Showing papers in "Journal of Clinical Gastroenterology in 2021"

The Prevalence of Gastrointestinal Symptoms, Abnormal Liver Function, Digestive System Disease and Liver Disease in COVID-19 Infection: A Systematic Review and Meta-Analysis.

Abstract: BACKGROUND: The worldwide outbreak of COVID-19 infected millions of people. Some patients had gastrointestinal (GI) symptoms, abnormal liver function, digestive system disease and liver disease. AIM: To investigate the prevalence of GI symptoms, abnormal liver function, digestive system disease and liver disease in patients with COVID-19 by a systematic review and meta-analysis. METHODS: We searched PubMed, Ovid Embase, Medline, and 2 Chinese databases. Primary outcomes were the prevalence of GI symptoms, abnormal liver function, digestive system disease, and liver disease. Different studies were included in different subset analysis. These outcomes were estimated with proportions, odds ratio, 95% confidence interval (CI) and P-value by Stata SE 15.1. RESULTS: Thirty-one studies involving 4682 patients were included. The most significant GI symptoms were diarrhea (0.08, 95% CI: 0.06-0.11) and anorexia (0.17, 95% CI: 0.06-0.27). The most significant abnormal liver function was increased alanine aminotransferase (ALT) (0.25, 95% CI: 0.16-0.33). A total of 5% of the patients had digestive system disease (95% CI: 0.02-0.08). A total of 3% of the patients had liver disease (95% CI: 0.02-0.05). The prevalence of nausea and vomiting, diarrhea, abnormal liver function, digestive system disease, and liver disease was higher in Wuhan group. The prevalence of diarrhea was higher in non-China group. Patients in severe/intensive care unit group were more likely to have diarrhea, anorexia, abdominal pain increased aspartate aminotransferase, and increased ALT. CONCLUSION: The most significant GI symptoms were anorexia and diarrhea. The most significant abnormal liver function was increased ALT. Severe patients were more likely to have GI symptoms and abnormal liver function.

COVID-19 in Chronic Liver Disease and Liver Transplantation: A Clinical Review.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has brought challenges to clinicians caring for patients with chronic liver disease. In the past 6 months, COVID-19 has led to over 150,000 deaths in the United States and over 660,000 deaths around the world. Mounting evidence suggests that chronic liver diseases can have an adverse effect on the clinical outcomes of patients with COVID-19. We present a comprehensive review of the latest literature on preexisting liver diseases and its interrelationship with COVID-19 infection in cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, autoimmune hepatitis, and viral hepatitis B. As social distancing and telemedicine gain new footing, we synthesize recommendations from 3 major hepatology societies [American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL), and the Asian Pacific Association for the Study of Liver (APASL)] to present the best approaches for caring for patients with liver diseases as well as those requiring liver transplantation.

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as "bystander hepatitis," myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19-such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection.

Epidemiology of Autoimmune Hepatitis (AIH) in the United States Between 2014 and 2019: A Population-based National Study.

Abstract: BACKGROUND AND AIMS Autoimmune hepatitis (AIH) is a chronic, inflammatory disease of the liver with increasing prevalence. However, limited epidemiological data exist for the prevalence of AIH in the United States. We used a large database to describe the prevalence of AIH in the United States and the autoimmune diseases associated with it. APPROACH AND RESULTS Data was collected from a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated health care systems in the United States. We identified a cohort of patients with a diagnosis of AIH from April 2014 to April 2019 based on a Systemized Nomenclature of Medicine-Clinical Terms and calculated the prevalence of AIH. Of the 37,161,280 individuals active in the database from April 2014 to 2019, we identified 11,600 individuals with a diagnosis of AIH with an overall prevalence rate of 31.2/100,000. The prevalence of AIH was increased in females compared with males [odds ratio (OR)=3.21, P<0.0001], elderly (aged above 65 y) compared with adults (aged 18 to 65 y) and children (aged below 18 y) (OR=2.51, P<0.0001) and whites compared with African Americans, Asians, and Hispanics (OR=1.12, P<0.0001). Moreover, patients with AIH were more likely to have Sjogren syndrome, systemic lupus erythematosus, ulcerative colitis, celiac disease, rheumatoid arthritis, Crohn's disease, and autoimmune thyroiditis as compared with patients without AIH. CONCLUSIONS We found that the estimated prevalence of AIH in the United States is 31.2/100,000, which is comparable to the reported prevalence of AIH in Europe. We confirmed that AIH has a strong association with other autoimmune diseases studied in the literature.

Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

Abstract: GOALS We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI). BACKGROUND FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules. STUDY A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy). RESULTS Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT. CONCLUSIONS Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.

