The 50 most-cited articles in The American Journal of Gastroenterology, 2021

Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that…

Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. CRC screening efforts are directed toward removal of adenomas and sessile serrated lesions and detection of early-stage CRC. The purpose of this article is to update the 2009 American College of Gastroenterology CRC screening guidelines. The guideline is framed around several key questions. We conducted a comprehensive literature search to include studies through October 2020. The inclusion criteria were studies of any design with men and women age 40 years and older. Detailed recommendations for CRC screening in average-risk individuals and those with a family history of CRC are discussed. We also provide recommendations on the role of aspirin for chemoprevention, quality indicators for colonoscopy, approaches to organized CRC screening and improving adherence to CRC screening. CRC screening must be optimized to allow effective and sustained reduction of CRC incidence and mortality. This can be accomplished by achieving high rates of adherence, quality monitoring and improvement,…

We performed systematic reviews addressing predefined clinical questions to develop recommendations with the GRADE approach regarding management of patients with overt upper gastrointestinal bleeding. We suggest risk assessment in the emergency department to identify very-low-risk patients (e.g., Glasgow-Blatchford score = 0-1) who may be discharged with outpatient follow-up. For patients hospitalized with upper gastrointestinal bleeding, we suggest red blood cell transfusion at a threshold of 7 g/dL. Erythromycin infusion is suggested before endoscopy, and endoscopy is suggested within 24 hours after presentation. Endoscopic therapy is recommended for ulcers with active spurting or oozing and for nonbleeding visible vessels. Endoscopic therapy with bipolar electrocoagulation, heater probe, and absolute ethanol injection is recommended, and low- to very-low-quality evidence also supports clips, argon plasma coagulation, and soft monopolar electrocoagulation; hemostatic powder spray TC-325 is suggested for actively bleeding ulcers and over-the-scope clips for recurrent ulcer bleeding…

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.

Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver…

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1-10 (1 = strongly disagree and 10 = strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous. During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new…

INTRODUCTION: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. METHODS: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. RESULTS: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.

Benign anorectal disorders of structure and function are common in clinical practice. These guidelines summarize the preferred approach to the evaluation and management of defecation disorders, proctalgia syndromes, hemorrhoids, anal fissures, and fecal incontinence in adults and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations Assessment, Development and Evaluation process. When the evidence was not appropriate for Grading of Recommendations Assessment, Development and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0). METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0. RESULTS: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these…

INTRODUCTION: Incidence of colorectal cancer (CRC) in young adults has been increasing in recent decades in many countries for still widely unclear reasons. Suspected candidates include increasing prevalence of overweight and obesity, but specific evidence on their role for early-onset CRC (EOCRC) is sparse. We conducted a systematic review and meta-analysis to summarize available evidence on the association of body mass index (BMI) with EOCRC. METHODS: We systematically searched PubMed, EMBASE, and Web of Science up to February 2021 for studies that evaluated the association of BMI (before diagnosis but not near diagnosis) with CRC risk and reported specific results for EOCRC. Results from studies with similar BMI groupings were summarized in meta-analyses using random-effects models. RESULTS: Twelve studies were eligible and included. Results of 6 studies were pooled in meta-analyses, which yielded a higher risk of EOCRC for overweight and obesity (BMI ≥25 kg/m2) compared with normal weight (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.68). An increasing risk with…

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age…

INTRODUCTION: Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations. METHODS: We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor). RESULTS: Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes,…

INTRODUCTION: The safety of Helicobacter pylori eradication treatments and to what extent adverse events (AEs) influence therapeutic compliance in clinical practice are hardly known. Our aim was to assess the frequency, type, intensity, and duration of AEs, and their impact on compliance, for the most frequently used treatments in the "European Registry on Helicobacter pylori management." METHODS: Systematic prospective noninterventional registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H. pylori infection in routine clinical practice. All prescribed eradication treatments and their corresponding safety profile were recorded. AEs were classified depending on the intensity of symptoms as mild/moderate/severe and as serious AEs. All data were subject to quality control. RESULTS: The different treatments prescribed to 22,492 patients caused at least 1 AE in 23% of the cases; the classic bismuth-based quadruple therapy was the worst tolerated (37% of AEs). Taste disturbance (7%), diarrhea (7%), nausea (6%), and…

