The 100 most-cited articles in The American Journal of Gastroenterology, 2019

Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC 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 (GRADE) process. In instances where the evidence was not appropriate for GRADE, 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 only, approach to clinical scenarios.

OBJECTIVES: To systematically summarize the risk relationship between different levels of alcohol consumption and incidence of liver cirrhosis. METHODS: MEDLINE and Embase were searched up to March 6, 2019, to identify case-control and cohort studies with sex-specific results and more than 2 categories of drinking in relation to the incidence of liver cirrhosis. Study characteristics were extracted and random-effects meta-analyses and meta-regressions were conducted. RESULTS: A total of 7 cohort studies and 2 case-control studies met the inclusion criteria, providing data from 2,629,272 participants with 5,505 cases of liver cirrhosis. There was no increased risk for occasional drinkers. Consumption of one drink per day in comparison to long-term abstainers showed an increased risk for liver cirrhosis in women, but not in men. The risk for women was consistently higher compared to men. Drinking ≥5 drinks per day was associated with a substantially increased risk in both women (relative risk [RR] = 12.44, 95% confidence interval [CI]: 6.65-23.27 for 5-6 drinks, and RR = 24.58, 95%…

Hereditary hemochromatosis (HH) is one of the most common genetic disorders among persons of northern European descent. There have been recent advances in the diagnosis, management, and treatment of HH. The availability of molecular diagnostic testing for HH has made possible confirmation of the diagnosis for most patients. Several genotype-phenotype correlation studies have clarified the differences in clinical features between patients with the C282Y homozygous genotypes and other HFE mutation patterns. The increasing use of noninvasive tests such as MRI T2* has made quantification of hepatic iron deposition easier and eliminated the need for liver biopsy in most patients. Serum ferritin of <1,000 ng/mL at diagnosis remains an important diagnostic test to identify patients with a low risk of advanced hepatic fibrosis and should be used routinely as part of the initial diagnostic evaluation. Genetic testing for other types of HH is available but is expensive and generally not useful in most clinical settings. Serum ferritin may be elevated among patients with nonalcoholic fatty…

OBJECTIVES: In 2015, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program proposed shifting the therapeutic focus on ulcerative colitis (UC) toward altering the natural history of the disease course by regularly monitoring objective measurements of disease activity and tailoring treatment accordingly. The therapeutic paradigm shift was well received in the research community and is often cited. However, new evidence on optimal UC treatment targets continues to accumulate since the time of the STRIDE guidelines. This systematic review summarizes the evidence accrued since the STRIDE UC recommendations, discusses the barriers for adoption of treat-to-target approaches in clinical practice in UC, and suggests directions for future research. METHODS: We systematically reviewed MEDLINE for studies from the time of the STRIDE systematic review up to March 31, 2018, that assessed the potential treatment targets identified by the STRIDE recommendations. RESULTS: Each potential treatment target literature search returned > 200 articles, which were then reviewed by…

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT. METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed. RESULTS: Ten patients underwent FMT. Nine patients had ulcerative…

OBJECTIVES: Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is scarce. Prucalopride, a selective 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. In a double-blind, randomized, placebo-controlled crossover study, we evaluated the efficacy of prucalopride to improve the gastric emptying rate and symptoms in patients with gastroparesis. METHODS: Thirty-four patients with gastroparesis (28 idiopathic, 7 men, mean age 42 ± 13 years) were evaluated in a double-blind crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks of washout. The primary end point was the change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life, and daily diaries, and the gastric emptying rate was assessed by the C-octanoic…

OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS. METHODS: We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement. RESULTS: Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met…

BACKGROUND: The incidence of young-onset colorectal cancer (CRC) is reported to be increasing in the Western world. There are no population-based studies assessing the trend across Asia. METHODS: We performed a multinational cohort study involving four Asian countries/regions, namely Taiwan, Korea, Japan, and Hong Kong. The magnitude and direction of trend in the incidence of young-onset CRC (age < 50) were quantified using Joinpoint Regression Program to estimate average annual percentage change (AAPC). RESULTS: In Taiwan (1995-2014), incidence of young-onset CRC significantly increased in both men (colon cancer: 4.9-9.7 per 100,000; rectal cancer: 4.0-8.3 per 100,000) and women (colon cancer: 5.1-9.7 per 100,000; rectal cancer: 3.8-6.4 per 100,000). In Korea (1999-2014), incidence of young-onset CRC significantly increased in both men (colon cancer: 5.0-10.4 per 100,000; rectal cancer: 4.9-14.0 per 100,000) and women (colon cancer: 4.1-9.6 per 100,000; rectal cancer: 4.1-9.1 per 100,000). The most pronounced change was observed with male rectal cancer, increasing by 3.9% per year…

Financial Support and Acknowledgements Support for this project was provided through a research training grant as part of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) (U54 AI117804). CEGIR is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS. CEGIR is also supported by patient advocacy groups including APFED CURED and EFC. This project also received support from NIH T32 DK007634 (CCR). Author Disclosers Patricia Fulkerson: Grant funding from the NIH; Consultant for Genentech, Inc; Research support from Knopp Biosciences, LLC. Gary Falk: Research support from Shire, Celgene, Adare, Regeneron. Consulting for Shire Jonathan M. Spergel: Consultant for Regeneron, DBV Technology, Kaleo; Grant funding from DBV Technology, Aimmune Therapeutics, Food Allergy Research Education; Royalties from UpToDate Nirmala Gonsalves: Royalties from UpToDate; Advisory board for Allakos Sandeep K Gupta: Consultant for Alkalos,…

OBJECTIVES: Accumulating evidence indicates that the gut microbiota communicates with the central nervous system, possibly through neural, endocrine, and immune pathways, and influences brain function. B. longum 1714™ has previously been shown to attenuate cortisol output and stress responses in healthy subjects exposed to an acute stressor. However, the ability of B. longum 1714™ to modulate brain function in humans is unclear. METHODS: In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714™ on neural responses to social stress, induced by the "Cyberball game," a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714™ or placebo for 4 weeks at a dose of 1 × 10 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey. RESULTS: B. longum 1714™ altered resting-state neural oscillations, with an increase in theta band power in the frontal and cingulate cortex (P < 0.05) and a decrease in beta-3 band in the hippocampus, fusiform, and…

Chronic pancreatitis is characterized by progressive, irreversible morphologic and functional changes that are most commonly attributed to environmental insults, particularly when there is a genetic or anatomic predisposition. Heavy alcohol use and cigarette smoking are the most common environmental risk factors, but both may be absent. Antecedent episodes of acute pancreatitis occur in about half of patients. Abdominal pain is the most common symptom and requires a tailored approach depending on the anatomic changes in the pancreas. Other clinical manifestations include diabetes mellitus, exocrine pancreatic insufficiency, metabolic bone disease, pancreatic cancer, and anatomic complications. Current disease management is centered on risk factor reduction and screening for and treating disease complications. There are no current therapies to delay or retard disease progression, but there are ongoing efforts to more fully understand the natural history of chronic pancreatitis and underlying mechanisms of disease. These studies are expected to provide insights that will transform our…

OBJECTIVES: Alcoholic liver disease (ALD) prevalence, particularly the subset with advanced liver disease, is not well defined. Herein, we aim to provide a comprehensive assessment of ALD epidemiology across the spectrum of disease severity and across different settings using 3 unique US databases. METHODS: We performed a retrospective, observational study of US adults with ALD using 2001-2016 National Health and Nutrition Examination Survey (NHANES), 2007-2014 Nationwide Inpatient Sample (NIS), and 2007-2017 United Network for Organ Sharing (UNOS) registry. ALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67 defined stage ≥3 fibrosis. Alcoholic cirrhosis (AC) in the NIS was identified using International Classification of Diseases, Ninth Revision codes. ALD in the UNOS was identified using UNOS coding. RESULTS: From 2001-2002 to 2015-2016, the overall weighted ALD prevalence was stable from 8.8% to 8.1% (P = 0.102), whereas the proportion of ALD with stage ≥3 fibrosis increased from 2.2% (95% CI: 0.4-4.0)…

OBJECTIVES: Reliable in situ diagnosis of diminutive (≤5 mm) colorectal polyps could allow for "resect and discard" and "diagnose and leave" strategies, resulting in $1 billion cost savings per year in the United States alone. Current methodologies have failed to consistently meet the Preservation and Incorporation of Valuable endoscopic Innovations (PIVIs) initiative thresholds. Convolutional neural networks (CNNs) have the potential to predict polyp pathology and achieve PIVI thresholds in real time. METHODS: We developed a CNN-based optical pathology (OP) model using Tensorflow and pretrained on ImageNet, capable of operating at 77 frames per second. A total of 6,223 images of unique colorectal polyps of known pathology, location, size, and light source (white light or narrow band imaging [NBI]) underwent 5-fold cross-training (80%) and validation (20%). Separate fresh validation was performed on 634 polyp images. Surveillance intervals were calculated, comparing OP with true pathology. RESULTS: In the original validation set, the negative predictive value for adenomas was 97%…

OBJECTIVES: This study assessed the effectiveness, adverse events, patient adherence, and costs of modified dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori infection in Chinese patients. We also sought to determine whether modified dual therapy could be used as an alternative first-line treatment for H. pylori infection. METHODS: A total of 232 H. pylori-infected, treatment-naive patients were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day modified dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the 2 groups. RESULTS: The modified dual therapy group achieved eradication rates of 87.9%, 91.1%, and 91.1% as determined by the intention-to-treat, per-protocol, and modified intention-to-treat analyses, respectively. The eradication rates were similar compared with the bismuth-containing quadruple therapy group: 89.7%, 91.2%, and 90.4%.…

