Celiac Disease, Functional Dyspepsia, Irritable Bowel Syndrome, Metabolic Dysfunction-Associated Steatotic Liver Disease, Non Celiac Wheat Sensitivity
Conditions
Keywords
non-celiac wheat sensitivity, metabolic dysfunction-associated steatotic liver disease
Brief summary
Hypothesizing an intestinal barrier impairment as a common pathophysiological substrate of both Non Celiac Wheat Sensitivity (NCWS) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MAFLD), in a retrospective cohort study (data not yet published), demographic, clinical, laboratory and histology data of NCWS patients at the time of diagnosis, were analyzed and compared to control subjects with Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) and freshly diagnosed Celiac Disease (CeD). NCWS diagnosis was performed by a double-blind placebo-controlled wheat challenge. Steatosis was confirmed by ultrasound examination. Our retrospective data showed that the frequency of liver of steatosis was lower in NCWS than in IBS patients. In addition, it seems that pre-diagnosis avoidance of wheat in NCWS correlates with protection from steatosis. A subset of NCWS patients, recently exposed to wheat, with clinical features suggesting increased IP, seems to be predisposed to liver steatosis and fibrosis. To validate the results of the retrospective study, the researchers planned the present prospective study, to analyze the prevalence of liver steatosis and fibrosis, evaluated by ultrasound (US) examination, FibroScan analysis \[CAP (Controlled Attenuation Parameter) and LSM (Liver Stiffness Measurement) values\], FIB-4 (Fibrosis-4) index, and NFS \[Non-alcoholic fatty liver disease (NAFLD) Fibrosis Score\], in patients with NCWS at the time of diagnosis, comparing them with two control populations of newly diagnosed IBS/FD and CeD patients.
Detailed description
Many people with symptoms similar to inflammatory bowel syndrome (IBS) or functional dyspepsia (FD) follow a wheat-free diet (WFD) because it is subjectively better tolerated, even if they do not suffer from celiac disease (CeD) or wheat allergy. This condition, originally named non-celiac gluten sensitivity, has been redefined as non-celiac wheat sensitivity (NCWS), because its clinical manifestations can be triggered by a spectrum of non-gluten wheat proteins, such as wheat amylase-trypsin inhibitors (ATIs), that cause a delayed type - non-IgE-mediated food allergy associated with an intestinal mucosa barrier (IB) defect. Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease in countries with excess nutrient supply. In addition to the main etiopathogenetic factors, other factors must be implicated: nutrition, intestinal microbiota, intestinal permeability (IP) and the gut-liver axis might play a key role due to the translocation of nutrient-derived peptides and microbial products into the intestinal lamina propria. Here, the liver is prominently exposed to the inflammatory intestinal signals via the mesenteric-portal venous system, that significantly contributes to the onset of MASLD, metabolic disfunction-associated steatohepatitis (MASH) and liver fibrosis. In patients with NCWS, intake of wheat and wheat ATIs (Amylase-Trypsin Inhibitors) increases IP, promotes intestinal dysbiosis, and activates the gastrointestinal and extra-intestinal immune response. Hypothesizing an intestinal barrier impairment as a common pathophysiological substrate of both NCWS and MAFLD, in a retrospective cohort study (data not yet published), demographic, clinical, laboratory and histology data of NCWS patients at the time of diagnosis, were analyzed and compared to control subjects with IBS/FD and freshly diagnosed CeD. NCWS diagnosis was performed by a double-blind placebo-controlled wheat challenge. Steatosis was confirmed by ultrasound examination. Our retrospective data showed that the frequency of liver of steatosis was lower in NCWS than in IBS patients. In addition, it seems that pre-diagnosis avoidance of wheat in NCWS correlates with protection from steatosis. A subset of NCWS patients, recently exposed to wheat, with clinical features suggesting increased IP, seems to be predisposed to liver steatosis and fibrosis. To validate the results of the retrospective study, the researchers planned the present prospective study, to analyze the prevalence of liver steatosis and fibrosis, evaluated by ultrasound examination, FibroScan analysis \[CAP (Controlled Attenuation Parameter) and LSM (Liver Stiffness Measurement) values\], FIB-4 (Fibrosis-4) index, and NFS \[Non-alcoholic fatty liver disease (NAFLD) Fibrosis Score\], in patients with NCWS at the time of diagnosis, comparing them with two control populations of newly diagnosed IBS/FD and CeD patients.
Interventions
DIAGNOSTIC_TESTPrevalence and severity of liver steatosis and fibrosis,
To establish the prevalence and severity of liver steatosis and fibrosis, the researchers will analyze data from the UltraSound (US) and FibroScan examinations, and from two validate scores performed before diagnosis.
Sponsors
University of Palermo
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
The inclusion/
Exclusion criteria
used to select the study population have been previously validated in other retrospective studies. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence and severity of liver steatosis and fibrosis by Ultrasound examination | At baseline, before diagnosis | Steatosis was evaluated according to international validated Ultrasound (US) criteria and classified as follows: absent (score 0), when the echostructure of the liver was normal; mild (score 1), when there was a mild, diffuse increase in hepatic echogenicity, with normal visualization of the portal vein wall and diaphragm; moderate (score 2), in the case of a moderate increase in hepatic echogenicity, with a less clear/slightly altered demarcation of the portal vein wall and diaphragm; severe (score 3), in the case of markedly increased hepatic echogenicity, with little or no visualization of the portal vein wall, diaphragm and posterior part of the right hepatic lobe. |
| Prevalence and severity of liver steatosis by FibroScan analysis | At baseline, before diagnosis | FibroScan analysis provides CAP (Controlled Attenuation Parameter, normal validated cut-offs of ≤275 dB/m) and LSM (Liver Stiffness Measurement, normal validated cut-offs of ≤5.5 kPa) values for liver steatosis and fibrosis, respectively. Detailed scores were, for CAP, Normal values ≤275 dB/m; Mild Steatosis (S1): 275-290 dB/m; Moderate Steatosis (S2): 290-302 dB/m; Severe Steatosis (S3): ≥302 dB/m. For LSM, F0 (No fibrosis): ≤5.5-6.0 kPa; F1 (Mild fibrosis): 5.6-7.0 kPa; F2 (Moderate/significant fibrosis): 7.1-9.4 kPa; F3 (Severe/Advanced fibrosis): 9.5-14.5 kPa; F4 (Cirrhosis): ≥14.6 kPa. |
| Prevalence and severity of liver steatosis and fibrosis by FIB-4 | At baseline, before diagnosis | A validated score was used to assess the risk for significant liver fibrosis in MASLD: the FIB-4 index. Based on this test, our cohort was stratified as being at low- or moderate-high-risk for advanced fibrosis, based on validated cut-off of ≤1.3 for a low-risk and of ≥1.4 for moderate-high-risk. |
| Prevalence and severity of liver steatosis and fibrosis by NFS | At baseline, before diagnosis | Another validated score was used to assess the risk for significant liver fibrosis in MASLD: the NFS. Based on this test, our cohort was stratified as being at low- or moderate-high-risk for advanced fibrosis, based on validated cut-off ≤1.455 for NFS for a low-risk and of ≥1.456 for moderate-high-risk. |
Countries
Italy
Contacts
CONTACTAntonio Carroccio, MD
STUDY_DIRECTORPasquale Mansueto, MD
University of Palermo
STUDY_CHAIRAurelio Seidita, MD
University of Palermo
Outcome results
None listed