Prevalence and Risk Factors of Liver Steatosis and Fibrosis in Non-Celiac Wheat Sensitivity Patients: a Prospective Study
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.
• 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;
• absence of IgE-mediated wheat allergy (WA): negative skin prick-test and/or specific serum IgE assay for wheat, gluten and gliadin);
• resolution of symptoms on a strict standard elimination diet (i.e. extended oligoantigenic, excluding wheat, cow's milk, egg, tomato and chocolate and other foods self-reported by the patient as causing symptoms), followed for at least 4 weeks, and the recurrence of the same symptoms after double-blind placebo-controlled challenge (DBPCC) with wheat (for further details see below);
• complete medical records;
• duration of follow-up longer than 12 months after initial diagnosis, with at least 2 outpatient visits during the follow-up period.
• age \>18 and \<65 years;
• subjects diagnosed with IBS/FD and other functional gastrointestinal disorders, according to the Rome IV classification, 1 who did not specifically report symptoms/signs, whether gastrointestinal or extra-intestinal, following ingestion of wheat or other foods and who did not respond to gluten-free diet (GFD).
• age \>18 and \<65 years;
• subjects with gastrointestinal and extra-intestinal wheat-dependent symptoms that meet the diagnostic criteria of CeD 2: positivity of anti-tTG IgA and/or IgG antibodies and evidence of villous atrophy, according to the Marsh-Oberhuber classification, demonstrated by histology on duodenal biopsy;
• clinical response to the GFD: resolution of gastrointestinal and/or extra-intestinal symptoms.