Rumination syndrome (RS) is characterized by the repeated regurgitation of material during or soon after eating with the subsequent rechewing, reswallowing, or spitting out of the regurgitated material. Rumination syndrome is classified as both a "Functional Gastroduodenal Disorder" (by the Rome Foundation's Functional Gastrointestinal Disorders: Disorders of Gut-Brain Interaction, 4th edition) and a "Feeding and Eating Disorder" (by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition). Rumination syndrome is a disorder that is often inaccurately diagnosed or missed, resulting in patients experiencing protracted symptoms and not receiving treatment for long periods. There is a lack of clear consensus for RS diagnosis, mechanisms that maintain RS, and treatment. Guided by existing research and our clinical expertise, we synthesize available evidence and provide recommendations for clinical use. We present a case example and critically summarize the literature to date to (i) increase clinicians' understanding of heterogeneous clinical presentations, (ii) suggest…

OBJECTIVE: Fecal immunochemical tests (FITs) detect the majority of colorectal cancers (CRCs), but evidence for variation in sensitivity according to the CRC stage is sparse and has not yet been systematically synthesized. Thus, our objective was to systematically review and summarize evidence on the stage-specific sensitivity of FITs. METHODS: We screened PubMed, Web of Science, Embase, and the Cochrane Library from inception to June 14, 2019, for English-language articles reporting on the stage-specific sensitivity of FIT for CRC detection using colonoscopy as a reference standard. Studies reporting stage-specific sensitivities and the specificity of FIT for CRC detection were included. Summary estimates of sensitivity according to the CRC stage and study setting (screening cohorts, symptomatic/diagnostic cohorts, and case-control studies) were derived from bivariate meta-analysis. RESULTS: Forty-four studies (92,447 participants including 3,034 CRC cases) were included. Pooled stage-specific sensitivities were overall very similar but suffered from high levels of imprecision…

OBJECTIVES: Eosinophilic esophagitis (EoE), a chronic food allergic disease, lacks sensitive and specific peripheral biomarkers. We hypothesized that levels of EoE-related biomarkers captured using a 1-hour minimally invasive Esophageal String Test (EST) would correlate with mucosal eosinophil counts and tissue concentrations of these same biomarkers. We aimed to determine whether a 1-hour EST accurately distinguishes active from inactive EoE or a normal esophagus. METHODS: In a prospective, multisite study, children and adults (ages 7-55 years) undergoing a clinically indicated esophagogastroduodenoscopy performed an EST with an esophageal dwell time of 1 hour. Subjects were divided into 3 groups: active EoE, inactive EoE, and normal esophageal mucosa. Eosinophil-associated protein levels were compared between EST effluents and esophageal biopsy extracts. Statistical modeling was performed to select biomarkers that best correlated with and predicted eosinophilic inflammation. RESULTS: One hundred thirty-four subjects (74 children, 60 adults) with active EoE (n = 62), inactive EoE…

INTRODUCTION: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: This retrospective cohort study analyzed an international consortium that encompassed 19 centers from 6 countries or regions composed of previously untreated CHB patients then treated with either ETV or TDF monotherapy. Those who developed HCC before antiviral treatment or within 1 year of therapy were excluded. The association between antiviral regimen and HCC risk was evaluated using competing-risk survival regression. We also applied propensity score matching (PSM) to 1:1 balance the 2 treatment cohorts. A total of 5,537 patients were eligible (n = 4,837 received ETV and n = 700 received TDF) and observed for HCC occurrence until December 23, 2018. Before PSM, the TDF cohort was significantly younger and had generally less advanced diseases. RESULTS: In the unadjusted analysis, TDF was associated with a lower risk of HCC (subdistribution hazard ratio [SHR], 0.45;…

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27%…

INTRODUCTION: Some evidence suggests an interference of obesity and alanine aminotransferase (ALT) levels on the diagnostic accuracy for advanced fibrosis of noninvasive tools such as liver stiffness measurement (LSM) by FibroScan, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score (NFS). We assessed whether the diagnostic accuracy of LSM, Fibrosis-4 (FIB-4), and NFS and strategies based on the combination of these tools is affected by obesity and/or ALT levels. METHODS: We analyzed data from 968 patients with a histological diagnosis of nonalcoholic fatty liver disease. FIB-4, NFS, and LSM by FibroScan were measured. RESULTS: LSM was better than both FIB-4 and NFS for staging F3-F4 fibrosis area under the receiver operating characteristic curve test (AUC) 0.863, 0.777, and 0.765, respectively; P < 0.001 for both), showing higher accuracy and higher negative predictive value (NPV), but lower positive predictive value (PPV). LSM worked less well in high ALT (>100 IU) (AUC 0.811 vs 0.877, P = 0.04; PPV 57.5% vs 62.4%; NPV 90.7% vs 94%) or obese patients (AUC 0.786…

INTRODUCTION: We conducted this study to characterize the incidence, clinical features, treatment, and outcomes of immune checkpoint inhibitor (ICI) hepatotoxicity. METHODS: Patients who received ICIs (with either single-agent or combination regimens) from January 1, 2010, to March 31, 2018, were identified. Hepatotoxicity was defined as alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN), in the absence of an alternate cause, and categorized as grade 3 (ALT 5-20× ULN) or grade 4 (ALT >20× ULN), according to Common Terminology Criteria for Adverse Events 4.03. RESULTS: Among 5,762 patients, 100 (2%) developed hepatotoxicity, occurring in a higher proportion of recipients of combination therapy (9.2%) compared with monotherapy (up to 1.7%, P < 0.001). ICIs were discontinued permanently in 69 and temporarily in 31 patients. Sixty-seven patients received steroids, 10 of whom (14%) had recurrent hepatotoxicity after the steroid taper. Thirty-one patients resumed ICIs after ALT improvement, 8 of whom (26%) developed recurrent hepatotoxicity. Characteristics of liver…

OBJECTIVES: Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS: We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS: The prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet…

OBJECTIVES: The management of small and incidental branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) still is of concern. The aim is assessing the safety of a surveillance protocol through the evaluation of their progression to malignancy. METHODS: All presumed BD-IPMNs observed from 2000 to 2016 were included. Only patients presenting without worrisome features (WFs) and high-risk stigmata (HRS) at diagnosis were included. Development of WF, HRS, pancreatic cancer (PC), and survival were analyzed. BD-IPMNs were defined as trivial in the continuing absence of WF/HRS after 5 years of surveillance. The age-specific standardized incidence ratio of PC in the general population was used for comparison. RESULTS: A total of 1,036 BD-IPMNs without WF/HRS at diagnosis were included, 4.2% developed WF or HRS, and 1.1% developed PC after a median of 62 months. The median cyst growth rate was 0 mm/yr. A growth rate ≥2.5 mm/yr and the development of WF resulted independent predictors of PC. The standardized incidence ratio of PC for trivial BD-IPMN (n = 378) was 22.45 (95%…

INTRODUCTION: To compare the utility of the distensibility index (DI) on functional lumen imaging probe (FLIP) topography to other esophagogastric junction (EGJ) metrics in assessing treatment response in achalasia in the context of esophageal anatomy. METHODS: We prospectively evaluated 79 patients (at ages 17-81 years; 47% female patients) with achalasia during follow-up after pneumatic dilation, Heller myotomy, or per-oral endoscopic myotomy with timed barium esophagram, high-resolution impedance manometry, and FLIP. Anatomic deformities were identified based on consensus expert opinion. Patients were classified based on anatomy and EGJ opening to determine the association with radiographic outcome and Eckardt score (ES). RESULTS: Twenty-seven patients (34.1%) had an anatomic deformity-10 pseudodiverticula at myotomy, 7 epiphrenic diverticula, 5 sigmoid, and 5 sinktrap. A 5-minute column area of >5 cm was best associated with an ES of >3, with a sensitivity of 84% (P = 0.0013). Area under the curve for EGJ metrics in association with retention was as follows: DI, 0.90; maximal…

INTRODUCTION: The objective was to assess the efficacy and safety of GED-0301, an antisense oligodeoxynucleotide to Smad7, in active Crohn's disease (CD). METHODS: This phase 3, blinded study randomized patients (1:1:1:1) to placebo or 1 of 3 once-daily oral GED-0301 regimens: 160 mg for 12 weeks followed by 40 mg continuously or alternating placebo with 40 or 160 mg every 4 weeks through week 52. RESULTS: In all, 701 patients were randomized and received study medication before premature study termination; 78.6% (551/701) completed week 12, and 5.8% (41/701) completed week 52. The primary endpoint, clinical remission achievement (CD Activity Index score <150) at week 12, was attained in 22.8% of patients on GED-0301 vs 25% on placebo (P = 0.6210). At study termination, proportions of patients achieving clinical remission at week 52 were similar among individual GED-0301 groups and placebo. More placebo vs GED-0301 patients achieved endoscopic response (>50% decrease from baseline Simple Score for CD) at week 12 (18.1% vs 10.1%). Additional endoscopic endpoints were similar between…

Celiac disease is a common inflammatory disease triggered by dietary gluten in genetically susceptible individuals. The strongest and best-characterized genetic susceptibilities in celiac disease are class II human leukocyte antigen (HLA) genes known as HLA-DQ2 and DQ8. HLA genetic testing is available through a number of commercial and academic laboratories and is used in the evaluation of celiac disease and to identify at-risk family members. Importantly, HLA genetic testing has a high negative predictive value for celiac disease, but a low positive predictive value. Therefore, for a practicing clinician, it is important to understand when to order HLA genetic testing, what test to order, and how to interpret the result. This review provides a practical primer on HLA genetics in celiac disease.

In recent years, the therapeutic goals in ulcerative colitis (UC) have become increasingly stringent. Histological features seem to be a reliable predictor of disease outcomes after therapy, and histological remission (HR) is the new frontier in the treatment of UC. Here, we first provide a historical perspective before reviewing indexes in the era of biologics; histology as a treatment goal in UC trials; the poor correlation between symptoms, endoscopy, and histology; and the impact of histology on disease outcomes. HR seems to be a promising end point for the treatment of UC because it is typically associated with better outcomes. Two new validated indexes are available to assess histology more accurately in trials, and they may also be applicable to clinical practice. Additional interventional trials are now necessary to establish definitions of HR and its potential for disease modification.

