ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY.

WHAT IS ALREADY KNOWN: •The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

INCREASED RISK OF COLORECTAL CANCER IN PATIENTS WITH CHRONIC TOPHACEOUS GOUT: A POPULATION-BASED STUDY.

•The study aims to investigate the risk of developing Colorectal cancer in patients with a history of chronic tophaceous gout. •A retrospective cohort analysis of adults extracted from a validated multicenter and research platform database from hospitals in the United States was utilized. •The risk of Colorectal cancer was statistically significantly increased in male gender, smokers, alcoholics, obese, type 2 Diabetic, and chronic tophaceous gout patients. •The risk of developing Colorectal cancer was significantly higher in patients who have a history of Chronic tophaceous gout while accounting for potential confounding variables. Background - Colorectal cancer is the third most common type of cancer in both men and women and ranks second as the most common cause of cancer death in the United States. Classic risk factors include tobacco smoking, high alcohol consumption, physical inactivity and excess body weight. A prospective study found that an elevated serum uric acid was associated with higher rates of cancer-associated polyps. Interestingly, other studies found an association between elevated levels of serum uric acid and other types of cancer including colorectal cancer. Objective - Our study aimed to evaluate whether patients with chronic tophaceous gout had an increased risk of developing colorectal cancer. Methods - A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have had a history of familial adenomatous polyposis, a family history of colon cancer, and those diagnosed with inflammatory bowel disease were excluded from the analysis. The risk of developing colon cancer was calculated using a multivariate regression analysis to account for potential confounders. Results - 80,927,194 individuals were screened in the database and 70,177,200 were selected in the final analysis after accounting for inclusion and exclusion criteria. Type 2 diabetics (28.57%), smokers (10.98%), obese individuals (18.71%), alcoholics (3.13%), and patients who have had a diagnosis of chronic tophaceous gout were more common in the colon cancer group compared to those without the malignancy. Using multivariate regression analysis, risk of colon cancer was calculated for male gender (OR: 1.02; 95%CI: 1.01-1.03), smokers (OR: 1.54; 95%CI: 1.52-1.56), alcoholics (OR: 1.40; 95%CI: 1.37-1.43), obese patients (OR: 1.52; 95%CI: 1.50-1.54), type 2 diabetic individuals (OR: 3.53; 95%CI: 3.50-3.57), and those who have had a diagnosis of chronic tophaceous gout (OR: 1.40; 95%CI: 2.48-3.23). Conclusion - As expected, patients with colon cancer were found to have a higher prevalence in males, obese, tobacco and alcohol users. We also demonstrated that patients with gout have a significantly higher prevalence of CRC than those who do not before and after adjusting for metabolic risk factors. In fact, uric acid was found to induce production of reactive oxygen species, thus potentially promoting tumorigenesis. It would be interesting to assess the prevalence of colon cancer in patients with gout who have a serum uric acid that is less than 7 mg/dL. This might promote a tighter control of serum uric acid levels in this population in order to decrease the risk of colon cancer.

Risco aumentado de câncer colorretal em pacientes com gota tofácea crônica: um estudo populacional / Increased risk of colorectal cancer in patients with chronic tophaceous gout: a population-based study

