Background and Aim: Celiac disease (CD) is a chronic disorder resulting from an immune reaction to gluten in genetically predisposed individuals. Although several studies have linked CD to psychiatric diseases, there are limited data on this topic. Using a large database, we sought to describe the epidemiology of several psychiatric disorders in CD. Methods: We queried a multicenter database (Explorys Inc), an aggregate of electronic health record data from 26 major integrated healthcare systems from 2016 to 2020 consisting of 360 hospitals in the USA. A cohort of patients with a Systematized Nomenclature Of Medicine -Clinical Terms diagnosis of CD was identified. Multivariate analysis was performed using Statistical Package for Social Sciences version 25. Results: Of the 37 465 810 patients in the database between 2016 and 2020, there were 112 340 (0.30%) individuals with CD. When compared with patients with no history of CD, patients with CD were more likely to have a history of anxiety (odds ratio [OR]:

Background The appendix is the third most common place for neuroendocrine tumors (NETs) along the digestive tract and NETs are the most common neoplasms of the appendix. However, there are limited population-based data on the epidemiology of this disease. Using a large database, we sought to describe the epidemiology and risk association of NETs of the appendix. Method We queried a multi-institutional database (Explorys Inc., Cleveland, OH, USA), comprising 360 hospitals in the United States (US), for patients with a diagnosis of NETs of the appendix from 2014-2019. Results Of the 30,324,050 individuals in the database, 2020 patients had an appendiceal NET diagnosis (0.007%). The most common presenting symptoms included abdominal pain, nausea, vomiting and diarrhea. Patients with appendiceal NETs were more likely to be female (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.24-1.49), Caucasian (OR 2.71, 95%CI 2.40-3.07), with a history of smoking (OR 1.82, 95%CI 1.65-2.01), family history of primary gastrointestinal malignancy (OR 7.26, 95%CI 6.31-8.33), diagnosis of multiple endocrine tumor type 1 (OR 52.31, 95%CI 23.15-118.23), or neurofibromatosis type 1 (OR 16.37, 95%CI 7.24-37.01). Conclusions In a population-based study in the US, using the Explorys database, we found the overall prevalence of NETs of the appendix to be 7 per 100,000 persons. The incidence in the year January 2019-January 2020 was 0.4 per 100,000 individuals. These rates are higher than previously reported and may be more accurate, given the more comprehensive nature of the Explorys database.

Background The prevalence of fatty liver disease is potentially increasing in adolescents and young adults (AYAs) due to the obesity and alcohol pandemics. The aim of this study was to assess the prevalence of alcohol-associated fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) in a representative U.S. cohort utilizing transient elastography to directly measure hepatic steatosis and suspected fibrosis. Methods AYAs (age 15–39 years) with valid FibroScan® measurements in the National Health and Nutrition Examination Survey (NHANES) database (2017–2018) were included in the analyses. Those with viral hepatitis, pregnancy, or ALT/AST > 500 U/L were excluded. The population was divided into those with excessive alcohol consumption (ALQ130) and those without. Controlled attenuation parameter (CAP) score ≥ 248 dB/m was used to identify suspected ALD and NAFLD. In those with evidence of ALD, the following cutoffs of liver stiffness measurement (LSM) were used for suspected fibrosis: F ≥ F2 at LSM ≥ 7.5 kPa and F ≥ F3 at ≥ 9.5 kPa, respectively. In those with suspected NAFLD, the following LSM cutoffs were used: F ≥ F2 at 6.1 and F ≥ F3 at ≥ 7.1, respectively. Cutoffs were chosen based on published literature to maximize sensitivity. Results Comparing to those without, subjects with excessive alcohol consumption tended to be older (29.8 vs 28.5 years), have a higher BMI (29.3 vs 28.9 kg/m2), and be from a White ethnicity (65.3% vs. 55.4%). In subjects with excessive alcohol consumption, suspected ALD was present in 56.59% (95% CI 41.57–70.49). In those with suspected ALD, suspected significant fibrosis (F ≥ F2) was present in 12.3% (95% CI 4.74–28.34) and advanced fibrosis (F ≥ F3) was present in 6.31% (95% CI 0.69–39.55). Similarly, in subjects without excessive alcohol consumption, suspected NAFLD was present in 40.04% (36.64–43.54). In those with suspected NAFLD, suspected significant fibrosis (F ≥ F2) was present in 31.07% (27.25–35.16) and suspected advanced fibrosis (F ≥ F3) was present in 20.15% (16.05–24.99). Conclusion A significant percentage of AYAs are at risk for ALD and NAFLD and a subset of these subjects is at risk for significant fibrosis. Efforts should focus on increasing awareness of the prevalence of ALD and NAFLD in this population and to mitigate modifiable risk factors.

Background While there is higher prevalence of autoimmune, cholestatic and fatty liver disease in celiac disease (CeD), most data is from small-scale studies. We evaluated the prevalence and risk factors of the same using large cohort data. Methods A population-based cross-sectional study was conducted using Explorys, a multi-institutional database. Prevalence and risk factors of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and nonalcoholic fatty liver disease (NAFLD) in CeD were assessed. Results Out of 70 352 325 subjects, 136 735 had CeD (0.19%). The prevalence of AIH (0.32%), PBC (0.15%), PSC (0.004%) and NAFLD (0.7%) were high in CeD. After adjusting for age, gender, Caucasian race and anti-tissue transglutaminase antibody (anti-TTG), CeD subjects had higher odds of AIH [adjusted odds ratio (aOR) 7.06, 95% confidence interval (CI) 6.32–7.89] and PBC (aOR 4.16, 95% CI 3.46–5.0). Even after adjusting for CeD, anti-TTG positivity concurred with higher odds of AIH (aOR 4.79, 95% CI 3.88–5.92) and PBC (aOR 9.22, 95% CI 7.03–12.1). After adjusting for age, gender, Caucasian race, diabetes mellitus (DM), obesity, hypothyroidism and metabolic syndrome, there was higher prevalence of NAFLD in CeD, with the aOR in the presence of DM type 1 being 2.1 (95% CI 1.96–2.25), and in the presence of DM type 2 being 2.92 (95% CI 2.72–3.14). Conclusion Subjects with CeD are more likely to have AIH, PBC, PSC and NAFLD. AIH and PBC have higher odds in the presence of anti-TTG. The odds of NAFLD in CeD are high regardless of type of DM.