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years,…

INTRODUCTION: Frailty is a predictor of morbidity and mortality in cirrhosis. Although evidence for prehabilitation is promising, the data for liver transplant (LT) candidates are limited. The primary aim of this study was to evaluate the effect of a novel prehabilitation strategy on changes in frailty metrics and survival in LT candidates. The secondary aim was to determine liver-related and extrahepatic conditions associated with frailty. METHODS: In this ambispective cohort study, all patients underwent frailty assessment using the liver frailty index (LFI), 6-minute walk test, and gait speed test performed by a dedicated physical therapist. Home-based exercise prescription was individualized to each patient's baseline physical fitness. RESULTS: We included 517 patients (59% men, median age 61 years, and a model for end-stage liver disease score of 12) evaluated during 936 PT visits. Frailty metrics were affected by age, sex, and liver-related parameters, but not by model for end-stage liver disease. Patients with nonalcoholic fatty liver disease and alcohol-related cirrhosis had…

INTRODUCTION: Patients with immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD) on immunosuppressive and biologic therapies were largely excluded from severe acute respiratory syndrome coronavirus-2 messenger RNA vaccine trials. METHODS: We evaluated adverse events (AE) after messenger RNA vaccination in 246 adults with IBD participating in a longitudinal vaccine registry. RESULTS: In general, AE frequency was similar to that reported in the general population. AEs were more common among younger patients and those with previous COVID-19. AEs were less common in individuals receiving advanced therapies with biologics or small-molecule inhibitors. DISCUSSION: Those with IBD and other immune-mediated inflammatory diseases can be reassured that the AE risk is likely not increased, and may be reduced, while on advanced therapies.

INTRODUCTION: This systematic review and meta-analysis aimed to determine the role of small intestinal bacterial overgrowth (SIBO) in patients with functional dyspepsia (FD). METHODS: Electronic databases were searched until July 2020 for studies reporting prevalence of SIBO in FD. The prevalence rates, odds ratio, and 95% confidence intervals (CIs) of SIBO in FD and controls were calculated. RESULTS: Seven studies with 263 patients with FD and 84 controls were identified. The odds for SIBO in patients with FD were significantly higher as compared to that in controls (odds ratio = 4.3, 95% CI, 1.1-17.5, 4 studies, 234 participants); however, there was moderate heterogeneity in this analysis. Including high-quality, case-control studies (all using glucose breath tests [GBTs]), the risk of SIBO in patients with FD as compared to controls was 2.8 higher (95% CI 0.8-10.0, 3 studies, 200 participants) with minimal heterogeneity in this analysis. Using the lactulose breath test, SIBO prevalence in FD was significantly higher (53.4%, 95% CI 33.9-71.9, 3 studies, 110 participants) as…

People living with hepatitis B virus (HBV) chronic infection are exposed to high rates of liver complications including end-stage liver disease and hepatocellular carcinoma. Extrahepatic manifestations of HBV infection have long been underestimated. Several of these extrahepatic syndromes have been well described, including systemic vasculitides, glomerulonephritis, and cutaneous manifestations. Other manifestations have been more recently described such as hematological malignancies and neurological diseases. These extrahepatic manifestations are associated with significant morbidity and mortality. Although not completely understood, underlying mechanisms include HBV-induced local and systemic inflammation. Suppression of HBV replication usually improves extrahepatic manifestations. This review will discuss how HBV induces inflammation and the extrahepatic manifestations of HBV infection to guide clinical management.

Abstract Background A claimed advantage of colonoscopy over sigmoidoscopy in colorectal cancer (CRC) screening is prevention of CRC not only in the distal colon and rectum but also in the proximal colon. We aimed to assess the association of screening colonoscopy use with overall and site-specific CRC incidence and associated mortality. Methods Information on use of screening colonoscopy as well as potential confounding factors was obtained at baseline in 2000-2002, updated at 2-, 5-, and 8-year follow-up from 9207 participants aged 50-75 years without history of CRC in a statewide cohort study in Saarland, Germany. Covariate-adjusted associations of screening colonoscopy with CRC incidence and mortality, which were obtained through record linkage with the Saarland Cancer Registry and mortality statistics up to 2016, were assessed by Cox proportional hazards models with time-varying exposure information. Findings During a median follow-up of 15·3 years, 227 participants were diagnosed with CRC and 81 died from CRC. Screening colonoscopy was associated with strongly reduced overall…