Alcohol-associated Cirrhosis and Alcoholic Hepatitis Hospitalization Trends in the United States

Abstract: GOALS The goals of this study were to evaluate trends in hospitalizations and in-hospital mortality among US adults with alcohol-associated cirrhosis and alcoholic hepatitis. BACKGROUND Alcohol-associated liver disease contributes to significant liver-related morbidity in the United States, among which inpatient care is a major driver of clinical and economic burden. METHODS Using the 2007-2014 National Inpatient Sample, alcohol-associated cirrhosis and alcoholic hepatitis hospitalizations were identified. Survey-weighted annual hospitalization trends were stratified by sex, race/ethnicity, and age and compared using χ2 and Student's t-test methods. Adjusted multivariate logistic regression models evaluated predictors of in-hospital mortality. RESULTS Among 159,973 alcohol-associated liver disease hospitalizations, 83.7% had a primary diagnosis of alcohol-associated cirrhosis and 18.4% had a primary diagnosis of alcoholic hepatitis. Sex-specific differences in hospitalizations emerged, with significantly higher hospitalization rates seen in males versus females among both alcoholic hepatitis [incidence rate ratio=3.71, 95% confidence interval (CI): 3.47-4.01, P<0.01] and alcohol-associated cirrhosis (incidence rate ratio=2.68, 95% CI: 2.21-3.71, P<0.01). Differences in hospitalization and mortality by ethnicity were observed for both alcohol-associated cirrhosis and alcoholic hepatitis. African Americans with alcohol-associated cirrhosis had significantly higher in-hospital mortality compared with non-Hispanic whites [odds ratio (OR)=1.13, 95% CI: 1.04-1.24, P<0.01], whereas Native Americans (OR=1.88, 95% CI: 1.06-3.34, P=0.030) and Asian/Pacific Islanders (OR=2.02, 95% CI: 1.00-4.06, P=0.048) with alcoholic hepatitis had significantly higher in-hospital mortality compared with non-Hispanic whites. CONCLUSIONS This study demonstrated increasing alcohol-associated cirrhosis and alcoholic hepatitis hospitalizations in the United States. The highest rates were observed in men and among Native American and Hispanic ethnic minorities. Significant ethnicity-specific disparities in mortality were observed.

Novel Bioenhanced Curcumin With Mesalamine for Induction of Clinical and Endoscopic Remission in Mild-to-Moderate Ulcerative Colitis: A Randomized Double-Blind Placebo-controlled Pilot Study.

Abstract: BACKGROUND AND AIMS The aim of this study was to assess the efficacy and safety of a novel, hydrophilic, bioenhanced curcumin (BEC) as add-on therapy in inducing clinical and endoscopic remission in mild to moderately active ulcerative colitis (UC). DESIGN Mild to moderately active UC patients (partial Mayo score 2 to 6 with endoscopic Mayo score >1) on standard dose of mesalamine were randomized to either 50 mg twice daily BEC or an identical placebo. Clinical response (≥2 reduction of partial Mayo score), clinical remission (partial Mayo score ≤1), and endoscopic remission (endoscopic Mayo score of ≤1) were evaluated at 6 weeks and 3 months. Responders were followed-up at 6 and 12 months for assessing maintenance of remission. RESULTS Sixty-nine patients were randomly assigned to BEC (n=34) and placebo (n=35). At 6 weeks, clinical and endoscopic remission occurred in 44.1% (15/34) and 35.3% (14/34) patients, respectively, compared with none in the placebo group (P<0.01). Clinical response was also significantly higher in the BEC group (18/34, 52.9%) compared with placebo (5/35, 14.3%) (P=0.001). The clinical remission, clinical response, and endoscopic remission rates at 3 months were 55.9% (19/34), 58.8% (20/34), 44% (16/34) and 5.7% (2/35), 28.6% (10/35), 5.7% (2/35) in BEC and placebo groups, respectively. At 6 and 12 months, 95% (18/19) and 84% (16/19) of the responders to BEC maintained clinical remission. None of the responders to placebo maintained clinical remission at 6 months. BEC appeared safe with no significant side effects. CONCLUSION A low-dose BEC as add-on therapy was superior to placebo in inducing sustained clinical and endoscopic remission in patients with mild-to-moderately active UC on maximal dose of mesalamine (ClinicalTrials.gov: NCT02683733).

A Network Meta-Analysis of Randomized Controlled Trials on the Treatment of Eosinophilic Esophagitis in Adults and Children.