INTRODUCTION: Ammonia appears to play a major role in the pathophysiology of hepatic encephalopathy (HE), but its role in guiding management is unclear. We aimed to understand the impact of ammonia levels on inpatient HE management, hypothesizing that patients with elevated ammonia levels would receive more aggressive lactulose therapy than patients with normal ammonia or no ammonia level drawn. METHODS: We examined patients with cirrhosis older than 18 years admitted for management of HE from 2005 to 2015. We additionally used propensity matching to control for confounding by the severity of underlying disease. Patients with an ammonia level taken at time of HE diagnosis were further separated into those with normal or elevated ammonia levels. The primary endpoint was the total lactulose (mL) amount (or dose) given in the first 48 hours of HE management. RESULTS: One thousand two hundred two admissions with HE were identified. Ammonia levels were drawn in 551 (46%) patients; 328 patients (60%) had an abnormal ammonia level (>72 μmol/L). There were no significant differences in the…

INTRODUCTION: We conducted a cohort study on the impact of obesity on disease activity and Patient-Reported Outcomes Measurement Information System (PROMIS) measures in the inflammatory bowel disease (IBD) Partners cohort. METHODS: We performed a cross-sectional and longitudinal study within IBD Partners, an internet-based cohort of >15,000 patients living with Crohn's disease (CD) and ulcerative colitis (UC). We included adult patients with IBD, with recorded body mass index (BMI), with at least 6 months of follow-up, excluding patients with BMI < 18.5 kg/m. We evaluated the independent effect of World Health Organization classes of obesity on risk of clinical relapse or persistent disease activity (using validated disease activity indexes) and PROMIS measures, using multivariate logistic regression and linear regression, respectively. RESULTS: We included 7,296 patients with IBD (4,748 patients with CD, 19.5% obese; 2,548 patients with UC with intact colon, 20.3% obese). Obesity was independently, and in a dose-dependent fashion, associated with an increased risk of persistent…

OBJECTIVES: To investigate the risk of mortality and hospitalization in individuals with post-pancreatitis diabetes mellitus (PPDM) compared with those with type 2 diabetes mellitus (T2DM). METHODS: Using nationwide hospital discharge data on pancreatitis and diabetes in New Zealand (n = 231,943), a total of 959 individuals with PPDM were identified. For each individual with PPDM, 10 age- and sex-matched individuals with T2DM were randomly selected. Multivariable Cox regression analysis was conducted, and the risk was expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3,867 deaths occurred among 10,549 study individuals. Individuals with PPDM had all-cause mortality rate at 80.5 (95% CI, 70.3-90.6) per 1,000 person-years, which was higher compared with T2DM individuals (adjusted HR, 1.13 (95% CI, 1.00-1.29); absolute excess risk, 14.8 (95% CI, 4.5-25.2) per 1,000 person-years). Compared with T2DM, PPDM was associated with higher risks of mortality from cancer (adjusted HR, 1.44; 95% CI, 1.13-1.83), infectious disease (adjusted HR, 2.52; 95% CI,…

OBJECTIVES: In contrast with other developed nations, life expectancy is decreasing in the United States, in part due to increasing mortality from alcohol-associated liver disease (ALD). Up-to-date estimates of ALD mortality are necessary for setting public health priorities to reverse this concerning trend. We therefore aimed to assess current (2017) estimates of ALD mortality and temporal trends from 1999 to 2017. METHODS: Using national data from the Centers for Disease Control and Prevention, we analyzed stratified ALD mortality rates between 1999 and 2017. We determined the age-adjusted death rates, stratified by sex and categorized by age, race/ethnicity, urbanization, and census region. We also identified statistically significant changes in the annual rate difference (ARD), annual percentage change (APC), and average APC in ALD mortality. RESULTS: In 2017, mortality from ALD was higher than any other year since 1999 with age-adjusted rates of 13.1 per 100,000 (95% confidence interval [CI] 12.9-13.3) in men and 5.6 per 100,000 (95% CI 5.4-5.7) in women. Mortality was highest…

OBJECTIVES: Common variable immunodeficiency (CVID) is associated with a spectrum of autoimmune complications. We studied the prevalence of gastrointestinal (GI) manifestations and infections in patients with CVID. METHODS: Complete clinical data of 132 Finnish patients with CVID (106 probable and 26 possible CVID) followed up between 2007 and 2016 were collected to a structured database. Data on endoscopies, histology, and laboratory studies were retrieved from patient files. RESULTS: Most common referral indications were diarrhea and/or weight loss (47%-67%). Patients with probable CVID had higher fecal calprotectin and α1-antitrypsin and lower blood vitamin B12 than patients with possible CVID. Gastroscopy and colonoscopy were done to 71 (67%) and 63 (59%) patients with probable CVID, respectively. Endoscopies showed that 15% of them had chronic active gastritis and 17% atrophic gastritis and 3% had gastric adenocarcinoma. A celiac sprue-like condition was found in 7 patients (10%), of whom 3 responded to a gluten-free diet. Colonoscopies demonstrated unspecific colitis (14%),…

OBJECTIVES: Crohn's disease (CD) is a chronic relapsing-remitting gut inflammatory disorder with a heterogeneous unpredictable course. Dysbiosis occurs in CD; however, whether microbial dynamics in quiescent CD are instrumental in increasing the risk of a subsequent flare remains undefined. METHODS: We analyzed the long-term dynamics of microbial composition in a prospective observational cohort of patients with quiescent CD (45 cases, 217 samples) over 2 years or until clinical flare occurred, aiming to identify whether changes in the microbiome precede and predict clinical relapse. Machine learning was used to prioritize microbial and clinical factors that discriminate between relapsers and nonrelapsers in the quiescent phase. RESULTS: Patients with CD in clinical, biomarker, and mucosal remission showed significantly reduced microbial richness and increased dysbiosis index compared with healthy controls. Of the 45 patients with quiescent CD, 12 (27%) flared during follow-up. Samples in quiescent patients preceding flare showed significantly reduced abundance of…

OBJECTIVES: Alcohol-associated liver disease is increasing, especially hospitalizations with acute on chronic liver failure and need for liver transplant. We examined trends in prevalence, inhospital mortality, and resource utilization associated with AALD and ACLF in the young. METHODS: The National Inpatient Sample (2006-2014) was queried for hospitalizations with a discharge diagnosis of cirrhosis using the International Classification of Diseases, Ninth Edition, codes. ACLF hospitalization was defined as ≥2 organ failures and stratified by age: young (≤35 years) and older (>35 years). RESULTS: Of 447,090 AALD admissions (16,126 in young) between 2006 and 2014, ACLF occurred in 29,599 (6.6%), of which 1,143 (7.1%) were in young. Compared with older, admissions in young had more women (35% vs 29%), were obese (11% vs 7.6%), were Hispanics (29% vs 18%), have alcoholic hepatitis (AH) (41% vs 17%), and have ACLF grades 2 or 3 (34% vs 25%), P < 0.001 for all. Between 2006 and 2014, ACLF in AALD among young increased from 2.8% to 5.2%, with an AH proportion from 24% to 42%, P < 0.0001…

OBJECTIVES: The nonsystemic antibiotic rifaximin is indicated for irritable bowel syndrome with diarrhea (IBS-D) in adults; however, determinants of response remain unclear. The utility of lactulose breath testing (LBT) in predicting response to rifaximin was examined. METHODS: Adults with IBS-D received open-label rifaximin 550 mg 3 times daily for 2 weeks, followed by a 4-week posttreatment assessment period. Thirteen centers prospectively participated in this substudy. LBT was conducted before (day 1) and after (day 14) therapy (breath samples obtained every 15 minutes; up to 240 minutes). Patient response (decrease from baseline of ≥30% in abdominal pain and ≥50% decrease in frequency of mushy/watery stool), symptom improvement, and the relationship of clinical outcomes to LBT results were assessed. RESULTS: A total of 93 patients were included; 62 (66.7%) had positive baseline LBT results. Overall, 48.4% (45/93) of patients responded to rifaximin; of these, 59.7% (37/62) had a positive baseline LBT vs 25.8% (8/31) with a negative LBT (P = 0.002; odds ratio 4.3, 95% confidence…

There is a growing appreciation for the role of the gut microbiome in human health and disease. Aided by advances in sequencing technologies and analytical methods, recent research has shown the healthy gut microbiome to possess considerable diversity and functional capacity. Dysbiosis of the gut microbiota is believed to be involved in the pathogenesis of not only diseases that primarily affect the gastrointestinal tract but also other less obvious diseases, including neurologic, rheumatologic, metabolic, hepatic, and other illnesses. Chronic immune-mediated inflammatory diseases (IMIDs) represent a group of diseases that share many underlying etiological factors including genetics, aberrant immunological responses, and environmental factors. Gut dysbiosis has been reported to be common to IMIDs as a whole, and much effort is currently being directed toward elucidating microbiome-mediated disease mechanisms and their implications for causality. In this review, we discuss gut microbiome studies in several IMIDs and show how these studies can inform our understanding of the role of…

OBJECTIVES: Rates of surgery for nonmalignant colorectal polyps are increasing in the United States despite evidence that most polyps can be managed endoscopically. We aimed to determine nationally representative estimates and to identify predictors of in-hospital mortality and morbidity after surgery for nonmalignant colorectal polyps. METHODS: Data were analyzed from the National Inpatient Sample for 2005-2014. All discharges for adult patients undergoing surgery for nonmalignant colorectal polyps were identified. Rates of in-hospital mortality and postoperative wound, infectious, urinary, pulmonary, gastrointestinal, or cardiovascular adverse events were calculated. Multivariable logistic regression using survey-weighted data was used to evaluate covariables associated with postoperative mortality and morbidity. RESULTS: An estimated 262,843 surgeries for nonmalignant colorectal polyps were analyzed. In-hospital mortality was 0.8% [95% confidence interval: 0.7%-0.9%] and morbidity was 25.3% [95% confidence interval: 24.2%-26.4%]. Postoperative mortality was associated with open…