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard…

INTRODUCTION: A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. METHODS: Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. RESULTS: Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 μg/g in at least 1 fecal sample was seen in…

INTRODUCTION: Digital health technologies may be useful tools in the management of chronic diseases. We performed a systematic review of digital health interventions in the management of patients with inflammatory bowel diseases (IBD) and evaluated its impact on (i) disease activity monitoring, (ii) treatment adherence, (iii) quality of life (QoL) measures, and/or (iv) health care utilization. METHODS: Through a systematic review of multiple databases through August 31, 2020, we identified randomized controlled trials in patients with IBD comparing digital health technologies vs standard of care (SoC) for clinical management and monitoring and reporting impact on IBD disease activity, treatment adherence, QoL, and/or health care utilization or cost-effectiveness. We performed critical qualitative synthesis of the evidence supporting digital health interventions in patients with IBD and rated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Overall, we included 14 randomized controlled trials (median, 98 patients; range 34-909…

INTRODUCTION: The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown. METHODS: This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA: 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693). RESULTS: Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8;…

This document is a focused update to the 2017 colorectal cancer (CRC) screening recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer, which represents the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. This update is restricted to addressing the age to start and stop CRC screening in average-risk individuals and the recommended screening modalities. Although there is no literature demonstrating that CRC screening in individuals under age 50 improves health outcomes such as CRC incidence or CRC-related mortality, sufficient data support the U.S. Multi-Society Task Force to suggest average-risk CRC screening begin at age 45. This recommendation is based on the increasing disease burden among individuals under age 50, emerging data that the prevalence of advanced colorectal neoplasia in individuals ages 45 to 49 approaches rates in individuals 50 to 59, and modeling studies that demonstrate the benefits of screening outweigh the potential harms and costs. For individuals…

INTRODUCTION: The management of chronic liver diseases (CLDs) and cirrhosis is associated with substantial healthcare costs. We aimed to estimate trends in national healthcare spending for patients with CLDs or cirrhosis between 1996 and 2016 in the United States. METHODS: National-level healthcare expenditure data developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project and prevalence of CLDs and cirrhosis derived from the Global Burden of Diseases Study were used to estimate temporal trends in inflation-adjusted US healthcare spending, stratified by setting of care (ambulatory, inpatient, emergency department, and nursing care). Joinpoint regression was used to evaluate temporal trends, expressed as annual percent change (APC) with 95% confidence intervals (CIs). Drivers of change in spending for ambulatory and inpatient services were also evaluated. RESULTS: Total expenditures in 2016 were $32.5 billion (95% CI, $27.0-$40.4 billion). Over 65% of spending was for inpatient or emergency department care. From 1996 to 2016, there was a…

INTRODUCTION: Endoscopy-related injury (ERI) is common in gastroenterologists (GI). The study aim was to assess the prevalence of self-reported ERI, patterns of injury, and endoscopist knowledge of preventative strategies in a nationally representative sample. METHODS: A 38-item electronic survey was sent to 15,868 American College of Gastroenterology physician members. The survey was completed by 1,698 members and was included in analyses. Descriptive, univariate, and multivariate analyses were conducted to evaluate the likelihood of ERI based on workload parameters and gender. RESULTS: ERI was reported by 75% of respondents. ERI was most common in the thumb (63.3%), neck (59%), hand/finger (56.5%), lower back (52.6%), shoulder (47%), and wrist (45%). There was no significant difference in the prevalence of ERI between men and women GI. However, women GI were significantly more likely to report upper extremity ERI while men were more likely to report lower-back pain-related ERI. Significant gender differences were noted in the reported mechanisms attributed to ERI. Most respondents…