Abstract: Background Network meta-analysis is used as a data synthesizer, incorporating direct and indirect evidence about treatments in a series of randomized control trials. Objective To evaluate the comparative efficacy of various treatments for eosinophilic esophagitis (EoE). Methods We performed a network meta-analysis to combine direct and indirect data to investigate the efficiency of drug therapies, which were evaluated in relevant randomized control trials for EoE. Results Seventeen eligible studies (14 two-arm and 3 multiple-arm) were introduced to the meta-analysis. A total of 1011 patients were included, in whom 15 therapeutic interventions were used, namely: (1) budesonide oral suspension, (2) budesonide 1 mg orodispersible tablet twice daily, (3) budesonide 2 mg orodispersible tablet twice daily, (4) esomeprazole, (5) fluticasone, (6) nebulized steroid, (7) placebo, (8) prednisone, (9) anti-IL-5-mab (mepolizumab), (10) anti-IL-5-mab [reslizumab(1), ie, 1 mg/kg], (11) anti-IL-5-mab [reslizumab(2), ie, 2 mg/kg], (12) anti-IL-5-mab [reslizumab(3), ie, 3 mg/kg], (13) anti-IL-13-mab (QAX 576), (14) anti-IL-13-mab [RCP 4046 (180)], and (15) anti-IL-13-mab [RCP 4046 (360)]. Budesonide 1 mg orodispersible tablet twice daily showed the highest efficacy (SUCRA 0.91), whereas placebo was the least effective. In adult patients budesonide 1 mg orodispersible tablet twice daily remained the optimal treatment approach, whereas the corresponding therapeutic approach in pediatric patients was fluticasone. Conclusions This meta-analysis showed that budesonide 1 mg orodispersible tablet twice daily was the best treatment for EoE, as it was the most effective. This treatment remained the optimal approach in adult patients, whereas fluticasone was the best treatment in pediatric patients.

Liver Stiffness Measured by Either Magnetic Resonance or Transient Elastography Is Associated With Liver Fibrosis and Is an Independent Predictor of Outcomes Among Patients With Primary Biliary Cholangitis.

Abstract: Goals We aimed to describe the diagnostic and prognostic performance of transient elastography (TE) and magnetic resonance elastography (MRE) in patients with primary biliary cholangitis (PBC). Background The diagnostic performance of TE and MRE in detecting advanced fibrosis in PBC and in predicting outcomes independent of existing serologic prognostic markers is incompletely understood. Materials and methods Five hundred thirty-eight consecutive patients with PBC at 3 centers with liver stiffness (LS) measurements by TE (n=286) or MRE (n=332) were reviewed. LS cutoffs for predicting fibrosis stages were determined by receiver operating characteristic curves among those with a liver biopsy (TE, n=63; MRE, n=98). Cox proportional hazard regression modeling was used to identify associations between covariates and hepatic decompensation. Results The optimal LS thresholds for predicting histologic stage F4 were 14.40 kPa (area under the curve=0.94) for TE and 4.60 kPa (area under the curve=0.82) for MRE. Both TE and MRE outperformed biochemical markers for the prediction of histologic advanced fibrosis. Optimal LS thresholds to predict hepatic decompensation were 10.20 kPa on TE and 4.30 kPa on MRE. LS by TE and MRE (respectively) remained predictors of hepatic decompensation after adjusting for ursodeoxycholic acid responsiveness [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.24 and HR, 1.68; 95% CI, 1.28-2.19] and the GLOBE score (HR, 1.13; 95% CI, 1.07-1.19 and HR, 2.09; 95% CI, 1.57-2.78). Conclusion LS measurement with either TE or MRE can accurately detect advanced fibrosis and offers additional prognostic value beyond existing serologic predictive tools.

Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults: A Meta-Analysis of Randomized Placebo-Controlled Trials.

Abstract: OBJECTIVE This meta-analysis aims to combine the latest research evidence to assess the effect of probiotics on preventing antibiotic-associated diarrhea (AAD) in adults. METHODS PubMed, Cochrane Library, EMBASE, and Web of Science were searched for randomized placebo-controlled trials on probiotics preventing AAD. A random or fixed effect model was used to combine the incidence of AAD (primary outcome) and the adverse event rates. The authors performed subgroup analyses to explore the effects of different participants population, probiotics species, and dosage. RESULTS Thirty-six studies were included with 9312 participants. Probiotics reduced the incidence of AAD by 38% (pooled relative risk, 0.62; 95% confidence interval, 0.51-0.74). The protective effect of probiotics was still significant when grouped by reasons for antibiotics treatment, probiotic duration, probiotic dosage, and time from antibiotic to probiotic. However, there were no statistically significant increased adverse events in the probiotics group (relative risk, 1.00; 95% confidence interval, 0.87-1.14). CONCLUSIONS This updated meta-analysis suggested that using probiotics as early as possible during antibiotic therapy has a positive and safe effect on preventing AAD in adults. Further studies should focus on the optimal dosage and duration of probiotics to develop a specific recommendation.

Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg)

Abstract: Background Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. Aim The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". Methods European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. Results Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. Conclusion The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

Association Between Helicobacter pylori Colonization and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Abstract: Background Various observational studies have examined a potential relationship between Helicobacter pylori colonization and inflammatory bowel diseases (IBDs); however, results are inconclusive. This systematic review evaluates articles reporting an association between human H. pylori colonization and IBD. Methods A systematic search of studies was conducted to evaluate a possible relationship between H. pylori colonization and IBD. Seven databases and different types of gray literature were searched. After screening for relevant articles, selection and data extraction were done. After that, the data were analyzed, and pooled odds ratios (ORs) were calculated, using meta-analysis. Heterogeneity, sensitivity, and subgroups analyses were conducted. Funnel plots followed by Begg and Egger tests were done to assess the publication bias. Results Among 58 studies, including 13,549 patients with IBD and 506,554 controls, the prevalence of H. pylori colonization was 22.74% and 36.30%, respectively. A significant negative association was observed between H. pylori colonization and IBD (pooled OR: 0.45, 95% confidence interval 0.39-0.53, P≤0.001). The random-effect model showed significant statistical heterogeneity in the included studies (I=79%). No publication bias was observed. Among subgroups, ORs were notably different when the data were stratified by the age difference between patient and control group, and by study regions and/or continent. Finally, the meta-regression analysis showed significant results, in terms of the age difference and region variables. Conclusions In this meta-analysis, all statistical data support the theory that H. pylori has a protective role in IBD. However, more primary studies using proper methodology are needed to confirm this association.