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was…

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs…

OBJECTIVES: We compared liver-related mortality by fibrosis severity between 2 types of fatty liver disease (FLD), nonalcoholic FLD (NAFLD) and alcoholic FLD (AFLD), in a large cohort of nonobese and obese individuals. METHODS: A cohort study was performed with 437,828 Korean adults who were followed up for up to 14 years. Steatosis was diagnosed based on ultrasonography; fibrosis severity was determined by the fibrosis 4 (FIB-4) score. Vital status and liver-related deaths were ascertained through linkage to national death records. RESULTS: The prevalence of NAFLD and AFLD was 20.9% and 4.0%, respectively. During 3,145,541.1 person-years of follow-up, 109 liver-related deaths were identified (incidence rate of 3.5 per 10 person-years). When changes in fatty liver status, FIB-4 scores, and confounders during follow-up were updated as time-varying covariates, compared with the reference (absence of both excessive alcohol use and FLD), the multivariable-adjusted hazard ratios with 95% confidence intervals for liver-related mortality among those with low, intermediate, and high FIB-4…

Intragastric balloons (IGBs) are the most widely available endoscopic bariatric therapy for class I and II obesity in the United States. Although simple in application and reversible by nature, these devices may help patients initiate the important first steps in weight loss maintenance, provided that parallel efforts are in motion to prevent weight recidivism. Too often, therapeutic nihilism stems from unrealistic expectations of a given therapy. In the case of IGBs, this sentiment may occur when these interventions are applied in a vacuum and not within the purview of a multidisciplinary program that actively involves dieticians, endocrinologists, gastroenterologists, and surgeons. There is a clear and present need to apply different tactics in the remissive strategy to control the obesity pandemic, more so in a struggling landscape of an ever-widening gap in bridging interventions. With such demand, the IGB is an available tool that could be helpful when correctly implemented. In this exposition, we summarize the current state of IGBs available worldwide, discuss their mechanism…

OBJECTIVES: Differentiating Crohn's disease (CD) from intestinal tuberculosis (ITB) remains a diagnostic challenge. Misdiagnosis carries potential grave implications. We aimed to develop and validate a novel diagnostic nomogram for differentiating them. METHODS: In total, 310 eligible patients were recruited from 6 tertiary inflammatory bowel disease centers. Among them, 212 consecutive patients (143 CD and 69 ITB) were used in the derivation cohort for the establishment of diagnostic equation and nomogram; 7 investigative modalities including clinical manifestations, laboratory results, endoscopic findings, computed tomography enterography features, and histology results were used to derive the diagnostic model and nomogram. Ninety-eight consecutive patients (76 CD and 22 ITB) were included for validation of the diagnostic model. RESULTS: Eight out of total 79 parameters were identified as valuable parameters used for establishing diagnostic equations. Two regression models were built based on 7 differential variables: age, transverse ulcer, rectum involvement, skipped involvement…

OBJECTIVES: Combined hepatocellular cholangiocarcinoma (CHC) is a rare form of primary liver cancer with features of hepatocellular carcinoma and cholangiocarcinoma. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with CHC. METHODS: Data on CHC between 2004 and 2014 were extracted from the Surveillance, Epidemiology, and End Results Registry and analyzed. RESULTS: Five hundred twenty-nine patients with CHC were identified; 367 were male. Median age at diagnosis was 62.5 ± 12 years. The overall incidence of CHC between 2004 and 2014 was 0.05 per 100,000 per year. Incidence increased with age, with the highest incidence in men occurring between 60 and 64 years and 75-79 years for women. Women had a higher incidence of CHC compared to men (0.08 vs 0.03 per 100,000 per year). Most tumors were poorly differentiated (30.8%) while the most common stage at presentation was stage 4 (26.8%). 39.5% of these tumors were resected while 6.8% received radiation and 34% received chemotherapy. One- and 5-year…

OBJECTIVES: Although low fiber intake has been considered a risk factor for diverticulitis, prospective evidence is limited in women despite having a disproportionate burden of disease, with little known about variation in the protective effects according to food sources. We assessed the associations of intakes of fiber and major food sources of fiber including fruits and vegetables with risk of diverticulitis in a large cohort of women. METHODS: We followed 50,019 women in the Nurses' Health Study (1990-2014) who were aged 43-70 years and free of diverticulitis, cancer, and inflammatory bowel disease at baseline. Incident diverticulitis was identified through self-report with validity confirmed by review of medical records. RESULTS: We documented 4,343 incident cases of diverticulitis, encompassing 1,106,402 person-years of follow-up. Compared with participants in the lowest quintile, the multivariable hazard ratio of diverticulitis in the highest quintile of total fiber intake was 0.86 (95% confidence interval: 0.78-0.95; P-trend = 0.002). Fiber from fruits and cereals, but not…

INTRODUCTION: Adherence to a gluten-free (GF) diet is the mainstay of therapy for celiac disease. Until now, those wishing to avoid gluten in restaurants had to rely on menu labels, word of mouth, intuition, and restaurant workers' advice, with a relative dearth of supporting data. We used crowd-sourced data from users of a portable gluten detection device to estimate rates of, and identify risk factors for, gluten contamination of supposed GF restaurant foods. METHODS: We analyzed data from a portable gluten detection device (Nima), collected across the United States during an 18-month period by users who opted to share the results of their point-of-care tests. Data were sorted by region, time of day, median household income in the restaurant's vicinity, restaurant genre, and food items. We used the χ test for bivariate analysis and multiple logistic regression for multivariate analysis to identify predictors of gluten detection in restaurant food. RESULTS: There were 5,624 tests, performed by 804 users, in the examined period. Gluten was detected in 32% of GF labeled foods. Rates…

OBJECTIVES: Minimal hepatic encephalopathy (MHE) is epidemic in cirrhosis, but testing strategies often have poor concordance. Altered gut/salivary microbiota occur in cirrhosis and could be related to MHE. Our aim was to determine microbial signatures of individual cognitive tests and define the role of microbiota in the diagnosis of MHE. METHODS: Outpatients with cirrhosis underwent stool collection and MHE testing with psychometric hepatic encephalopathy score (PHES), inhibitory control test, and EncephalApp Stroop. A subset provided saliva samples. Minimal hepatic encephalopathy diagnosis/concordance between tests was compared. Stool/salivary microbiota were analyzed using 16srRNA sequencing. Microbial profiles were compared between patients with/without MHE on individual tests. Logistic regression was used to evaluate clinical and microbial predictors of MHE diagnosis. RESULTS: Two hundred forty-seven patients with cirrhosis (123 prior overt HE, MELD 13) underwent stool collection and PHES testing; 175 underwent inhibitory control test and 125 underwent Stroop testing. One…

INTRODUCTION: Although hemorrhoids are a common indication for seeking health care, there are no contemporary estimates of burden and cost. We examined data from an administrative claims database to estimate health care use and aggregate costs. METHODS: We conducted a cross-sectional study using the MarketScan Commercial Claims and Encounters Database for 2014. The analysis included 18.9 million individuals who were aged 18-64 and continuously enrolled with prescription coverage. Outpatient hemorrhoid claims were captured using the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes in the first position, as well as Common Procedural Terminology codes. Prescription medications were identified using National Drug Codes. Annual prevalence and costs were determined by summing gross payments for prescription medications, physician encounters, and facility costs. We used validated weights to standardize annual cost estimates to the US employer-insured population. RESULTS: In 2014, we identified 227,638 individuals with at least one outpatient…

OBJECTIVES: Premature activation of the digestive protease trypsin within the pancreatic parenchyma is a critical factor in the pathogenesis of pancreatitis. Alterations in genes that affect intrapancreatic trypsin activity are associated with chronic pancreatitis (CP). Recently, carboxyl ester lipase emerged as a trypsin-independent risk gene. Here, we evaluated pancreatic lipase (PNLIP) as a potential novel susceptibility gene for CP. METHODS: We analyzed all 13 PNLIP exons in 429 nonalcoholic patients with CP and 600 control subjects from Germany, in 632 patients and 957 controls from France, and in 223 patients and 1,070 controls from Japan by DNA sequencing. Additionally, we analyzed selected exons in further 545 patients with CP and 1,849 controls originating from Germany, United States, and India. We assessed the cellular secretion, lipase activity, and proteolytic stability of recombinant PNLIP variants. RESULTS: In the German discovery cohort, 8/429 (1.9%) patients and 2/600 (0.3%) controls carried a PNLIP missense variant (P = 0.02, odds ratio [OR] = 5.7, 95% confidence…

OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP. METHODS: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol). RESULTS: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3…

Sclerosing mesenteritis is a rare non-neoplastic disorder characterized by fat necrosis, chronic inflammation, and fibrosis typically of the small bowel mesentery. Our understanding of this disorder is limited by its rarity as well as inconsistent terminology used across the literature. While prior abdominal surgery or trauma, autoimmunity, infection, ischemia, and malignancy have been suggested to be involved in the pathogenesis of the disorder, it remains poorly understood. The clinical course of sclerosing mesenteritis is generally benign with a large proportion of patients diagnosed incidentally on imaging obtained for other indications. In a subset of patients, symptoms may arise from a mass effect on the bowel, lymphatics, or vasculature resulting in bowel obstruction, chylous ascites, or mesenteric ischemia. Symptomatic patients should be treated with a combination of corticosteroid and tamoxifen as first-line therapy based on retrospective case series and experience in other fibrosing disorders. Surgical intervention may be required in those with persistent obstruction…

OBJECTIVES: Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis. METHODS: North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality. RESULTS: The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant…

OBJECTIVES: Despite encouraging data gathered in inflammatory bowel diseases (IBD) patients, Vedolizumabs' (VDZ) safety profile in pregnancy is not established. DESIGN: Data of 330 consecutive pregnancies with IBD was prospectively collected. RESULTS: Women with IBD were treated with: VDZ (n = 24), anti-tumor necrosis factors (n = 82) or conventional therapy (n = 224). Gravidity and parity were similar among the 3 groups. The VDZ group was comprised mostly of Crohn's disease patients who were all not naïve to biological treatment. They had significantly higher conception rates during active disease (P < 0.05), with fewer flares during pregnancy. DISCUSSION: Although further study is needed, VDZ appears of low risk during pregnancy.