INTRODUCTION: The bleeding source of hematochezia is unknown without performing colonoscopy. We sought to identify whether colonoscopy is a risk-stratifying tool to identify etiology and predict outcomes and whether presenting symptoms can differentiate the etiologies in patients with hematochezia. METHODS: This multicenter retrospective cohort study conducted at 49 hospitals across Japan analyzed 10,342 patients admitted for outpatient-onset acute hematochezia. RESULTS: Patients were mostly elderly population, and 29.5% had hemodynamic instability. Computed tomography was performed in 69.1% and colonoscopy in 87.7%. Diagnostic yield of colonoscopy reached 94.9%, most frequently diverticular bleeding. Thirty-day rebleeding rates were significantly higher with diverticulosis and small bowel bleeding than with other etiologies. In-hospital mortality was significantly higher with angioectasia, malignancy, rectal ulcer, and upper gastrointestinal bleeding. Colonoscopic treatment rates were significantly higher with diverticulosis, radiation colitis, angioectasia, rectal ulcer, and…

INTRODUCTION: Psychological comorbidities are associated with irritable bowel syndrome (IBS), but little is known about their cumulative effect on its prognosis. We examined this issue in a longitudinal 12-month follow-up study. METHODS: We collected complete demographic, symptom, and psychological comorbidity data (anxiety, depression, somatic symptom disorder, perceived stress, and gastrointestinal symptom-specific anxiety) at baseline from 807 adults who met Rome IV criteria for IBS. At 12 months, we collected data regarding IBS symptom severity and impact, consultation behavior, and treatments commenced from 452 individuals successfully followed up. We examined the cumulative effects of psychological comorbidities at baseline on subsequent IBS disease behavior. RESULTS: At baseline, among the 807 participants, 177 (21.9%) had 1, 139 (17.2%) 2, 103 (12.8%) 3, 89 (11.0%) 4, and 54 (6.7%) 5 psychological comorbidities. IBS symptom severity at baseline increased significantly with the number of psychological comorbidities (72.2% of those with 5 psychological comorbidities reported…

INTRODUCTION: Cirrhosis is associated with cardiac dysfunction and distinct electrocardiogram (ECG) abnormalities. This study aimed to develop a proof-of-concept deep learning-based artificial intelligence (AI) model that could detect cirrhosis-related signals on ECG and generate an AI-Cirrhosis-ECG (ACE) score that would correlate with disease severity. METHODS: A review of Mayo Clinic's electronic health records identified 5,212 patients with advanced cirrhosis ≥18 years who underwent liver transplantation at the 3 Mayo Clinic transplant centers between 1988 and 2019. The patients were matched by age and sex in a 1:4 ratio to controls without liver disease and then divided into training, validation, and test sets using a 70%-10%-20% split. The primary outcome was the performance of the model in distinguishing patients with cirrhosis from controls using their ECGs. In addition, the association between the ACE score and the severity of patients' liver disease was assessed. RESULTS: The model's area under the curve in the test set was 0.908 with 84.9% sensitivity and 83.2%…

INTRODUCTION: Current guidelines recommend anticoagulation as the mainstay of portal vein thrombosis (PVT) treatment in cirrhosis. However, because of the heterogeneity of PVT, anticoagulation alone does not always achieve satisfactory results. This study aimed to prospectively evaluate an individualized management algorithm using a wait-and-see strategy (i.e., no treatment), anticoagulation, and transjugular intrahepatic portosystemic shunt (TIPS) to treat PVT in cirrhosis. METHODS: Between February 2014 and June 2018, 396 consecutive patients with cirrhosis with nonmalignant PVT were prospectively included in a tertiary care center, of which 48 patients (12.1%) were untreated, 63 patients (15.9%) underwent anticoagulation, 88 patients (22.2%) underwent TIPS, and 197 patients (49.8%) received TIPS plus post-TIPS anticoagulation. The decision of treatment option mainly depends on the stage of liver disease (symptomatic portal hypertension or not) and degree and extension of thrombus. RESULTS: During a median 31.7 months of follow-up period, 312 patients (81.3%) achieved partial (n =…

INTRODUCTION: We aimed to improve our understanding of the epidemiology of squamous cell carcinoma and adenocarcinoma of the esophagus. METHODS: We estimated average annual percent change and analyzed age-period-cohort trends on population-based cancer data. RESULTS: We found decreases in squamous cell carcinoma incidence in half of male populations (largest decrease in US black males [average annual percent change -7.6]) and increases in adenocarcinoma incidence in nearly a third of populations. Trends may be associated with a mix of birth cohort and period effects. DISCUSSION: More complete data and evidence are needed to conclude the reasons for the observed trends (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/AJG/B823).