ABSTRACT Background: Colorectal cancer is the third most common type of cancer in both men and women and ranks second as the most common cause of cancer death in the United States. Classic risk factors include tobacco smoking, high alcohol consumption, physical inactivity and excess body weight. A prospective study found that an elevated serum uric acid was associated with higher rates of cancer-associated polyps. Interestingly, other studies found an association between elevated levels of serum uric acid and other types of cancer including colorectal cancer. Objective: Our study aimed to evaluate whether patients with chronic tophaceous gout had an increased risk of developing colorectal cancer. Methods: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have had a history of familial adenomatous polyposis, a family history of colon cancer, and those diagnosed with inflammatory bowel disease were excluded from the analysis. The risk of developing colon cancer was calculated using a multivariate regression analysis to account for potential confounders. Results: 80,927,194 individuals were screened in the database and 70,177,200 were selected in the final analysis after accounting for inclusion and exclusion criteria. Type 2 diabetics (28.57%), smokers (10.98%), obese individuals (18.71%), alcoholics (3.13%), and patients who have had a diagnosis of chronic tophaceous gout were more common in the colon cancer group compared to those without the malignancy. Using multivariate regression analysis, risk of colon cancer was calculated for male gender (OR: 1.02; 95%CI: 1.01-1.03), smokers (OR: 1.54; 95%CI: 1.52-1.56), alcoholics (OR: 1.40; 95%CI: 1.37-1.43), obese patients (OR: 1.52; 95%CI: 1.50-1.54), type 2 diabetic individuals (OR: 3.53; 95%CI: 3.50-3.57), and those who have had a diagnosis of chronic tophaceous gout (OR: 1.40; 95%CI: 2.48-3.23). Conclusion: As expected, patients with colon cancer were found to have a higher prevalence in males, obese, tobacco and alcohol users. We also demonstrated that patients with gout have a significantly higher prevalence of CRC than those who do not before and after adjusting for metabolic risk factors. In fact, uric acid was found to induce production of reactive oxygen species, thus potentially promoting tumorigenesis. It would be interesting to assess the prevalence of colon cancer in patients with gout who have a serum uric acid that is less than 7 mg/dL. This might promote a tighter control of serum uric acid levels in this population in order to decrease the risk of colon cancer.

RESUMO Contexto: O câncer colorretal é o terceiro tipo mais comum de câncer em homens e mulheres e ocupa o segundo lugar como a causa mais comum de morte por câncer nos EUA. Os fatores de risco clássicos incluem tabagismo, alto consumo de álcool, inatividade física e excesso de peso corporal. Um estudo prospectivo descobriu que um ácido úrico sérico elevado estava associado a taxas mais altas de pólipos associados ao câncer. Curiosamente, outros estudos encontraram uma associação entre níveis elevados de ácido úrico sérico e outros tipos de câncer, incluindo o câncer colorretal. Objetivo: Nosso estudo teve como objetivo avaliar se os pacientes com gota tofácea crônica tinham um risco aumentado de desenvolver câncer colorretal. Métodos: Utilizou-se um banco de dados validado multicêntrico e de plataforma de pesquisa de mais de 360 hospitais de 26 diferentes sistemas de saúde nos Estados Unidos para a construção deste estudo. Foram incluídos pacientes com 18 anos ou mais. Indivíduos com histórico de polipose adenomatosa familiar, histórico familiar de câncer de cólon e aqueles diagnosticados com doença inflamatória intestinal foram excluídos da análise. O risco de desenvolver câncer de cólon foi calculado usando uma análise de regressão multivariada para contabilizar possíveis confusões. Resultados: 80.927.194 indivíduos foram rastreados no banco de dados e 70.177.200 foram selecionados na análise final após considerar critérios de inclusão e exclusão. Diabéticos tipo 2 (28,57%), fumantes (10,98%), indivíduos obesos (18,71%), alcoólatras (3,13%) e pacientes que tiveram diagnóstico de gota tofácea crônica foram mais comuns no grupo de câncer de cólon em comparação com aqueles sem a malignidade. Usando a análise de regressão multivariada, o risco de câncer de cólon foi calculado para o sexo masculino (OR: 1,02; IC95%: 1,01-1,03), fumantes (OR: 1,54; IC95%: 1,52-1,56), alcoólatras (OR: 1,40; IC95%: 1,37-1,43), pacientes obesos (OR: 1,52; IC95%: 1,50-1,54), indivíduos diabéticos tipo 2 (OR: 3,53; IC95%: 3,50-3,57), e aqueles que tiveram diagnóstico de gota tofácea crônica (OR: 1,40; IC95%: 2,48-3,23). Conclusão: Como esperado, os pacientes com câncer de cólon foram encontrados com maior prevalência em homens, obesos, usuários de tabaco e álcool. Demonstramos também que os pacientes com gota têm uma prevalência significativamente maior de câncer colorretal do que aqueles que não a têm, antes e após o ajuste para fatores de risco metabólicos. De fato, descobriu-se que o ácido úrico induz a produção de espécies reativas de oxigênio, promovendo assim potencialmente a tumorigênese. Seria interessante avaliar a prevalência de câncer de cólon em pacientes com gota que têm um ácido úrico sérico inferior a 7 mg/dL. Isso poderia promover um controle mais rígido dos níveis de ácido úrico sérico nesta população para diminuir o risco de câncer de cólon.