Efficacy and Safety of Statin for Hepatocellular Carcinoma Prevention Among Chronic Liver Disease Patients: A Systematic Review and Meta-analysis.

Abstract: INTRODUCTION AND AIM Hepatocellular carcinoma (HCC) is a deadly complication among patients with chronic liver disease (CLD). Controversies on the efficacy and safety of statin to prevent HCC among patients with CLD remain despite the growing evidences. We aim to investigate the efficacy and safety of using statin for HCC prevention among adult with CLD. METHODS We performed a systematic search of 4 electronic databases (PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrial.gov) up to April 15, 2020. We selected all types of studies evaluating the statin use and the risk of HCC among CLD patients, regardless of language, region, publication date, or status. The primary endpoint was the pooled risk of HCC. The secondary endpoint was the risk of statin-associated myopathy. RESULT From 583 citations, we included a total of 13 studies (1,742,260 subjects, 7 types of statins), fulfilling the inclusion criteria, evaluating efficacy and safety of statin in CLD patients for HCC prevention. All studies were observational (2 nested case-control studies, 11 cohort studies), and no randomised trial was identified. We found that statin user has a lower pooled risk of HCC development (hazard ratio=0.57, 95% confidence interval: 0.52-0.62, I2=42%). HCC reduction was consistent among statin users in cirrhosis, hepatitis B virus, and hepatitis C virus infections. The risk of statin-associated myopathy was similar between statin user and nonuser (hazard ratio=1.07, 95% confidence interval=0.91-1.27). CONCLUSION Statin use was safe and associated with a lower pooled risk of HCC development among adults with CLD. Given the bias with observation studies, prospective randomised trial is needed to confirm this finding.

Acupuncture and Related Therapies for the Treatment of Gastrointestinal Diseases.

Abstract: Gastrointestinal diseases are very common worldwide. Patients with gastroesophageal reflux disease, functional dyspepsia, irritable bowel syndrome, and inflammatory bowel diseases frequently recur to complementary medicine, including acupuncture, likely because of the recurrence of symptoms and the sometimes lack of efficacy of conventional treatments. Acupuncture is a medical practice used in Asian country with benefits for thousands years. In the last decades, growing attention has been given to acupuncture also in Western countries and many studies have investigated the role of acupuncture in gastroenterology. This review provided an overview of the effectiveness and potential mechanisms of action of acupuncture for the treatment of gastrointestinal diseases.

Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.

Abstract: BACKGROUND AND GOALS Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort. METHODS A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month. RESULTS Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy. CONCLUSIONS Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.

Efficacy and Safety of Monoclonal Antibodies Against Clostridioides difficile Toxins for Prevention of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

Abstract: BACKGROUND Clostridioides difficile infection is one of the most common health care-associated infections. To reduce the recurrent Clostridioides difficile infection (rCDI), monoclonal antibodies against Clostridioides difficile toxin A (actoxumab) and toxin B (bezlotoxumab) were developed. In the present study, we performed a systematic review and meta-analysis to assess their efficacy and safety. MATERIALS AND METHODS An electronic database was searched for relevant randomized controlled trials assessing bezlotoxumab and/or actoxumab. Outcomes included rate of rCDI and adverse events including cardiovascular and gastrointestinal events. RESULTS Four randomized controlled trials comparing antitoxin antibodies (n=1916) versus placebo (n=889) were identified. rCDI was significantly reduced by bezlotoxumab plus actoxumab (risk ratio=0.54, 95% confidence interval=0.41-0.70, P<0.001) and bezlotoxumab monotherapy (risk ratio=0.62, 95% confidence interval=0.51-0.76, P<0.001) compared with placebo. Subgroup analysis showed that bezlotoxumab plus actoxumab was remarkably preventive for patients with the following high-risk features: inpatients, vancomycin treatment, and BI/NAP/027 strain. Regarding safety, there was no difference in cardiovascular and gastrointestinal events as well as all-cause mortality between bezlotoxumab-treated patients and placebo. CONCLUSIONS The results of our meta-analysis demonstrated the effectiveness and safety of bezlotoxumab for the prevention of rCDI. Bezlotoxumab may be a good therapeutic option for severe C. difficile infection rather than mild cases.

Real-world Comorbidity Burden, Health Care Utilization, and Costs of Nonalcoholic Steatohepatitis Patients With Advanced Liver Diseases.