Backgrounds: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and metabolic syndrome conditions. However, a subset of NAFLD patients express a normal or low body mass index (lean NAFLD [L-NAFLD]). Our aim is to compare the prevalence of L-NAFLD to the obesity-associated NAFLD in the United States by assessing prevalence, potential risk factors, liver-related complications, and coronary artery disease outcomes. Methodology: A multicenter database (Explorys Inc.) of >70 million patients across the United States was screened. A cohort of patients with "nonalcoholic fatty liver" between 1999 and 2021 was identified. Two sub-cohorts of NAFLD patients were identified: those with a body mass index (BMI) < 25 kg/m 2 (L-NAFLD) and those with a BMI > 30 kg/m 2 (obesity-associated NAFLD). We excluded patients with age <18 and those who have viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis, alcoholic liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, and autoimmune hepatitis. Multivariate analysis was performed to adjust for confounders. Results: 68 892 260 individuals were screened. NAFLD prevalence was four per 100 000, and L-NAFLD prevalence was 0.6 per 100 000. Compared with those without, patients with L-NAFLD tended to be older (OR 2.16), females (OR 1.28), and smokers (OR 4.67) and of Asian race (OR 2.12). L-NAFLD patients were more likely to have acute coronary syndromes (OR 30.00) and metabolic syndrome (OR 2.31) despite the normal/low BMI. Esophageal varices and hepatocellular carcinoma risks were high in both cirrhosis patients. Conclusion: This is the largest study to assess L-NAFLD prevalence in the United States. L-NAFLD are at a significantly higher risk for acute coronary syndromes, esophageal varices, and hepatocellular carcinoma. with NAFLD, which is known as lean NAFLD (L-NAFLD).

Background: Gallbladder cancer (GBC) is the most common neoplasm of the biliary tract with the lowest rates of survival. Most GBCs are adenocarcinomas that arise from the epithelial lining of the gallbladder. There are limited data in the literature regarding the epidemiology of GBC. Using a large database, we aim to describe the epidemiology using a US population database. Methods: A multi-institutional database (Explorys Inc., Cleveland, OH, USA) was surveyed. A cohort of patients with a primary malignant neoplasm of gallbladder between 1999-2019 was identified. The prevalence rate was calculated and age-, race-, and sex-based distributions were described. Multivariate analysis was done to evaluate underlying associations. Results: Of the 56,197,690 individuals in the database, 4,790 individuals with GBC were identified with a prevalence rate of 8.5 per 100,000. Asian race has the highest prevalence of GBC (13.6/100,000). Patients with GBC were also more likely to be smokers, have a history of alcohol abuse, obesity, diabetes, cholelithiasis, chronic cholecystitis, primary sclerosing cholangitis (PSC), and chronic viral hepatitis. Conclusions: This is one of the largest US population studies to date evaluating the epidemiology of GBC. The 20-year period prevalence rate of GBC was 8.5 per 100,000. Patients with GBC were more likely to be elderly, females, obese, diabetic, and have chronic hepatobiliary disorders.

Background The association between celiac disease and inflammatory bowel disease (IBD) has been studied; however, the impact of IBD therapy on celiac disease is not known. Using a large database, we sought to describe the association of celiac disease and IBD and the impact of IBD treatment. Methods We queried a large multicenter database (Explorys Inc.), an electronic health record data aggregate from 26 American health care systems. We identified a cohort of patients with celiac disease and IBD between 1999 and 2020 and conducted a statistical analysis using a multivariate model. Results Of the 72,965,940 individuals in the database, 133,400 had celiac disease (0.18%), 191,570 (0.26%) had ulcerative colitis (UC), and 230,670 (0.32%) had Crohn disease (CD). Patients with IBD were more likely to have a diagnosis of celiac disease (odds ratio [OR], 13.680), with a greater association with CD. Treated patients with UC and with CD, respectively, had a lower risk association with celiac disease compared to those not undergoing IBD treatment, specifically corticosteroids (OR, 0.407 and 0.585), 5-aminosalicylates (OR, 0.124 and 0.127), immunomodulators (OR, 0.385 and 0.425), and anti-tumor necrosis factor drugs (OR, 0.215 and 0.242). There was no lower risk association in the vedolizumab group, but there was a higher risk association among the ustekinumab group. Conclusions In this large dataset, we showed a bidirectional association between celiac disease and IBD that was stronger with CD. Patients with IBD treated using corticosteroids, 5-aminosalicylates, immunomodulators, or anti-tumor necrosis factor drugs had a lower association with celiac disease. Additional studies are required to determine the underlying mechanisms for IBD therapy–related modification of celiac disease incidence.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistent AIM To evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy. METHODS Our cohort’s data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years. RESULTS Among the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table 1 . Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table 2 ). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303). CONCLUSION Hypothyroidism seems to be an independent risk factor for the development of NAFLD. Thyroid hormone replacement did not provide a statistically significant risk reduction. Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.