INTRODUCTION: Psyllium and prunes are proven treatments for chronic constipation (CC). Asian studies suggest that kiwifruit may also benefit CC symptoms. We report a partially randomized, comparative effectiveness trial evaluating kiwifruit, psyllium, and prunes in US patients with CC. METHODS: Adults with CC at a US medical center were randomized to 3 natural treatments. Eligible patients had ≤3 complete spontaneous bowel movements (CSBMs) per week and were partially randomized to green kiwifruit (2/d), prunes (100 g/d), or psyllium (12 g/d) for 4 weeks. The primary endpoint was the proportion of patients in each group reporting an increase of ≥1 CSBM per week compared with baseline for at least 2 of 4 treatment weeks. Key secondary outcomes included stool frequency, stool consistency, and straining assessed daily. Treatment satisfaction and adverse events (AEs) were also measured. Standard statistical methods were used, and a P < 0.05 was considered significant. RESULTS: Seventy-nine patients with CC (mean age = 42.7 years, 87% female, and 77% white) were partially randomized.…

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI…

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS). METHODS: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red…

INTRODUCTION: Immunotherapy has dramatically improved the survival of patients with advanced or metastatic malignancies. Recent studies suggest that immunotherapy may increase the risk of hepatitis, whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy. METHODS: This was a territory-wide observational cohort study in Hong Kong. We identified patients through electronic medical records based on the prescriptions of immune checkpoint inhibitors from July 1, 2014, to December 31, 2019. Patients who were HBsAg positive or HBsAg negative with results for antibody to hepatitis B surface or core antigen (anti-HBs or anti-HBc) were included. RESULTS: A total of 990 patients (397 HBsAg-positive, 593 HBsAg-negative with 482 anti-HBc and/or anti-HBs positive, and 111 both anti-HBc and anti-HBs negative) were identified. All of HBsAg-positive and 15.9%…

INTRODUCTION: Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS). METHODS: Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week). RESULTS: Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant…

Chronic abdominal pain is a common gastrointestinal (GI) symptom that characterizes many functional GI disorders/disorders of gut-brain interaction, including irritable bowel syndrome, functional dyspepsia, and centrally mediated abdominal pain syndrome. The symptoms of abdominal pain in these highly prevalent disorders are often treated with antispasmodic agents. Antispasmodic treatment includes a broad range of therapeutic classes with different mechanisms of action, including anticholinergic/antimuscarinic agents (inhibition of GI smooth muscle contraction), calcium channel inhibitors (inhibition of calcium transport into GI smooth muscle), and direct smooth muscle relaxants (inhibition of sodium and calcium transport). The aim of this review article was to examine the efficacy and safety of antispasmodics available in North America (e.g., alverine, dicyclomine, hyoscine, hyoscyamine, mebeverine, otilonium, pinaverium, and trimebutine) for the treatment of chronic abdominal pain in patients with common disorders of gut-brain interaction. For the agents examined, comparisons of…

INTRODUCTION: To estimate the annual incidence of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis, to determine the risk factors for the development of HCC, and to evaluate the chemoprotective effect of statin use stratified by fibrosis stage. METHODS: We conducted a retrospective study at 2 US tertiary academic centers, including patients with NASH-related advanced liver fibrosis (bridging fibrosis [F3] and cirrhosis [F4]) followed between July 2002 and June 2016. Patients were followed from the date of diagnosis to the time of last abdominal imaging, liver transplantation, or HCC diagnosis. Multivariable Cox regression analysis was performed to evaluate the risk factors associated with HCC development, stratified by fibrosis stage. RESULTS: A total of 1,072 patients were included: 122 patients with F3 fibrosis and 950 patients with cirrhosis. No HCC was observed during 602 person-year follow-up among F3 patients. Among patients with cirrhosis, HCC developed in 82 patients with the annual incidence rate of 1.90 per…