Abstract: GOALS This study evaluates the real-world comorbidity burden, health care resource utilization (HRU), and costs among nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) patients with advanced liver diseases [compensated cirrhosis (CC), decompensated cirrhosis (DCC), liver transplantation (LT), hepatocellular carcinoma (HCC)] BACKGROUND NAFLD/NASH is a leading cause of liver diseases MATERIALS AND METHODS Adult NAFLD/NASH patients were identified retrospectively from MarketScan Commercial claims (2006-2016) Following initial NAFLD/NASH diagnosis, advanced liver diseases were identified using the first diagnosis as their index date Mean annual all-cause HRU and costs (2016 USD) were reported Adjusted costs were estimated through generalized linear models Cumulative costs were illustrated for patient subsets with variable follow-up for each stage RESULTS Within the database, 485,774 NAFLD/NASH patients met eligibility criteria Of these, 934% (453,564) were NAFLD/NASH patients without advanced liver diseases, 16% (7665) with CC, 33% (15,833) with DCC, 01% (696) with LT, and 01% (428) with HCC Comorbidity burden was high and increased as patients progressed through liver disease severity stages Compared with NAFLD/NASH without advanced liver diseases (adjusted costs: $23,860), the annual cost of CC, DCC, LT, and HCC were 122, 564, 827, and 409 times higher [adjusted costs: $29,078, $134,448, $197,392, and $97,563 (P<00001)] Inpatient admissions significantly drove increasing HRU CONCLUSION Study findings suggest the need for early identification and effective management of NAFLD/NASH patients to minimize comorbidity burden, HRU, and costs in the privately insured US population

Nausea and Vomiting in 2021: A Comprehensive Update.

Abstract: Goal A comprehensive review of treatments for nausea and vomiting (N/V). Background N/V are common symptoms encountered in medicine. While most cases of acute N/V related to a specific cause can be straightforward to manage, other cases of acute N/V such as chemotherapy-induced N/V and especially chronic unexplained N/V can be difficult to control, leading to a significant decline in the patient's quality of life and increased cost of medical care from repeated hospitalizations. Study Traditional management has relied on pharmacotherapy which may be inadequate in a certain proportion of these patients. Many of the medications used in the management of N/V have significant side effect profiles making the need for new and improved interventions of great importance. Results This review covers a broad review of the pathophysiology of N/V, pharmacotherapy, including safety concerns and controversies with established pharmaceuticals, newer immunotherapies, bioelectrical neuromodulation (including gastric electrical stimulation), behavioral and surgical therapies, and complementary medicine. Conclusion On the basis of emerging understandings of the pathophysiology of N/V, improved therapies are becoming available.

Gastrointestinal Symptoms Predict the Outcomes From COVID-19 Infection.

Abstract: Coronavirus disease 2019 (COVID-19) has taken hundreds of thousands of lives globally. Besides the respiratory tract, the virus can affect the gastrointestinal (GI) tract. Data regarding the significance of GI symptoms in the COVID-19 course are limited. In this largest US study to date, the authors reviewed electronic encounters of 1003 consecutive patients who were tested positive for the virus between March 12 and April 3, 2020. Initial GI symptoms were present in up to 22.4% of patients and were associated with worse outcomes after adjustment for demographics, comorbidities, and other clinical symptoms. COVID-19 with GI involvement may define a more severe phenotype.

Low Risk of Progression of Barrett's Esophagus to Neoplasia in Women.

Abstract: BACKGROUND AND AIMS Men are at a higher risk for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression. METHODS We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables. RESULTS Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002). CONCLUSIONS In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.

Endoscopic Ultrasound Guided Gastroenterostomy: What Is the Learning Curve?

Abstract: INTRODUCTION Endoscopic ultrasound guided gastroenterostomy (EUS-GE) is a minimally invasive option for gastric outlet obstruction. It requires skills in endoscopic ultrasound, fluoroscopy, and lumen-apposing metal stent deployment. The aim of this study was to determine the learning curve for EUS-GE. METHODS Consecutive patients undergoing EUS-GE by a single operator were included from a prospective registry over 3 years. Demographics, procedure info, postprocedure follow-up data, and adverse events were collected. Nonlinear regression and cumulative sum analyses were conducted for the learning curve. Clinical success was defined as tolerating a diet postprocedure. RESULTS Twenty-three patients were included (39% male, mean age 65.8 y). Technical success was achieved in 22 (96%) patients. Clinical success was achieved in 21/22 (95%) patients. Average follow-up time 10.8 months (9.1 SD). Five patients had minor postprocedure complications; 1 patient had a periprocedural esophageal tear treated with clips. Four patients required repeat intervention for stent revision or removal if no longer needed.Median procedure time was 88 minutes (range: 45 to 140 min). Cumulative sum chart shows 88-minute procedure time was achieved at the seventh procedure indicating efficiency. Even with bridging of a misdeployed lumen-apposing metal stent, the procedure duration further reduced with consequent procedures indicating continued improvement with experience (nonlinear regression P<0.0001). CONCLUSIONS Endoscopists experienced in EUS-GE achieve a reduction in procedure time over successive cases, with efficiency reached at 88 minutes and a learning rate of 7 cases. Misdeployed stents that require bridging add to the procedure time even after competency is achieved but do not affect the overall learning curve trend.