OBJECTIVES: Little is known about how reports on the adverse effects of proton pump inhibitors (PPIs) impact patients' perceptions of these drugs and medication use. We sought to determine patients' level of concern about PPI adverse effects and its association with attempts to discontinue these drugs. METHODS: This study is an online survey of US adults who use PPIs for gastroesophageal reflux disease. Topics included awareness of and concern about PPI adverse effects, prior discussion with providers, and attempts to stop PPI because of concern about adverse effects. For the primary analysis, we used logistic regression to identify associations between having attempted to stop PPI and concern about PPI-related adverse effects, a provider's recommendation to stop, risk of upper gastrointestinal bleeding (UGIB), age, and gender. RESULTS: Among 755 patient participants, mean age was 49 years (s.d. 16), 71% were women, and 24% were at high risk of UGIB. Twenty percent of patients were able to write in ≥1 reported adverse effect, and 46% endorsed awareness of ≥1 adverse effect when…

Rheumatological diseases (RDs) represent a diverse group of diseases that are inherited or related to environmental factors. RDs frequently affect the gastrointestinal (GI) tract, and gastroenterologists are often asked to evaluate patients with symptoms thought to represent an underlying or coexisting RD. GI manifestations of RDs vary based on the organ involved as well as the extent and duration of involvement. Although most manifestations of RD are nonspecific and not life-threatening, the chronicity and severity of symptoms can be debilitating and may lead to serious injury. This narrative review discusses the most common RD encountered by gastroenterologists: systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis/polymyositis, rheumatoid arthritis, Sjögren syndrome, overlap syndromes, mixed connective tissue disease, Ehlers-Danlos syndromes, and other vasculitides. Each section begins with a brief overview of the condition, followed by a discussion of the etiopathophysiology, physical examination findings, GI manifestations, diagnostic tools (i.e.,…

Pancreatic steatosis is an emerging clinical entity whose pathophysiology, natural history, and long-term complications are poorly characterized in the current literature. Epidemiological and prospective studies have described prevalence rates between 16% and 35%. Although the natural history is not well known, there are strong associations with obesity, metabolic syndrome, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Ectopic fat accumulation of the pancreas can cause chronic, low-grade inflammation from adipocytokine imbalances that involve beta cells and acinar cells. This mechanism can lead to pancreatic endocrine and exocrine dysfunction and initiate carcinogenesis. Although it is associated with morbid conditions, pancreatic steatosis may be amendable to treatment with a healthy diet, less meat consumption, exercise, and smoking cessation. Pancreatic steatosis should factor into clinical decision-making and prognostication of patients with pancreatic and systemic disease. This review seeks to describe the pathophysiology, natural history, diagnosis, and…

OBJECTIVES: Adherence to a healthy diet has been associated with a reduced risk of type 2 diabetes (T2D). Hepatocellular carcinoma (HCC) may have overlapping mechanisms with T2D, such as inflammation and insulin resistance. Thus, we examined the association between a previously developed T2D prevention dietary pattern and HCC risk. METHODS: We followed 87,943 women in the Nurses' Health Study and 49,665 men in the Health Professionals Follow-up Study for up to 32 years. The dietary diabetes risk reduction score, which includes dietary glycemic index, cereal fiber, ratio of polyunsaturated to saturated fats, trans fat, sugar-sweetened beverages, nuts, coffee, and red and processed meats, was obtained using validated food frequency questionnaires and updated every 4 years. The Cox proportional hazards regression model was used to calculate multivariable hazard ratios and confidence intervals (95% CIs). RESULTS: During over 1.9 million person-years, a total of 160 incident HCC cases were identified. The dietary diabetes risk reduction score was associated with a lower risk of HCC (top…

OBJECTIVES: Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. METHODS: Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). RESULTS: Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with…

INTRODUCTION: Alterations in the immune system can result in alanine aminotransferase (ALT) flares either during pregnancy or after delivery in women with chronic hepatitis B virus (HBV) infection. The aim of this study was to prospectively assess changes in serum biochemical and virological markers of HBV infection during and after pregnancy in a large North American cohort of pregnant women with chronic HBV. METHODS: Adult pregnant women enrolled in the Hepatitis B Research Network between 2011 and 2016 were included. Serum ALT values and HBV DNA viral levels were obtained at <28 weeks and >28 weeks of gestation and <16 weeks, 16-31 weeks, and 32-48 weeks postpartum. Outcomes of ALT flares included severity, duration, and initiation of antiviral therapy. RESULTS: Among the 158 pregnant women with chronic HBV, the median age was 33 years, 73% were Asian, and 63% were hepatitis B e antigen (HBeAg) negative. The median HBV DNA level was substantially higher in the HBeAg-positive vs HBeAg-negative women (1.3 × 10 vs 343 IU/mL), but serum ALT levels at their first study visit were…

INTRODUCTION: Detailed recommendations and guidelines for acute pancreatitis (AP) management currently exist. However, quality indicators (QIs) are required to measure performance in health care. The goal of the Acute Pancreatitis Task Force on Quality was to formally develop QIs for the management of patients with known or suspected AP using a modified version of the RAND/UCLA Appropriateness Methodology. METHODS: A multidisciplinary expert panel composed of physicians (gastroenterologists, hospitalists, and surgeons) who are acknowledged leaders in their specialties and who represent geographic and practice setting diversity was convened. A literature review was conducted, and a list of proposed QIs was developed. In 3 rounds, panelists reviewed literature, modified QIs, and rated them on the basis of scientific evidence, bias, interpretability, validity, necessity, and proposed performance targets. RESULTS: Supporting literature and a list of 71 proposed QIs across 10 AP domains (Diagnosis, Etiology, Initial Assessment and Risk Stratification, etc.) were sent to the expert panel…

OBJECTIVES: Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials and examined the relationship between histologic and endoscopic outcomes. METHODS: MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for randomized controlled trials of aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random-effect or fixed-effect models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. RESULTS: Seventy-four studies (68 induction and 7 maintenance) were identified. Topical aminosalicylate enemas…

OBJECTIVES: Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are 2 commonly ordered liver function tests, and ALT has long been considered more liver-specific than AST. Between the 2, the one which is better in predicting liver or non-liver-related mortality remains unsettled. METHODS: The cohort, 416,122 adults, came from a self-paying comprehensive health surveillance program during 1994-2008 and was followed up till 2008. Mortality came from National Death Index, with 10,412 deaths identified. Hazard ratios (HRs), computed by Cox model, and life expectancy, by life table method, were presented for 5 levels of AST and ALT with elevated AST or ALT defined as ≥40 IU/L. Liver disease included liver cancer and other liver conditions. RESULTS: There were 3 times more elevated ALT (15.4%) than AST (5.7%). However, those with elevated AST had higher mortality for all-cause (HR = 2.44), for liver disease (HR = 27.2), and for liver cancer (HR = 47.6) than its ALT counterparts (HR = 1.69, 10.8, and 20.2, respectively). Elevated AST also lost more years of life…

OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%.…

OBJECTIVES: Up to 20% of patients with refractory gastroesophageal reflux disease (GERD) might have postprandial rumination. The aim of this study was to distinguish persistent GERD-related postprandial regurgitation from rumination in patients with refractory GERD undergoing ambulatory multichannel intraluminal impedance-pH (MII-pH) monitoring. METHODS: We first characterized 24-hour and postprandial MII-pH patterns in 28 consecutive patients with confirmed rumination syndrome (positive clinical and high-resolution manometry/impedance). We compared such MII-pH patterns with those from 30 patients with typical GERD symptoms (10 nonerosive reflux disease, 10 hyperactive esophagus, and 10 functional heartburn) and 27 healthy controls. Using ROC curves, we selected the best MII-pH parameters to prepare an MII-pH rumination score. We prospectively tested the performance of the new MII-pH rumination score in 26 consecutive patients with refractory GERD (predominant regurgitation). RESULTS: Compared with GERD controls, patients with rumination were more often females, younger, and had…

OBJECTIVES: Irritable bowel syndrome with diarrhea (IBS-D) is a functional gastrointestinal disorder with limited effective treatment options. We evaluated the efficacy and safety of eluxadoline in patients with IBS-D who reported inadequate symptom control with prior loperamide. METHODS: Three hundred forty-six adults with IBS-D (Rome III criteria) were randomly assigned to placebo or eluxadoline 100 mg twice daily for 12 weeks. Patients recorded daily IBS-D symptoms, including worst abdominal pain (WAP) and stool consistency (through Bristol Stool Scale). The primary endpoint was proportion of composite responders, defined as patients who met daily composite response criteria (≥40% WAP improvement and <5 Bristol Stool Scale score) for at least 50% of treatment days, and recorded ≥60 days of diary entries over the 12-week period. RESULTS: Over 12 weeks, a significantly greater proportion of eluxadoline patients achieved the primary composite responder endpoint compared to placebo (22.7% vs 10.3%, P = 0.002), and component endpoints of improvements in stool consistency (27.9% vs…