INTRODUCTION: Differentiating mucinous neoplastic pancreatic cysts (MNPC) from cysts without malignant potential can be challenging. Guidelines recommend using fluid carcinoembryonic antigen (CEA) to differentiate MNPC; however, its sensitivity and specificity vary widely. Intracystic glucose concentration has shown promise in differentiating MNPC, but data are limited to frozen specimens and cohorts of patients without histologic diagnoses. This study aimed to compare glucose and CEA concentrations in differentiating MNPC using fresh fluid obtained from cysts with confirmatory histologic diagnoses. METHODS: This multicenter cohort study consisted of patients undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic cysts during January 2013-May 2020. Patients were included if the cyst exhibited a histologic diagnosis and if both CEA and glucose were analyzed from fresh fluid. Receiver operating curve (ROC) characteristics were analyzed, and various diagnostic parameters were compared. RESULTS: Ninety-three patients, of whom 59 presented with MNPC, met…

INTRODUCTION: Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables. METHODS: The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort. RESULTS: Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures…

INTRODUCTION: Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD. METHODS: Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively. RESULTS: Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD…

INTRODUCTION: Patients with inflammatory bowel disease (IBD) on immune-modifying therapies may have a lower vaccine response to certain vaccines. The aim of our study was to evaluate humoral immunogenicity of mRNA coronavirus disease 2019 (COVID-19) vaccines among patients with IBD and healthy controls (HCs). METHODS: We performed a prospective study to evaluate humoral immunogenicity among patients with IBD and HCs after completion of mRNA COVID-19 vaccines. RESULTS: One hundred twenty-two patients with IBD and 60 HCs were enrolled. All HCs and 97% of patients with IBD developed antibodies. Antibody concentrations were lower in patients with IBD compared with those in HCs (median 31 vs 118 μg/mL; P < 0.001). Those who received the mRNA-1273 (Moderna) COVID-19 (median 38; interquartile range [IQR] 24-75 vs μg/mL) had higher antibody concentrations compared with those who received the Pfizer-BNT vaccine series (median 22; IQR 11-42 μg/mL; P < 0.001). Patients on immune-modifying therapy (median 26; IQR 13-50 μg/mL) had lower antibody concentrations compared with those who were on no…

INTRODUCTION: Adenoma detection rate (ADR) is highly variable across practices, and national or population-based estimates are not available. Our aim was to study the ADR, variability of rates over time, and factors associated with detection rates of ADR in a national sample of patients undergoing colonoscopy. METHODS: We used colonoscopies submitted to the GI Quality Improvement Consortium, Ltd. registry from 2014 to 2018 on adults aged 50-89 years. We used hierarchical logistic models to study factors associated with ADR. RESULTS: A total of 2,646,833 colonoscopies were performed by 1,169 endoscopists during the study period. The average ADR for screening colonoscopies per endoscopist was 36.80% (SD 10.21), 44.08 (SD 10.98) in men and 31.20 (SD 9.65) in women. Adjusted to the US population, the ADR was 39.08%. There was a significant increase in ADR from screening colonoscopies over the study period from 33.93% in 2014 to 38.12% in 2018. DISCUSSION: The average ADR from a large national US sample standardized to the US population is 39.05% and has increased over time.

INTRODUCTION: Patients with cirrhosis and men have been under-represented in most studies examining the clinical benefit of response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC). The aim of this study was to study the association of UDCA response and liver-related death or transplantation, hepatic decompensation, and hepatocellular carcinoma (HCC) in patients with PBC cirrhosis. METHODS: We conducted a retrospective cohort study of veterans, predominantly men, with PBC and compensated cirrhosis to assess the association of UDCA response with the development of all-cause and liver-related mortality or transplantation, hepatic decompensation, and HCC using competing risk time-updating Cox proportional hazards models. RESULTS: We identified 501 subjects with PBC and compensated cirrhosis, including 287 UDCA responders (1,692.8 patient-years [PY] of follow-up) and 214 partial responders (838.9 PY of follow-up). The unadjusted rates of hepatic decompensation (3.8 vs 7.9 per 100 PY, P < 0.0001) and liver-related death or transplantation (3.7 vs 6.2 per 100 PY, P <…

INTRODUCTION: Evidence regarding the association between alcohol use and gastric cancer (GC) has been inconsistent. METHODS: Adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010 were included. Multivariable regression was used to assess the association between GC and heavy alcohol use (≥5 alcoholic drinks daily). RESULTS: Of 470,168 individuals surveyed, 342 had a history of GC. Heavy alcohol use was associated with GC (odds ratio 3.13, 95% confidence interval 1.15-8.64) on multivariable analysis. DISCUSSION: This is the largest study to our knowledge to demonstrate an association between heavy alcohol use and GC in the United States.