Risk of Severe COVID-19 Increased by Metabolic Dysfunction-associated Fatty Liver Disease: A Meta-analysis.

Abstract: BACKGROUND: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronavirus disease-2019 (COVID-19) patients and whether it affects the outcomes of COVID-19 requires investigation. GOALS: The aim was to determine the prevalence of MAFLD among COVID-19 patients and its influence on the outcomes of COVID-19 by meta-analysis. METHODS: Our study protocol has been registered on PROSPERO (CRD42021242243). The studies published on PubMed, Embase, Cochrane Library, and Web of Science before March 11, 2021 were screened. The Newcastle-Ottawa scale (NOS) and Agency for Healthcare Research and Quality scale were used to assess the quality of the studies. Pooled analysis was conducted using the software RevMan version 5.3 and Stata version 15.0 SE. The stability of the results was assessed by sensitivity analysis. Publication bias was evaluated using funnel plots, Egger test, and trim-and-fill analysis. RESULTS: Seven studies covering 2141 COVID-19 patients were included. It was confirmed that MAFLD increased the risk of severe COVID-19 (odds ratios: 1.80, 95% confidence interval: 1.53-2.13, P<0.00001). No association was found between the presence of MAFLD and the occurrence of COVID-19 death. The pooled prevalence of MAFLD among COVID-19 patients was 36% (95% confidence interval: 0.23-0.49, P<0.00001). Sensitivity analysis confirmed that the initial results were stable. CONCLUSIONS: MAFLD can increase the incidence of severe COVID-19, but the correlation between MAFLD and COVID-19 death has not been confirmed. Further investigation is needed to explore the possible mechanism of this association. Since MAFLD is common among patients infected with SARS-CoV-2, more care should be given to COVID-19 patients with underlying MAFLD.

Use of Small Bowel Ultrasound to Predict Response to Infliximab Induction in Pediatric Crohn's Disease.

Abstract: GOAL The goal of this study was to explore the utility of small bowel ultrasound (SBUS) as a noninvasive tool to assess induction response to infliximab (IFX) in pediatric Crohn's disease (CD). BACKGROUND Inflammatory bowel disease management has shifted to a treat-to-target and tight control strategy utilizing noninvasive serum and fecal markers to monitor disease activity in response to therapy. Bowel wall changes as seen on cross-sectional imaging may be a more accurate marker of treatment success. MATERIALS AND METHODS Pediatric patients with CD with small bowel involvement initiating IFX were prospectively enrolled. Clinical activity, biomarkers, and SBUS findings were evaluated at baseline (T0) and postinduction at week 14 (T1). The primary outcome was to describe the changes in SBUS parameters pre and post IFX induction and how they associate with clinical and biomarker response. Descriptive statistics summarized the data and univariate analysis tested associations. RESULTS All 13 CD patients achieved steroid-free clinical remission (P<0.001) and a decrease in C-reactive protein (P=0.01) postinduction. Bowel wall hyperemia (BWH) (P=0.01) and bowel segment length involved (P=0.07) decreased postinduction. Decrease in fecal calprotectin at T1 moderately correlated with a decrease in bowel segment length (r=0.57; P=0.04). No correlation was seen with a change in bowel wall thickness or BWH postinduction. CONCLUSIONS Our pilot study suggests that SBUS is a feasible, noninvasive tool to measure early treatment response to IFX. BWH, not bowel wall thickness, is the first parameter to change. Larger longitudinal studies are warranted to validate the utility of SBUS as part of a disease monitoring strategy.

Safety and Efficacy of Biological Therapy in Chronic Antibiotic Refractory Pouchitis: A Systematic Review With Meta-analysis.

Abstract: Background Pouchitis is the most common long-term complication after ileal pouch-anal anastomosis in patients with ulcerative colitis. Those with ≥3 episodes of pouchitis/year and symptoms despite antibiotics are considered to have chronic antibiotic refractory pouchitis (CARP). While several agents including probiotics, steroids and immunomodulators have been used, treatment of CARP remains challenging. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of various biological agents in treatment of CARP. Methods Multiple databases were searched through June 2020 for studies that reported the efficacy and safety of biological therapy including antitumor necrosis factor-alpha agents [infliximab (IFX) and adalimumab (ADA)], vedolizumab (VDZ), and ustekinumab in CARP. We excluded studies on Crohn's like and/or other inflammatory complications of the pouch. Meta-analysis was performed to calculate pooled rates of clinical as well as endoscopic improvement and remission. Results We included 15 studies with 311 patients in our final analysis. Ninety-two patients were treated with IFX, 42 with ADA, 144 with VDZ and 33 with ustekinumab. Pooled rate of clinical improvement was 71.4%, 58.2%, 47.9% and clinical remission was 65.7%, 31%, 47.4% with IFX, ADA, and VDZ, respectively. Pooled rate of endoscopic improvement was achieved in 61.2% patients treated with VDZ while endoscopic remission was achieved in 70.3% patients treated with IFX. Adverse events were reported in 3.9% patients. Conclusion Biologic therapy is safe and effective in the treatment of CARP.

