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.
None
age >18 and <65 years;
subjects with wheat-dependent symptoms, both gastrointestinal and extra-intestinal;
negativity of IgA and IgG anti-deamidated gliadin peptide (DPG) antibodies, immunoglobulin (Ig)A and IgG anti-tissue transglutaminase (tTG) antibodies, and anti-endomysial antibodies (EMA);
absence of duodenal villous atrophy, documented in all patients carrying the human leukocyte antigen (HLA) DQ2 and/or DQ8 haplotypes (therefore regardless of the negativity of celiac disease (CeD)-specific serum antibodies), evaluated when the patients had consumed a minimum of 100g of pasta and/or bread a day, for at least 45 days;
This is a prospective multicenter study conducted on patients with Non-Celiac Wheat Sensitivity (NCWS), consecutively diagnosed by double-blind placebo-controlled challenge (DBPCC) with wheat, from January 2024, in the outpatient clinics of two Internal Medicine Units: University Hospital of Palermo, Italy, and "Villa-Sofia-Cervello" Hospital, Palermo, Italy. The records of the patients were prospectively collected and analyzed, together with those of two control populations of Irritable Bowel Syndrome/Functional Dyspepsia (IBS/FD) unrelated to food (including wheat) allergies/intolerances, and Celiac Disease (CeD), consecutively recruited in the same period and in the same outpatient clinics, before diagnosis (baseline) and after 1 year of follow-up.
Case-control
Prospective
Prevalence and severity of liver steatosis and fibrosis,
Diagnostic testTo 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.
Prevalence and severity of liver steatosis and fibrosis by Ultrasound examination
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
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
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
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.
Click on the lead sponsor to view all of their trials.