OBJECTIVES: To determine the association between the amount of gluten intake in childhood and later celiac disease (CD), for which data are currently scarce. METHODS: The prospective Diabetes Autoimmunity Study in the Young cohort includes 1875 at-risk children with annual estimates of gluten intake (grams/d) from age 1 year. From 1993 through January 2017, 161 children, using repeated tissue transglutaminase (tTGA) screening, were identified with CD autoimmunity (CDA) and persistent tTGA positivity; of these children, 85 fulfilled CD criteria of biopsy-verified histopathology or persistently high tTGA levels. Cox regression, modeling gluten intake between ages 1 and 2 years (i.e., in 1-year-olds), and joint modeling of cumulative gluten intake throughout childhood were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS: Children in the highest third of gluten intake between the ages of 1 and 2 years had a 2-fold greater hazard of CDA (aHR 2.17; 95% confidence interval [CI], 1.22-3.88; P value = 0.01) and CD (aHR 1.96; 95% CI, 0.90-4.24; P value = 0.09) than…

OBJECTIVES: As the prevalence of nonalcoholic steatohepatitis (NASH) in the elderly population increases, healthcare resource utilization (HCRU) and costs are also predicted to rise substantially. METHODS: This retrospective, observational cohort study used the Medicare 20% sample data set to evaluate the impact of NASH severity on HCRU and costs over 8 years (2007-2015). The sample included 255,681 patients with nonalcoholic fatty liver disease (NAFLD)/NASH: 185,407 (72.5%) with NAFLD/NASH and no further progression to advanced liver disease, 3,454 (1.3%) with compensated cirrhosis (CC), 65,926 (25.8%) with decompensated cirrhosis (DCC), 473 (0.2%) with liver transplant (LT), and 421 (0.2%) with hepatocellular carcinoma (HCC). RESULTS: Rates of comorbid diabetes, hypertension, hyperlipidemia, and cardiovascular disease were significantly higher in patients with CC or more severe liver disease compared with NAFLD/NASH and no progression. The annual mean number of all-cause healthcare visits increased from 32.1 for NAFLD/NASH with no progression to 37.3 for CC, 59.8 for DCC, 74.1 for…

OBJECTIVES: Although chromoendoscopy is currently the recommended mode of surveillance in patients with long-standing ulcerative colitis, it is technically challenging and requires a long procedure time. The aim of this study was to compare the dysplasia detection rate of high-definition white light endoscopy with random biopsy (HDWL-R) vs high-definition chromoendoscopy with targeted biopsy (HDCE-T). METHODS: This was a multicenter, prospective randomized controlled trial involving 9 tertiary teaching hospitals in South Korea. A total of 210 patients with long-standing ulcerative colitis were randomized to undergo either the HDWL-R group (n = 102) or HDCE-T group (n = 108). The detection rates of colitis-associated dysplasia (CAD) or all colorectal neoplasia from each trial arm were compared. RESULTS: There was no significant difference in the CAD detection rate between HDCE-T and HDWL-R groups (4/102, 3.9% vs 6/108, 5.6%, P = 0.749). However, HDCE-T showed a trend toward improved colorectal neoplasia detection compared with HDWL-R (21/102, 20.6% vs 13/108, 12.0%, P = 0.093). The…

OBJECTIVES: Small intestinal bacterial overgrowth (SIBO) is often present in patients with chronic pancreatitis (CP) with persistent steatorrhea, despite pancreatic enzyme replacement therapy. Overall prevalence of SIBO, diagnosed by glucose breath test (GBT), varies between 0% and 40% but 0%-21% in those without upper gastrointestinal (GI) surgery. We investigated the prevalence and nonsurgical independent predictors of SIBO in CP without upper GI surgery. METHODS: Two hundred seventy-three patients ≥18 years old had a presumptive diagnosis of CP and a GBT between 1989 and 2017. We defined CP by Mayo score (0-16) ≥4 and a positive GBT for SIBO by Rome consensus criteria and retrospectively collected data for 5 a priori variables (age, opiates, alcohol use, diabetes mellitus (DM), gastroparesis) and 41 investigational variables (demographics, GI symptoms, comorbidities, CP etiologies and cofactors, CP symptom duration, Mayo score and nondiabetes components, and biochemical variables). RESULTS: Ninety-eight of 273 patients had definite CP and 40.8% had SIBO. Five of 46 variables…

Most gastrointestinal (GI) subepithelial tumors (SETs) are identified incidentally during endoscopic examination and are located in the stomach. Some SETs are malignant or have the potential to become malignant. Tumors originating from deeper layers, such as the muscularis propria or serosa, are not easy to diagnose and resect. Current guidelines recommend yearly endoscopic surveillance of SETs smaller than 2 cm. This recommendation may not be cost-effective in managing GI SETs. Endoscopic resection results not only in obtaining sufficient tissue for pathological diagnosis but also in resection and curing the tumor. Many different endoscopic methods for resection of GI SETs have been published in the literature. To avoid confusion, we have divided these methods into standard endoscopic submucosal dissection, modified endoscopic submucosal dissection, submucosal tunneling endoscopic resection, and nonexposed and exposed endoscopic full-thickness resection. These procedures offer less invasive approaches than surgery for resection of GI SETs and may be the most cost-effective in…

OBJECTIVES: Cardiovascular (CV) disease is the top cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Female sex is protective against CV disease. We aimed to determine whether female sex remains a protective factor against CV disease (myocardial infarction, angina, and stroke) in NAFLD. METHODS: We identified all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 and selected an age- and sex-matched (1:4) referent cohort from the general population. NAFLD was ascertained using a code-based algorithm with high validity tested by medical record review. The impact of female sex on incident CV events was examined using Cox proportional hazards regression analysis stratified by standard clinical risk factors. RESULTS: A total of 3,869 NAFLD and 15,209 age- and sex-matched referent subjects were identified. After a median follow-up time of 7 (range 1-20) years, 3,851 CV events were recorded. Female sex was protective for ischemic CV events in the general population (hazard ratio = 0.71, 95% confidence interval 0.62-0.80, P < 0.001),…

INTRODUCTION: Although there is substantial evidence suggesting poor health-related quality of life (HRQL) in patients with chronic hepatitis C (CHC), similar data in nonalcoholic steatohepatitis (NASH) have not been fully assessed. The aim is to compare HRQL scores in patients with CHC to those with NASH. METHODS: Matched patients with advanced fibrosis (bridging fibrosis and compensated cirrhosis) due to CHC and NASH completed Short Form-36 (SF-36) questionnaire, Chronic Liver Disease Questionnaire (CLDQ), and Work Productivity and Activity Instrument questionnaire. RESULTS: We included 1,338 patients with NASH with advanced fibrosis (mean age 57.2 years, 47% men, 55% cirrhosis) and 1,338 matched patients with CHC. Patients with CHC and NASH had similar rates of employment and psychiatric disorders (P > 0.05). As expected, patients with NASH had higher body mass index (mean 33.7 vs 27.6) and more type 2 diabetes (74% vs 16%) (all P < 0.01). Patients with NASH had significantly lower HRQL scores related to physical health: Physical Functioning, Bodily Pain, General Health,…

Cholestatic liver diseases encompass a broad spectrum of pathologies, with the core injury occurring at the level of cholangiocytes and progressing to hepatic fibrosis and liver dysfunction. Primary biliary cholangitis and primary sclerosing cholangitis are the most significant progressive cholangiopathies in adults. Although rare, they commonly evolve to liver failure and need for liver transplantation. Despite recent advances in the basic knowledge of these cholangiopathies, the pathogenesis is still elusive. Targeted treatments to prevent disease progression and to preclude malignancy are not yet available. This review will address the general clinical features of both diseases, analyze their commonalities and differences, and provide a state-of-the art overview of the currently available therapeutics.

INTRODUCTION: Ammonia levels are used to assess hepatic encephalopathy, but their levels are highly variable in clinical practice. METHODS: We studied factors associated with variation in ammonia values in cirrhotic patients without previous hepatic encephalopathy and healthy volunteers (HVs). RESULTS: Ammonia increased by 12% and 18% at 1 and 2 hour, respectively, after a protein meal in 64 cirrhotic patients (P < 0.001). In 237 HVs, ammonia levels varied significantly between sites (P < 0.0001). New site-specific ammonia upper limits based on HV levels using a strict analysis protocol differed from routinely used values. Correlation between paired fresh samples was high (r = 0.83) but modest between fresh and frozen samples (r = 0.62). DISCUSSION: Sample handling, processing, and protein intake impact ammonia levels across sites.

Involvement of the gastrointestinal (GI) tract is an infrequent extrathoracic presentation of sarcoidosis. We reviewed 305 cases of GI involvement reported in 238 patients, in whom GI sarcoidosis was the first sign of the disease in half the cases. The disease does not affect the GI tract uniformly, with a clear oral-anal gradient (80% of reported cases involved the esophagus, stomach, and duodenum). Clinicopathological mechanisms of damage may include diffuse mucosal infiltration, endoluminal exophytic lesions, involvement of the myenteric plexus, and extrinsic compressions. Ten percent of patients presented with asymptomatic or subclinical disease found on endoscopy. The diagnosis is relevant clinically because 22% of cases reviewed presented as life threatening. In addition, initial clinical/endoscopic findings may be highly suggestive of GI cancer. The therapeutic approach is heterogeneous and included wait-and-see or symptomatic approaches, glucocorticoid/immunosuppressive therapy, and surgery. Sarcoidosis of the gut is a heterogeneous, potentially life-threatening condition…

OBJECTIVES: Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE). METHODS: Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy. RESULTS: One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than…

INTRODUCTION: Obesity has been associated with liver fibrosis, yet guidelines do not emphasize it as an independent risk factor in which to have a high index of suspicion of advanced disease. We aimed to elucidate the effect of a raised body mass index on the risk of liver disease using data from a community risk stratification pathway. METHODS: We prospectively recruited patients from a primary care practice with hazardous alcohol use and/or type 2 diabetes and/or obesity. Subjects were invited for a transient elastography reading. A threshold of ≥8.0 kPa defined an elevated reading consistent with clinically significant liver disease. RESULTS: Five hundred seventy-six patients participated in the pathway; of which, 533 patients had a reliable reading and 66 (12.4%) had an elevated reading. Thirty-one percent of patients with an elevated reading had obesity as their only risk factor. The proportion of patients with an elevated reading was similar among those with obesity (8.9%) to patients with more recognized solitary risk factors (type 2 diabetes 10.8%; hazardous alcohol use…

INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard…

OBJECTIVES: Avoiding fibrostenotic complications is of paramount concern in the management of Crohn's disease (CD). We sought to investigate the association of candidate biomarkers of fibrosis collected at diagnosis with the future development of fibrostenotic CD. METHODS: Using the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort, a multicenter prospective observational pediatric inception cohort, subjects with an inflammatory phenotype (B1) at diagnosis who later converted to a stricturing phenotype (B2) within 3 years were compared with those who remained B1. Serum collected at diagnosis underwent both parallel reaction monitoring-targeted proteomic analysis and conventional enzyme-linked immunosorbent assay for 10 candidate biomarkers of intestinal fibrosis. Cox proportional hazard regression was used for multivariable analysis of time-dependent outcomes. RESULTS: In 116 subjects 58 subjects with verified B1 phenotype at diagnosis who later converted to B2 disease were compared with…

INTRODUCTION: Guidelines recommend that patients with non-dysplastic Barrett's esophagus (NDBE) undergo surveillance endoscopy every 3-5 years. Using a national registry, we assessed compliance to recommended surveillance intervals in patients with NDBE and identified factors associated with compliance. METHODS: We analyzed data from the GI Quality Improvement Consortium registry. Data abstracted include procedure indication, demographics, endoscopy/pathology results, and recommendations for future endoscopy. Patients with an indication of Barrett's esophagus (BE) screening or surveillance, or an endoscopic finding of BE, with non-dysplastic intestinal metaplasia on pathological examination, were included. Compliance was defined as a recommendation to undergo subsequent endoscopy between 3 and 5 years. Multivariate logistic regression was conducted to assess variables associated with compliance. RESULTS: Of 786,712 endoscopies assessed, 58,709 (7.5%) endoscopies in 53,541 patients met inclusion criteria (mean age 61.3 years, 60.4% men, 90.2% white, mean BE length was 2.3 cm). Most…

OBJECTIVES: To determine the effectiveness of surveillance colonoscopy (SC) and optimize its use by assessing real-world surgically resected cases of ulcerative colitis (UC)-associated colorectal cancer (CRC) and dysplasia. METHODS: Clinicopathological data of 406 (238 CRC and 168 dysplasia) patients who underwent surgical resection in 10 UC specialized institutions were retrospectively reviewed. The overall survival (OS) rates were compared between the SC and non-SC groups. The incidence of and risk factors for early-onset CRC (<8 years after UC onset) were identified. The distribution of CRC lesions was also assessed. RESULTS: Cancer stages were significantly more advanced in the non-SC group than in the SC group (P < 0.001). The patients in the SC group showed significantly better OS than those in the non-SC group (5-year OS: 89% vs 70%; log-rank test: P = 0.001). Seventeen percent of patients developed CRC within 8 years after UC onset. The age at UC onset was a risk factor and a good predictor of early-onset CRC (<8 years) (P < 0.01; AUC: 0.85). The most common sites of CRC…

OBJECTIVES: National societies provide little guidance regarding which colonoscopy bowel preps are best tolerated and most effective; this reflects a lack of comparative effectiveness studies that directly evaluate the available preps in a "real-world" setting. To address this gap, we conducted a prospective, commercially unfunded comparative effectiveness study of currently available bowel preps and measured their impact on bowel cleansing. METHODS: We included patients aged ≥18 years, who presented for an outpatient colonoscopy at a large medical center serving more than 70 academic and community-based endoscopists who are free to prescribe the bowel prep of their choice. The primary outcome was bowel cleansing quality as measured by the Boston Bowel Preparation Scale. We performed regression models with random effects on the outcomes to adjust for confounding. RESULTS: Approximately 4,339 colonoscopies were performed by 75 endoscopists. Magnesium citrate, MiraLAX with Gatorade, MoviPrep, OsmoPrep, Prepopik/Clenpiq, and Suprep all had significantly higher prep tolerability…

INTRODUCTION: Most studies on fractures in inflammatory bowel disease (IBD) are based on patients from tertiary centers or patients followed up before the introduction of immunomodulators or biologics. In addition, the role of corticosteroids in fracture risk has rarely been examined. METHODS: We conducted a nationwide population-based cohort study of 83,435 patients with incident IBD (ulcerative colitis [UC]: n = 50,162, Crohn's disease [CD]: n = 26,763, and IBD unclassified: 6,510) and 825,817 reference individuals from 1964 to 2014. Using multivariable Cox regression, we estimated hazard ratios (HRs) for hip fracture and any fracture and the association with cumulative corticosteroid exposure. RESULTS: During 1,225,415 person-years of follow-up in patients with IBD, there were 2,491 first-time hip fractures (203/100,000 person-years) compared with 20,583 hip fractures during 12,405,642 person-years in reference individuals (159/100,000 person-years). This corresponded to an HR of 1.42 (95% confidence interval [CI] = 1.36-1.48). The risk for hip fracture was higher in CD compared…

OBJECTIVES: Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma. METHODS: This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 sex hormones. RESULTS: Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR = 0.44, 95% confidence interval [CI] 0.22-0.88), testosterone:estradiol ratio (OR = 0.37, 95% CI 0.19-0.72), and luteinizing hormone (OR = 0.50, 95% CI 0.30-0.98), after adjustment for tobacco smoking and physical…

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients…

OBJECTIVES: Magnetic resonance (MR) risk scores and liver stiffness (LS) have individually been shown to predict clinical outcomes in primary sclerosing cholangitis (PSC). The aim of this study was to assess their complementary prognostic value. METHODS: Patients with PSC from 3 European centers with a 3-dimensional MR cholangiography available for central reviewing and a valid LS measurement assessed by vibration-controlled transient elastography by FibroScan performed within a 6-month interval were included in a longitudinal retrospective study. The MR score (Anali) without gadolinium (Gd) was calculated according to the formula: (1 × dilatation of intrahepatic bile ducts) + (2 × dysmorphy) + (1 × portal hypertension). The primary end point was survival without liver transplantation or cirrhosis decompensation. The prognostic values of LS and Anali score without Gd were assessed using Cox proportional hazard models. RESULTS: One hundred sixty-two patients were included. Over a total follow-up of 753 patient-years, 40 patients experienced an adverse outcome (4 liver…

INTRODUCTION: Split-dose bowel preparation leads to superior colon cleansing for colonoscopy. However, the magnitude of benefit in detecting colonic polyps is uncertain. We performed a systematic review to synthesize the data on whether using a split-dose bowel preparation regimen improves the detection of polyps when compared with other dosing methods or regimen products. METHODS: We searched MEDLINE, EMBASE, and CENTRAL databases (from the inception to June 2017) for randomized controlled trials that assessed the following: split-dose vs day-before, split-dose vs same-day (as colonoscopy), or different types of split-dose regimens for patients undergoing colonoscopy. We excluded studies limited to inpatients, children, or individuals with inflammatory bowel disease. We compared the number of patients undergoing colonoscopy with recorded detection of polyps, adenomas, advanced adenomas, sessile serrated polyps (SSPs), right colonic adenomas, right colonic polyps, or right colonic SSPs. RESULTS: Twenty-eight trials fulfilled the inclusion criteria (8,842 participants). Of the seven…

OBJECTIVES: Endoscopic sleeve gastroplasty (ESG) uses full-thickness sutures that restrict the stomach to a sleeve-like configuration. There is no published evidence on endoscopic tissue apposition techniques in pediatric patients. In this article, we report our ESG experience with the first 109 pediatric patients with obesity who underwent ESG under our care. METHODS: ESG was offered as a day-case procedure under a standardized protocol and clinical pathway that included surgical, medical, and endoscopic modalities for the treatment of pediatric and adult obesity. ClinicalTrials.gov Identifier: NCT03778697. RESULTS: The 109 patients in this study had a baseline body mass index and age of 33.0 ± 4.7 and 17.6 ± 2.2 (range: 10-21) years, respectively. Ninety-nine (90.8%) were females. The mean procedure time was 61 ± 19 minutes. The mean % total weight loss at 6, 12, 18, and 24 months was 14.4% ± 6.5%, 16.2% ± 8.3%, 15.4% ± 9.2%, and 13.7% ± 8.0%, respectively. Fourteen adolescents visited the ambulatory clinic for analgesia. One patient (aged 19.8 years) requested removal of…

OBJECTIVES: The ideal analgesic is not known for patients with acute pancreatitis (AP). Concerns have been raised about serious adverse effects of opioid analgesics increasing the severity of AP. We hypothesized that nonsteroidal anti-inflammatory drugs might be better analgesics because of their anti-inflammatory effect. Our objective was to compare pentazocine, an opioid, and diclofenac, a nonsteroidal anti-inflammatory drug, for adequate analgesia in patients with AP. METHODS: In a double-blind randomized controlled trial, patients with AP were randomized to either intravenous diclofenac 75 mg or pentazocine 30 mg. Fentanyl was given as a rescue analgesic through a patient-controlled analgesia pump. Primary outcome was pain relief measured objectively by the dose of fentanyl required as the rescue analgesic, pain-free period, and numbers of effective and ineffective demands of fentanyl. Secondary outcome was adverse events. RESULTS: Fifty patients were randomized, 24 to the pentazocine group and 26 to the diclofenac group. Baseline characteristics were comparable between the…