Medicamentos antidepressivos estão associados a um risco aumentado de infecção hospitalar por Clostridioides difficile: um estudo populacional / Antidepressant medications are associated with increased risk of hospital-acquired clostridioides difficile infection: a population-based study

ABSTRACT Background: During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications. Methods: Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results: The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion: In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

RESUMO Contexto: Na última década, a infecção por Clostridioides difficile (ICD) tornou-se a causa mais comum de diarreia associada a antibióticos. Vários fatores de risco foram implicados. Existem evidências dispersas na literatura sobre a associação da ICD com o uso de medicamentos antidepressivos. Portanto, pretendemos investigar se o risco de desenvolver infecção adquirida na comunidade por Clostridioides difficile aumenta em pacientes que usam medicamentos antidepressivos. Métodos: Pacientes que foram hospitalizados foram incluídos em nossa coorte. Indivíduos com menos de 18 anos foram excluídos. Uma análise de regressão multivariada foi realizada para calcular o risco de ICD, considerando possíveis confusões. Resultados: O risco de ICD em pacientes hospitalizados foi maior em indivíduos diagnosticados com doença inflamatória intestinal (OR: 4,44; IC95%: 4,35-4,52) e em pacientes que usavam clindamicina (OR: 1,55; IC95%: 1,53-1,57), antibióticos beta-lactâmicos (OR: 1,62; IC95%: 1,60-1,64), PPI (OR: 3,27; IC95%: 3,23-3,30), trazodona (OR: 1,31; IC95%: 1,29-1,33), nortriptilina (OR: 1,25; IC95%: 1,21-1,28) e mirtazapina (OR: 2,50; IC95%: 2,46-2,54). Depois de controlar as covariáveis, o risco de ICD não aumentou em pacientes que estavam tomando fluoxetina (OR: 0,94; IC95%: 0,92-0,96). Conclusão: Em contrário à fluoxetina; mirtazapina, nortriptilina e trazodona foram associados a um risco aumentado de ICD em pacientes hospitalizados.

The impact of nonalcoholic fatty liver disease on inflammatory bowel disease-related hospitalization outcomes: a systematic review.

Evidence suggests that patients with inflammatory bowel disease are at higher risk of developing nonalcoholic fatty liver disease (NAFLD). However, there is limited information currently available on how NAFLD may affect the clinical course of IBD. Thus, we conducted a systematic review to evaluate the impact of NAFLD on IBD-related hospitalization outcomes. All observational studies assessing IBD-related hospitalization outcomes in patients with NAFLD were included. Exclusion criteria were studies published in languages other than English or French, or those involving pediatric population. Outcomes included IBD-related hospitalization and readmission rates, need for surgery, length of stay, inpatient mortality, and costs. Overall, 3252 citations were retrieved and seven studies met the inclusion criteria (1 574 937 patients); all were observational, of high quality, and originated in the United States. Measurable outcomes reported in these studies were few and with insufficient similarity across studies to complete a quantitative assessment. Only one study reports NAFLD severity. Two studies suggested a higher rate of hospitalization for patients with both NAFLD and IBD compared to IBD alone (incidence rate ratio of 1.54; 95% confidence interval: 1.33-1.79). This is the first systematic review to date that evaluates any possible association of NAFLD with IBD-related hospitalization outcomes. Despite the paucity and low quality of available data, our findings indicate that NAFLD may be associated with worse outcomes amongst IBD patients (especially Crohn's disease). Further and higher certainty of evidence is needed for better characterization of such clinical impact.

Prevalence of autoimmune, cholestatic and nonalcoholic fatty liver disease in celiac disease.

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.

Cirrhotic patients on proton pump inhibitors are at a twofold risk of spontaneous bacterial peritonitis independently of gastrointestinal bleeding: a population-based retrospective study.