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy…

INTRODUCTION: The current therapy of neoplastic Barrett's esophagus (BE) consists of endoscopic resection plus ablation, with radiofrequency ablation as the best studied technique. This prospective trial assesses a potential alternative, namely hybrid argon plasma ablation. METHODS: Consecutive patients with neoplastic BE undergoing ablation after curative endoscopic resection (89.6%) or primarily were included into this prospective trial in 9 European centers. Up to 5 ablation sessions were allowed for complete eradication of BE (initial complete eradication of intestinal metaplasia [CE-IM]), by definition including BE-associated neoplasia, documented by 1 negative endoscopy with biopsies. The main outcome was the rate of initial CE-IM in intention-to-treat (ITT) and per-protocol (PP) samples at 2 years. The secondary end points were the rate of recurrence-free cases (sustained CE-IM) documented by negative follow-up endoscopies with biopsies and immediate/delayed adverse events. RESULTS: One hundred fifty-four patients (133 men and 21 women, mean age 64 years) received a mean of…

INTRODUCTION: Venous thromboembolism (VTE) is known to be increased in inflammatory bowel disease (IBD). We aimed to determine whether rates of VTE in IBD have reduced over the past 30 years. METHODS: We used the population-based University of Manitoba IBD Epidemiology Database (1984-2018) to determine the incidence of VTE in IBD and the incidence rate ratio vs matched controls. In persons with IBD with and without VTE, we assessed for variables that were associated with an increased risk of VTE on multivariate logistic regression. RESULTS: The incidence of VTE in the IBD cohort was 7.6% which was significantly greater than in controls (3.3%, P < 0.0001). The overall age-standardized incidence rate of VTE was 433 per 100,000 in IBD and 184 per 100,000 in controls. The incidence of VTE was higher in Crohn's disease (8.4%) than in ulcerative colitis (6.9%, P = 0.0028). The incidence rate ratio in IBD vs controls was 2.36 (95% confidence interval 2.16-2.58). The increased risk was similar in males and females and in Crohn's disease compared with ulcerative colitis. The incidence rate…

INTRODUCTION: The aim of this study was to investigate the effect of spontaneous sleep positions on the occurrence of nocturnal gastroesophageal reflux. METHODS: In patients referred for ambulatory pH-impedance reflux monitoring, the concurrent sleep position was measured using a sleep position measurement device (measuring left, right, supine, and prone positions). RESULTS: Fifty-seven patients were included. We observed a significantly shorter acid exposure time in the left (median 0.0%, P25-P75, 0.0%-3.0%), compared with the right lateral position (median 1.2%, 0.0%-7.5%, P = 0.022) and the supine position (median 0.6%, 0.00%-8.3%, P = 0.022). The esophageal acid clearance time was significantly shorter in the left lateral decubitus position (median 35 seconds, 16-115 seconds), compared with the supine (median 76 seconds, 22-257 seconds, P = 0.030) and right lateral positions (median 90 seconds, 26-250 seconds, P = 0.002). DISCUSSION: The left lateral decubitus position is associated with significantly shorter nocturnal esophageal acid exposure time and faster esophageal acid…

INTRODUCTION: Cold snare polypectomy (CSP) is safe and effective for the removal of small adenomas (≤10 mm); however, reported incomplete resection rates (IRRs) vary. The optimal CSP technique, where a wide margin of normal tissue is resected around the target lesion, and snare design have both been hypothesized to reduce the IRR after CSP. We sought to investigate the efficacy of a thin-wire versus thick-wire diameter snare on IRR, using the standardized CSP technique. METHODS: This was an international multicenter parallel design randomized trial with 17 endoscopists of varying experience (NCT02581254). Patients were randomized in a 1:1 ratio to the use of a thin-wire (0.30 mm) or thick-wire (0.47 mm) snare for CSP of small (≤10 mm) colorectal polyps. The primary end point was the IRR as determined by the histologic assessment of the defect margin after polypectomy. RESULTS: Over 52 months to January 2020, 1,393 patients were eligible. A total of 660 patients with polyps (57.4% male) were randomized to a thin-wire (n = 339) or thick-wire (n = 321) snare. The overall IRR of the…