OBJECTIVES: Cardiac dysfunction has been implicated in the genesis of hepatorenal syndrome (HRS). It is unclear whether a low cardiac output (CO) or attenuated contractile response to hemodynamic stress can predict its occurrence. We studied cardiovascular hemodynamics in cirrhosis and assessed whether a diminished cardiac reserve with stress testing predicted the development of HRS on follow-up. METHODS: Consecutive patients undergoing liver transplant workup with dobutamine stress echocardiography (DSE) were included. CO was measured at baseline and during low-dose dobutamine infusion at 10 μg/kg/min. HRS was diagnosed using guideline-based criteria. RESULTS: A total of 560 patients underwent DSE, of whom 488 were included after preliminary assessment. There were 64 (13.1%) patients with established HRS. The HRS cohort had a higher baseline CO (8.0 ± 2 vs 6.9 ± 2 L/min; P < 0.001) and demonstrated a blunted response to low-dose dobutamine (ΔCO 29 ± 22% vs 44 ± 32%, P < 0.001) driven primarily by inotropic incompetence. Optimal cutpoint for ΔCO in patients with HRS was determined…

INTRODUCTION: Rectal indomethacin and topical spray of epinephrine have separately shown efficacy in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of indomethacin and topical spray of epinephrine on the duodenal papillae would further reduce PEP than when indomethacin was used alone. METHODS: We conducted a comparative effectiveness, multicenter, double-blinded, randomized trial of rectal indomethacin alone vs a combination of rectal indomethacin and topical spray of epinephrine for the prevention of PEP in high-risk patients. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP. A 2-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone vs the combination group. RESULTS: A total of 960 patients (mean age 52.33 ± 14.96 years; 551 [57.4%] females) were randomized and 959 completed follow-up. The baseline demographic and clinical characteristics were similar…

INTRODUCTION: Despite sleeve gastrectomy becoming the most common surgical weight loss procedure, weight loss mechanisms remain less clear. The primary aim of this study was to perform a structured systematic review and meta-analysis of all eligible studies to evaluate changes in various gut hormone levels in patients following sleeve gastrectomy. METHODS: Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through April 1, 2019 in accordance with PRISMA and MOOSE guidelines. Measured outcomes included pre- and post-operative hormones: fasting ghrelin, post-prandial glucagon-like peptide-1 (GLP-1), post-prandial peptide YY (PYY), and fasting gastric inhibitory peptide (GIP) levels. Hedge’s g was used to determine pooled effect size and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed with Cochran Q test and I 2 statistics. Study quality was evaluated with the Newcastle-Ottawa Quality Assessment Scale (NOS) score for observational studies and JADAD score for randomized controlled trials. Publication bias was evaluated…

OBJECTIVES: Many risk scores have been proposed to predict presence of advanced colorectal neoplasms, but a comprehensive comparison conducted in the same population is sparse. The aim of this study was to evaluate and directly compare the diagnostic performance of published risk prediction models for advanced colorectal neoplasms. METHODS: Data were drawn from 2 cohorts of subjects undergoing screening colonoscopy in Germany, i.e., KolosSal (n = 16,195) and BliTz (n = 7,444). Absolute risks and relative risks were generated for the presence of at least 1 advanced neoplasm, taking the lowest risk group as the reference group. Performance of risk models was assessed by the area under the receiver operating characteristic curve (AUC) and compared by the net reclassification improvement. RESULTS: The 2 cohorts included 1,917 (11.8%) and 848 (11.4%) participants with advanced neoplasm, respectively. Absolute risks were mostly between 5% and 10% among participants in the lowest risk group and between 15% and 20% among participants in the highest risk group, and relative risks mostly…

OBJECTIVES: Celiac disease (CD) may occur in genetically predisposed individuals exposed to gluten, but it is unclear whether the amount of gluten influences the risk of disease. We aimed at determining whether the amount of gluten intake at age 18 months predicted later risk of CD. METHODS: In an observational nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa), we included 67,608 children born during 2000-2009 and followed up for a mean of 11.5 years (range 7.5-15.5) after exclusions for missing data. Information regarding CD diagnosis was obtained from the Norwegian Patient Register 2008-2016 and from parental questionnaires at child age 7 and 8 years. We estimated gluten intake at age 18 months from a prospectively collected parental questionnaire. RESULTS: CD was diagnosed in 738 children (1.1%, 62% girls). The mean estimated amount of gluten in the diet at 18 months was 8.8 g/d (SD 3.6). The adjusted relative risk of CD was 1.10 (95% confidence interval 1.03-1.18) per SD increase in daily gluten amount at age 18 months. Children in the upper quartile of…

INTRODUCTION: Low-grade chronic inflammation has been suggested to play a role in uncomplicated asymptomatic and symptomatic diverticular disease. However, population-based studies are lacking. We investigated whether community participants with diverticulosis, with or without symptoms, would have colonic inflammation on histology and serology. METHODS: In a nested case-control study of 254 participants from the population-based colonoscopy (PopCol) study, colonic histological inflammatory markers and serological C-reactive protein levels were analyzed in cases with diverticulosis and controls without diverticulosis. Statistical methods included logistic and linear regression models. RESULTS: Background variables including age (P = 0.92), sex (P = 1.00), body mass index (P = 0.71), smoking (P = 0.34), and recent antibiotic exposure (P = 0.68) were similar between cases and controls. Cases reported more abdominal pain (P = 0.04) and diarrhea symptoms (mushy and high-frequency stools) than controls (P = 0.01 and P = 0.03, respectively) but were otherwise similar. The median C-reactive…

1Division of Digestive Diseases and Nutrition, Joy McCann Culverhouse Center for Swallowing Disorders, Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida, USA; 2Division of Gastroenterology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, USA. Correspondence: Joel E. Richter, MD, MACG. E-mail: [email protected].

OBJECTIVES: To compare the perceptions of constipation among the general population (with and without constipation), general and specialist doctors, and the Rome IV criteria. METHODS: A cross-sectional survey using a self-administered questionnaire where participants were asked to report symptoms perceived to be most important for a diagnosis of constipation. Participants also judged 10 case studies in which constipation was either present or absent according to Rome IV criteria. RESULTS: Two thousand five hundred fifty-seven members of the general population (934 with self-reported constipation and 1,623 without constipation), 411 general practitioners (GPs) and 365 gastroenterology specialists completed the questionnaire. Of the 934 with self-reported constipation, 877 (94%) met Rome IV criteria for functional constipation, whereas of the 1,623 who did not self-report constipation, 473 (29%) actually met Rome IV criteria. Infrequent bowel movements were perceived as important for diagnosing constipation by less than a third of the constipated general population (26%), compared…

OBJECTIVES: Chronic hepatitis C-infected patients who do not respond to nonstructural 5A inhibitor-containing regimens have few treatment options. It is unclear if patients who fail glecaprevir/pibrentasvir (G/P) (Mavyret) can be re-treated with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) because the latter's registration trials antedated the availability of the former. METHODS: Adherent virologic failures to G/P were re-treated with 12 weeks of SOF/VEL/VOX, and all subjects underwent resistance testing at baseline and again with subsequent relapse. RESULTS: Ninety-four percent of subjects achieved sustained virologic response with re-treatment, despite 90% of 31 subjects harboring nonstructural 5A inhibitor resistance-associated mutations at baseline. DISCUSSION: SOF/VEL/VOX is an effective regimen for virologic failures to G/P.

OBJECTIVES: Hypertension has been linked to the presence and severity of nonalcoholic fatty liver disease (NAFLD) through unclear mechanisms. The gain-of-function rs5186 A1166C variant in angtiotensin receptor type 1 (AGTR1) gene has been linked to hypertension, cardiovascular disease and metabolic syndrome. We assessed the impact of AGTR1 A1166C variant on NAFLD incidence and severity and on glucose and lipid metabolism and explored the underlying mechanisms. METHODS: We followed up 314 healthy nonobese, nondiabetic, nonhypertensive, insulin-sensitive participants in a population-based study, characterized for AGTR1 rs5186 A1166C variant, adipokine profile, inflammatory and endothelial dysfunction markers. An independent cohort of 78 biopsy-proven nondiabetic NAFLD patients and controls underwent an oral glucose tolerance test with Minimal Model analysis of glucose homeostasis, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, MCP-1, calprotectin, and nuclear factor-κB activation in circulating mononuclear cells. RESULTS: AGTR1 A1166C polymorphism…

OBJECTIVES: Diagnosis of covert hepatic encephalopathy (CHE) is challenging and often neglected in clinical practice. The aim of this study was to develop an easy-to-perform score to predict CHE in patients with cirrhosis. METHODS: For the development or validation cohort of the proposed clinical CHE score, 142 or 96 consecutive patients with cirrhosis were prospectively enrolled. The Psychometric Hepatic Encephalopathy Score was used to detect minimal hepatic encephalopathy. All patients were examined with the simplified animal naming test and were asked to complete the Chronic Liver Disease Questionnaire. We followed the TRIPOD guideline for development, validation, and reporting of the proposed score. RESULTS: The clinical covert hepatic encephalopathy score containing the variables-clinically detectable ascites, history of overt hepatic encephalopathy (OHE), albumin serum level, activity subdomain of the Chronic Liver Disease Questionnaire, and simplified animal naming test-discriminated best between patients with and without CHE. We generated 2 cutoff values for the…

INTRODUCTION: Cross-sectional data note lower levels of testosterone and sex hormone-binding globulin (SHBG) levels in men with nonalcoholic fatty liver disease (NAFLD). Whether sex hormone levels in young men are predictive of later risk of NAFLD is not known. METHODS: Among men in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults study (mean age 50; n = 837), we assessed whether testosterone and SHBG levels measured at study year 10 (median age 35 years) were associated with prevalent NAFLD at study year 25. NAFLD was defined using noncontrast abdominal computed tomography (CT) scan after excluding other causes of hepatic steatosis. The association of testosterone and SHBG with prevalent NAFLD was assessed by logistic regression. RESULTS: Total testosterone levels in young men were inversely associated with subsequent prevalent NAFLD on unadjusted analysis (odds ratio [OR] 0.64, 95% confidence interval 0.53-0.7, P < 0.001), although no longer significant after adjustment for year 10 metabolic covariates as well as change in metabolic…