Background: Recent findings suggest that cirrhotic patients on proton pump inhibitors (PPIs) are at a higher risk for developing spontaneous bacterial peritonitis (SBP) than non-PPI users. We aimed to identify whether PPI use is an independent risk factor for the development of SBP among cirrhotic patients in the United States (US). Methods: We enrolled a retrospective cohort using a validated multicenter database. Patients with a SNOMED-CT diagnosis of "cirrhosis" between 1999 and 2022 were identified. All patients below 18 years of age were excluded. We calculated the prevalence of individuals using PPIs in the total US population and in cirrhotic patients from 1999 to date, and the incidence of SBP in the past year. Finally, we constructed a multivariate regression model, controlling for multiple covariates. Results: The final analysis included 377,420 patients. The 20-year-period prevalence of SBP in patients with cirrhosis was 3.54% and the prevalence of patients using PPIs in the US population was 12,000 per 100,000 people (12.00%). The 1-year incidence of SBP in cirrhotic patients using PPIs was 2500 per 100,000 people. After accounting for confounders, the risk of SBP was higher among males, patients with a diagnosis of gastrointestinal bleeding, and those using ß-blockers and PPIs. Conclusions: To date, this is the largest cohort used to examine the prevalence of SBP among cirrhotic patients in the US. PPI use and hepatic encephalopathy offered the highest risk for the development of SBP, independently of gastrointestinal bleeding. Focusing on judicious PPI use should be encouraged among cirrhotic patients.

Splenic Subcapsular Hematoma After Endoscopic Retrograde Cholangiopancreatography.

The complications of endoscopic retrograde cholangiopancreatography (ERCP) are numerous and mainly intraluminal. We present a unique case of a patient who developed splenic hematoma after ERCP. A 41-year-old woman was hospitalized for evaluation of chronic abdominal pain, for which she underwent an ERCP. The next day, the patient developed hemorrhagic shock. She was found to have a large ruptured subcapsular splenic bleed. Splenic artery embolization was performed, and the patient was stabilized. In conclusion, a high index of suspicion should be kept when managing patients presenting with unstable vital signs and/or acute anemia after ERCP.

Increased Risk of Colorectal Cancer in Patients With Celiac Disease: A Population-Based Study.

BACKGROUND AND AIM: The association between celiac disease (CD) and the development of small bowel lymphoproliferative disorders and esophageal adenocarcinoma has been established in the literature. However, there is only a little evidence demonstrating an increased risk of colorectal cancer (CRC) in patients with CD. Hence, we conducted a cross-sectional population-based study to evaluate the risk of developing CRC in patients who have had a diagnosis of CD. METHODOLOGY: We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health records from 26 major integrated US healthcare systems. Patients aged 18-65 years were included. Patients with inflammatory bowel disease (IBD) were excluded. Multivariate analysis using backward stepwise logistic regression was performed to calculate the risk of developing CRC in potential confounders. A two-sided P-value <0.05 was considered statistically significant. RESULTS: 79,843,332 individuals were screened in the database and 47,400,960 were selected in the final analysis after accounting for inclusion and exclusion criteria. Using a stepwise multivariate regression analysis, the odds of having CRC among patients with CD was 10.18 (95% CI 9.72-10.65) (P-value <0.001). The odds also remained high among males 1.49 (95% CI 1.36-1.63), African Americans 1.51 (95% CI 1.35-1.68), patients who have type 2 diabetes mellitus (T2DM) 2.71 (95% CI 2.66-2.76), are smokers 2.49 (95% CI 2.44-2.54), are obese 2.21 (95% CI 2.17-2.25), and are alcoholic 1.72 (95% CI 1.66-1.78). CONCLUSION: Our study demonstrates that patients with CD are frequently found to have CRC even when adjusting for common risk factors. This adds to the literature and helps spread awareness to clinicians that the effects of CD are not only limited to the small bowel as the disease tends to involve other parts of the gastrointestinal tract also, especially the colon. The threshold to screen patients with CD should be considered to be lowered.

Non-alcoholic steatohepatitis is independently associated with a history of gestational diabetes mellitus.

