
NAFLD predictors in IBD patients	Independent predictors (risk factors) for NAFLD in our IBD patients study population such as particular demographics, IBD disease type, IBD disease duration, IBD treatments, patients' immunological profiles, and various inflammatory markers.	From enrollement to the end of the study, up to 12 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 30, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Fibrosis; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Intestinal Diseases; Liver Cirrhosis; Inflammatory Bowel Diseases
• Other Study ID Numbers: PONI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No