Per Oral Endoscopic Myotomy for Zenker's Diverticulum: A Novel and Superior Technique Compared With Septotomy?

Abstract: Introduction Endoscopic management of Zenker diverticuli (ZD) has traditionally been via septotomy technique. The recent development of tunneling technique has shown to be both efficacious and safe. The aim of this study is to evaluate the tunneling technique using per oral endoscopic myotomy (Z-POEM) versus septotomy. Methods Patients who underwent endoscopic management of ZD either by Z-POEM or septotomy from March 2017 until November 2020 from 9 international academic centers were included. Demographics, clinical data preprocedure and postprocedure, procedure time, adverse events, and hospital length of stay were analyzed. Results A total of 101 patients (mean age 74.9 y old, 55.4% male) were included: septotomy (n=49), Z-POEM (n=52). Preprocedure Functional Oral Intake Scale score and Eckardt score was 5.3 and 5.4 for the septotomy group and 5.9 and 5.15 for the Z-POEM group. Technical success was achieved in 98% of the Z-POEM group and 100% of the septotomy group. Clinical success was achieved in 84% and 92% in the septotomy versus Z-POEM groups. Adverse events occurred in 30.6% (n=15) in septotomy group versus 9.6% (n=5) in the Z-POEM group (P=0.017). Reintervention for ongoing symptoms occurred in 7 patients in the septotomy group and 3 patients in the Z-POEM group. Mean hospital length of stay was shorter for the Z-POEM group, at 1.5 versus 1.9 days. Conclusions A tunneling technique via the Z-POEM procedure is an efficacious and safe endoscopic treatment for ZD. Z-POEM is a safer procedure with a statistically significant reduction in adverse events compared with traditional septotomy technique.

Novel Orally Administered Recombinant Anti-TNF Alpha Fusion Protein for the Treatment of Ulcerative Colitis: Results From a Phase 2a Clinical Trial.

Abstract: BACKGROUND AND OBJECTIVE OPRX-106 is an orally administered BY2 plant cell-expressing recombinant TNF fusion protein (TNFR). Oral administration of OPRX-106 was shown to be safe and effective in inducing favorable anti-inflammatory immune modulation in humans. The current study was aimed at determining the safety and efficacy of OPRX-106 in patients with ulcerative colitis (UC). METHODS Twenty-five patients with active mild-to-moderate UC were enrolled in an open-label trial. Patients were randomized to receive 2 or 8 mg of OPRX-106 administered orally once daily, for 8 weeks. Patients were monitored for safety and efficacy including clinical response or clinical remission, based on the Mayo score. The histopathological improvement in Geboes score, calprotectin level and hs-CRP, and exploratory immune parameters by means of fluorescence-activated cell sorting and cytokine levels were monitored. RESULTS Oral administration of OPRX-106 was found to be safe and well tolerated without absorption into the circulation. Out of 24 patients, 18 completed the trial. The analysis of the patients completing treatment demonstrated clinical efficacy as measured by clinical response or remission in 67% and 28%, respectively. Reduction in calprotectin levels and improved Geboes score were noted in the majority of the treated patients. The beneficial clinical effect was associated with an increase in a CD4+CD25+FoxP3 subset of suppressor lymphocytes and a reduction in interleukin 6 and interferon gamma serum levels. CONCLUSIONS Oral administration of the nonabsorbable OPRX-106 is safe and effective in mild-to-moderate UC, and not associated with immune suppression, while inducing favorable anti-inflammatory immune modulation.

Impact of COVID-19 on Individuals With Irritable Bowel Syndrome and Comorbid Anxiety and/or Depression.

Abstract: Goals The goal of this study was to describe the influence of the COVID-19 pandemic on ability to engage in activities and the influence on psychological distress and gastrointestinal symptoms among individuals with irritable bowel syndrome (IBS) and comorbid anxiety and/or depression. Background Individuals with IBS and comorbid anxiety and/or depression report increased symptoms and decreased quality of life compared with individuals with IBS alone. The current COVID-19 pandemic has the potential to further influence symptoms among individuals with IBS and comorbid anxiety and/or depression. Study Individuals who met the Rome-IV IBS criteria and reported mild to severe anxiety and/or depression were included. Participants completed an online survey with questions about anxiety, depression, impact of COVID on activities and symptoms, and demographics. Results Fifty-five individuals participated in the study. The COVID-19 pandemic most commonly influenced their ability to spend time with friends and family, shop for certain types of food, and access health care. Participants also reported increased stress (92%), anxiety (81%), and depressive symptoms (67%). Finally, around half the sample reported increases in abdominal pain (48%), diarrhea (45%), or constipation (44%). Conclusions The COVID-19 pandemic is related to self-reported increases in psychological distress and gastrointestinal symptoms among individuals with IBS and comorbid anxiety and/or depression. Additional research is needed to intervene on these symptoms.