BACKGROUND AND AIM: A recent study has demonstrated that women with gestational diabetes mellitus (GDM) are more likely to develop non-alcoholic fatty liver disease than those without GDM. In contrary to non-alcoholic fatty liver, the association of GDM with non-alcoholic steatohepatitis (NASH) has still not been well established in the current literature. Therefore, we aim to evaluate the association of a history of GDM and the development of NASH throughout their lives independently of type 2 diabetes mellitus (T2DM). METHODS: A validated research database of more than 360 hospitals was utilized to construct this study. Adult females included were divided into two groups: those with NASH (case) and individuals without NASH (control). Regression analysis was performed to account for potential cofounders. RESULTS: There were 70 632 640 individuals above the age of 18 years screened in the database. In patients with a history of GDM, NASH was most prevalent in middle age people compared with NASH alone, which was more prevalent in people aged 65 years and above. Compared with those without, patients with NASH tend to be Caucasian (odds ratio [OR]: 2.13), obese (OR: 4.83), have a history of GDM (OR: 1.23), diagnosed with hyperlipidemia (OR: 2.59), T2DM (OR: 4.52), metabolic syndrome (OR: 3.07), polycystic ovaries disease (OR: 1.72), and hypothyroidism (OR: 1.59). CONCLUSION: We demonstrated for the first time an increased odd of developing NASH in women who have had a diagnosis of gestational diabetes mellitus throughout their lives independently of any other factors that could interfere with the results.

Epidemiology and risk of colorectal cancer in patients with a history of Helicobacter pylori infection: a population-based study.

Background: Numerous modifiable risk factors have been associated with colon cancer. Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide and the strongest known risk factor for gastric cancer. We aim to assess whether the risk of colorectal cancer (CRC) is higher in patients with a history of H. pylori infection. Methods: A validated multicenter and research platform database of more than 360 hospitals was queried. Patients aged 18-65 years were included in our cohort. We excluded all patients who had previously had a diagnosis of inflammatory bowel disease or celiac disease. Univariate and multivariate regression analyses were used to calculate CRC risk. Results: A total of 47,714,750 patients were selected after application of the inclusion and exclusion criteria. The 20-year-period prevalence rate of CRC in the United States population from 1999 to September 2022 was 370 of 100,000 individuals (0.37%). According to multivariate analysis, the risk of CRC was higher in smokers (odds ratio [OR] 2.52, 95% confidence interval [CI] 2.47-2.57), obese patients (OR 2.26, 95%CI 2.22-2.30), those with irritable bowel syndrome (OR 2.02, 95%CI 1.94-2.09), or type 2 diabetes mellitus (OR 2.89, 95%CI 2.84-2.95), and patients who had a diagnosis of H. pylori infection (OR 1.89, 95%CI 1.69-2.10). Conclusion: We provide the first evidence from a large population-based study demonstrating an independent association between a history of H. pylori infection and CRC risk.

Prevalence of non-alcoholic fatty liver disease in patients with nephrotic syndrome: A population-based study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome (NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD. AIM: To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS. METHODS: A large multicenter database (Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of "Non-Alcoholic fatty liver disease" using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type II diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. RESULTS: Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval (95%CI) 13.67-16.10], 17.05 (95%CI 16.78-17.32), 6.99 (95%CI 6.87-7.11), 13.61 (95%CI 13.38-13.84), 19.19 (95%CI 18.89-19.50), 29.09 (95%CI 28.26--29.95), and 9.05 (95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85 (95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio (OR) 3.84], hypothyroidism (OR 1.57), obesity (OR 5.10), hyperlipidemia (OR 3.09), metabolic syndrome (OR 3.42) and chronic kidney disease (OR 1.33). CONCLUSION: Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.

Increased Risk of Non-Alcoholic Steatohepatitis in Patients With Inflammatory Bowel Disease: A Population-Based Study.

Background and objective The global health burden of inflammatory bowel disease (IBD) stems from its increasing incidence over the years. Comprehensive studies on the topic hypothesize that IBD plays a more dominant in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In light of this, we conducted this study with the aim of assessing the prevalence and risk factors of developing NASH in patients who have had a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). Methodology A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized for conducting this study. Patients aged 18-65 years were included. Pregnant patients and individuals diagnosed with alcohol use disorder were excluded. The risk of developing NASH was calculated using a multivariate regression analysis to account for potential confounding variables including male gender, hyperlipidemia, hypertension, type 2 diabetes mellitus (T2DM), and obesity. A two-sided p-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results A total of 79,346,259 individuals were screened in the database and 46,667,720 were selected for the final analysis based on the inclusion and exclusion criteria. Using multivariate regression analysis, the risk of developing NASH among patients with UC and CD was calculated. The odds of having NASH among patients with UC was 2.37 (95% CI: 2.17-2.60, p<0.001). Similarly, the odds of having NASH were high in patients with CD as well, at 2.79 (95% CI: 2.58-3.02, p<0.001). Conclusion Based on our findings, patients with IBD have an increased prevalence and higher odds of developing NASH after controlling for common risk factors. We believe that a complex pathophysiological relationship exists between both disease processes. Further research is required to establish appropriate screening times to enable earlier disease identification and thereby improve patient outcomes.

Prevalence and Risk Factors Associated With Inflammatory Bowel Disease in Patients Using Proton-Pump Inhibitors: A Population-Based Study.

Background and aim Proton pump inhibitor (PPI) is a heavily prescribed medication in the United States that is used to treat several gastrointestinal disorders. Although it has been considered to be safe compared to other medications, multiple gastrointestinal side effects have been reported. These effects of PPIs might stem from the progressive alteration of the intestinal microbiome. Patients with inflammatory bowel disease (IBD) using PPI are also seen to be less likely to achieve remission. However, in the current literature, there is very little evidence of the risk of developing IBD in patients who have been using PPIs. Therefore, our aim was to perform a cross-sectional population-based study with in-depth analysis to assess the prevalence and risk factors of IBD amongst PPI users in the United States. Methodology  A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. A cohort of patients with a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) between 1999-2022 was identified using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Patients aged 18 to 65 years were included. We excluded any individual who had a diagnosis of chronic liver disease, autoimmune disease (excluding IBD), or cancer. The risk of IBD was calculated using a multivariate regression analysis to account for potential confounders including non-steroidal anti-inflammatory drugs (NSAIDs) use, smoking, patients who have had a diagnosis of alcoholism, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and metabolic syndrome. A two-sided P-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results  A total of 79,984,328 individuals were screened in the database and 45,586,150 patients were selected in the final analysis after accounting for inclusion and exclusion criteria. Using multivariate regression analysis, the risk of developing UC and CD was calculated. The odds of having UC amongst patients on PPI was 2.02 (95%CI 1.98-2.06), P-value <0.001. Similarly, the odds of having CD were high amongst PPI users (OR 2.79, 95%CI 2.75-2.84), P- value <0.001 Conclusion  Our study demonstrates that patients on PPIs are frequently found to have UC and CD even when adjusting for common risk factors. Hence, we urge clinicians to be aware of this association in order to limit unnecessary prescriptions of PPIs, especially for patients who are at risk for autoimmune diseases.

Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population-based study and review of literature.

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/m2 (L-NAFLD) and those with a BMI > 30 kg/m2 (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.

The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES 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.

The epidemiology of non-alcoholic steatohepatitis (NASH) in the United States between 2010-2020: a population-based study.

INTRODUCTION AND OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that can progress to liver cirrhosis, liver failure and hepatocellular carcinoma. It is the second leading cause of liver transplant in the US. We aim to investigate the prevalence, demographics and risk factors NASH patients in the US. PATIENTS AND METHODS: We used a large database (Explorys IBM) that aggregates electronic health records from 26 nationwide healthcare systems. We identified adults with NASH between 2010-2020. Demographics including age, gender and race were collected. NASH risk factors including Diabetes Millets (DM), Hyperlipidemia (HLD), Hypertension (HTN) and Obesity were also collected. Cochran-Armitage test was used to assess the statistical significance of year-by-year trend. Univariable and multivariable logistic regression were used to estimate the odds ratio (OR) of risk factors. RESULTS: NASH annual prevalence rate increased from 1.51% in 2010 to 2.79% in 2020 (p < 0.0001). The proportion of patients with NASH by gender was 54.1% female vs 45.9% male (OR 1.04 [0.91-1.11]). Caucasian had higher odds of NASH than non-Caucasian (OR 1.42 [1.31-1.54]). NASH is strongly associated with DM and obesity (OR 18.61 [17.35-19.94]) and (OR 20.97 [17.87-23.21]), respectively. Other components of metabolic syndrome were associated with NASH to a lesser degree; HTN (OR 3.24 [3.20-3.28]) and HLD (OR 4.93 [4.85-4.01]). CONCLUSION: The prevalence of NASH has significantly increased in the US in the last decade. This is likely related to the increased prevalence of risk factors as well as increased awareness of the disease.