Balloon-occluded Retrograde Transvenous Obliteration Versus Transjugular Intrahepatic Portosystemic Shunt for Gastric Varices: A Meta-Analysis.

Abstract: INTRODUCTION Balloon-occluded retrograde transvenous obliteration (BRTO) and transjugular intrahepatic portosystemic shunt (TIPS) are well-validated techniques in the management of portal hypertensive gastric variceal bleeding when medical management alone is not sufficient. However, despite their effectiveness, the adverse effects from both procedures make each technique more suitable to different cohorts of patient's depending on presence or lack of certain comorbidities. This study aims to compare clinical outcomes of patients who have undergone both procedures for portal hypertensive gastric variceal bleeding. MATERIALS AND METHODS We conducted a search of electronic databases from their establishment to April 2019. The goal was to compare the efficacy of BRTO and TIPS in preventing variceal rebleeding and the risk of adverse events such as ascites and hepatic encephalopathy. Predictors of overall survival and rebleeding were also analyzed. Meta-analysis was performed with STATA 15.1. RESULTS Five randomized controlled trials and retrospective cohort studies were included in our meta-analysis. The number of patients who underwent BRTO and TIPS were 308 and 127, respectively. BRTO and TIPS have similar technical success rates (91.4% vs. 89.7%, P=0.995) and immediate bleeding control rates (97.7% vs. 95.9%, P=0.836). However, compared with TIPS, BRTO has lower likelihood of future cumulative rebleeding (10.6% vs. 18.7%, P=0.027) and hepatic encephalopathy (0.00% vs. 23.1%, P<0.001) but is more likely to aggravate ascites (22.4% vs. 4.3%, P=0.009). Serum albumin level and presence of hepatocellular carcinoma are both independent predictors of increased likelihood of rebleeding and overall survival (P<0.001). CONCLUSIONS Both BRTO and TIPS are safe and effective interventions in the management algorithm of portal hypertensive gastric variceal bleeding. Although BRTO may be more effective at the prevention of future variceal rebleeding, the choice of BRTO versus TIPS should be tailored according to patient's comorbidities.

Altered Expression of the Epithelial Mucin MUC1 Accompanies Endoscopic Recurrence of Postoperative Crohn's Disease.

Abstract: BACKGROUND MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn's disease (CD) recurrence and could be considered an additional biomarker of recurrence severity. METHODS We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1. RESULTS A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P<0.0001) and hypoglycosylated/abnormal (P<0.0001) forms in patients with severe endoscopic CD recurrence (i3+i4), ileal score i2, compared with patients in endoscopic remission (i0+i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score. CONCLUSIONS MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.

Pancreatic Fungal Infection in Patients With Necrotizing Pancreatitis: A Systematic Review and Meta-analysis.

Abstract: GOAL The goal of this study was to study the incidence of fungal infection in necrotizing pancreatitis (NP) and its impact on mortality. BACKGROUND Infected pancreatic necrosis is a major contributor to morbidity and mortality in patients with NP. While pancreatic fungal infection (PFI) has frequently been identified in patients with NP, its effect on the clinical outcomes is unclear. MATERIALS AND METHODS A literature search was performed in Medline (Ovid), Embase (Ovid), and the Cochrane library. All prospective and retrospective studies that examined the incidence of fungal infection in NP with subgroup mortality data were included. For fungal infection of NP, studies with fungal isolation from pancreatic necrotic tissue were included. Newcastle Ottawa Scale and Joanna Briggs Institute's critical appraisal tool were used for bias assessment. RESULTS Twenty-two studies comprising 2151 subjects with NP were included for the quantitative analysis. The mean incidence of fungal infection was 26.6% (572/2151). In-hospital mortality in the pooled sample of NP patients with PFI (N=572) was significantly higher [odds ratio (OR)=3.95, 95% confidence interval (CI): 2.6-5.8] than those without PFI. In a separate analysis of 7 studies, the mean difference in the length of stay between those with and without fungal infection was 22.99 days (95% CI: 14.67-31.3). The rate of intensive care unit admission (OR=3.95; 95% CI: 2.6-5.8), use of prophylactic antibacterials (OR=2.76; 95% CI: 1.31-5.81) and duration of antibacterial therapy (mean difference=8.71 d; 95% CI: 1.33-16.09) were all significantly higher in patients with PFI. Moderate heterogeneity was identified among the studies on estimating OR for mortality (I2=43%) between the 2 groups. CONCLUSIONS PFI is common in patients with NP and is associated with increased mortality, intensive care unit admission rate, and length of stay. Further prospective studies are needed to better understand the pathophysiology of PFIs and to determine the role for preemptive therapeutic strategies, such as prophylactic antifungal therapy.