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study.

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.

The incidence of COVID-19 in patients with metabolic syndrome and non-alcoholic steatohepatitis: A population-based study.

BACKGROUND: The novel coronavirus disease (COVID-19) emerged from China in 2019 and rapidly spread worldwide. Patients with metabolic comorbid conditions are more susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Metabolic syndrome is a constellation of interlinked metabolic risk factors that predispose patients to increased risk of complications. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and non-alcoholic steatohepatitis (NASH) is the aggressive form of NAFLD. OBJECTIVE: The aim of this study is to determine the relationship between metabolic syndrome components and the risk of COVID-19. METHODS: We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED-CT), we identified adults with the diagnosis of metabolic syndrome and its individual components from 1999 to 2019. We included patients with the diagnosis of COVID-19 from December 2019 to May 2020. Comorbidities known to be associated with COVID-19 and metabolic syndrome such as obesity, diabetes mellitus, dyslipidemia, smoking, male gender, African American, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether metabolic syndrome or its individual components are independently associated with the risk of COVID-19. RESULTS: Out of 61.4 million active adult patients in the database, 8885 (0.01%) had documented COVID-19. The cumulative incidence of COVID-19 was higher if metabolic syndrome was the primary diagnosis (0.10% vs 0.01%, OR 7.00 [6.11-8.01]). The adjusted odds (aOR) of having COVID-19 was higher in patients if they were African Americans (aOR 7.45 [7.14-7.77]), hypertensive (aOR 2.53 [2.40-2.68]), obese (aOR 2.20 [2.10-2.32]), diabetic (aOR 1.41 [1.33-1.48]), hyperlipidemic (aOR 1.70 [1.56-1.74]), or diagnosed with NASH (aOR 4.93 [4.06-6.00]). There was a slight decrease in the adjusted odds of having COVID-19 in males as compared to females (aOR 0.88 [0.84-0.92]). CONCLUSION: The incidence of COVID-19 in patients with metabolic syndrome is high. Among all comorbid metabolic conditions, NASH had the strongest association with COVID-19.

FIB-4 Regression With Direct-Acting Antiviral Therapy in Patients With Hepatitis C Infection: A Safety-Net Hospital Experience.

Background: Liver fibrosis stage determines the risk of morbidity and mortality from chronic hepatitis C virus (HCV) infection. The majority of HCV-infected patients are underserved and have other comorbid conditions that lead to more progressive liver disease such as cirrhosis and hepatocellular carcinoma. Safety net hospitals are the prime location to treat these patients. Direct acting antiviral (DAA) agents are highly effective in virus eradication. Aim: We aimed to evaluate the effect of treatment with DAAs on FIB-4 index. Methods: We identified 343 patients who initiated HCV treatment with DAAs from 2016 to 2018 and achieved a sustained virologic response (SVR) in Metrohealth Medical Center, a safety net hospital system. We compared the severity of hepatic fibrosis before and 1 year after SVR was attained. We evaluated whether the presence of other comorbid conditions influenced liver fibrosis regression. All analyses were performed using SAS software. Results: There was a statistically significant drop in mean FIB-4 score from baseline to post-SVR (3.47 ± 2.84 vs. 2.28 ± 1.60, P < 0.001). One hundred seventeen patients had baseline FIB-4 scores ≥3.25, 56% had FIB-4 scores <3.25 after SVR. Alcohol use disorder was associated with a higher baseline FIB-4 score compared to low level drinking (3.85 ± 0.20 vs. 3.15 ± 0.16). These patients showed greater improvement in FIB-4 scores after treatment when compared to those without alcohol use disorder (1.44 ± 0.15 vs. 0.97 ± 0.13, P = 0.02). Conclusion: FIB-4 index is a useful non-invasive tool for monitoring fibrosis regression after antiviral therapy. Patients with a history of alcohol abuse had the greatest reduction in FIB-4 score post-SVR.