-
1.
Guidelines for best practices in monitoring established coeliac disease in adult patients.
Elli, L, Leffler, D, Cellier, C, Lebwohl, B, Ciacci, C, Schumann, M, Lundin, KEA, Chetcuti Zammit, S, Sidhu, R, Roncoroni, L, et al
Nature reviews. Gastroenterology & hepatology. 2024;(3):198-215
Abstract
Coeliac disease (CeD) is an immunological disease triggered by the consumption of gluten contained in food in individuals with a genetic predisposition. Diagnosis is based on the presence of small bowel mucosal atrophy and circulating autoantibodies (anti-type 2 transglutaminase antibodies). After diagnosis, patients follow a strict, life-long gluten-free diet. Although the criteria for diagnosis of this disease are well defined, the monitoring phase has been studied less and there is a lack of specific guidelines for this phase. To develop a set of clinical guidelines for CeD monitoring, we followed the Grading of Recommendations Assessment, Development and Evaluation methodology. Statements and recommendations with the level of evidence were developed and approved by the working group, which comprised gastroenterologists, pathologists, dieticians and biostatisticians. The proposed guidelines, endorsed by the North American and European coeliac disease scientific societies, make recommendations for best practices in monitoring patients with CeD based on the available evidence. The evidence level is low for many topics, suggesting that further research in specific aspects of CeD would be valuable. In conclusion, the present guidelines support clinicians in improving CeD treatment and follow-up and highlight novel issues that should be considered in future studies.
-
2.
Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study.
Lebwohl, B, Ma, C, Lagana, SM, Pai, RK, Baker, KA, Zayadi, A, Hogan, M, Bouma, G, Cellier, C, Goldsmith, JD, et al
Gastroenterology. 2024;(1):88-102
Abstract
BACKGROUND & AIMS There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
-
3.
Follow-Up of Celiac Disease in Adults: "When, What, Who, and Where".
Mulder, CJJ, Elli, L, Lebwohl, B, Makharia, GK, Rostami, K, Rubio-Tapia, A, Schumann, M, Tye-Din, J, Zeitz, J, Al-Toma, A
Nutrients. 2023;(9)
Abstract
For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.
-
4.
An Analysis of 5 Years of Randomized Trials in Gastroenterology and Hepatology Reveals 52 Medical Reversals.
Yopes, MC, Mozeika, AM, Liebling, S, Haslam, A, Prasad, V, Lebwohl, B
Digestive diseases and sciences. 2022;(6):2011-2018
Abstract
BACKGROUND AND AIMS One manifestation of low-value medical practice is the medical reversal, a practice in widespread use that, once subjected to a randomized controlled trial (RCT), is found to be no better-or worse-than a prior established standard of care. We aimed to determine the prevalence of medical reversals in gastroenterology (GI) journals and characterize these reversals. METHODS We searched the American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, Gastroenterology, Gut, Hepatology, and the Journal of Hepatology, reviewing studies published in 2015-2019. We identified RCTs that tested an established clinical practice and produced negative results, considered tentative reversals. Any systematic review or meta-analysis that included the article was categorized as confirming the reversal, refuting the reversal, or providing insufficient data. RESULTS During the 5-year period, we identified 5,898 original articles, of which 212 tested an established practice and 52 were categorized as unrefuted medical reversals (25% of articles testing standard of care). Of the reversals, 21 (40%) tested procedures and devices, 15 (29%) tested medications, and 8 (15%) tested vitamins/supplements/diet. Twenty-three (44%) considered the alimentary tract, 12 (23%) considered the liver, pancreas, or biliary tract, and 17 (33%) considered endoscopy. Thirty-eight (73%) were funded exclusively by non-industry sources. CONCLUSION This review reveals a total of 52 reversals across all subfields of GI and medical, procedural, screening, and diagnostic interventions, occurring in 25% of randomized trials testing an established practice. More research is needed to determine the optimal way to engage stakeholders and remove reversed practices from medical care.
-
5.
AGA Clinical Practice Update on the Evaluation and Management of Seronegative Enteropathies: Expert Review.
Leonard, MM, Lebwohl, B, Rubio-Tapia, A, Biagi, F
Gastroenterology. 2021;(1):437-444
Abstract
DESCRIPTION Our aim was to provide a consensus statement for the best approaches for diagnosis and management of patients with suspected enteropathy, but negative results from serologic tests for celiac disease (seronegative enteropathy). METHODS We collected findings from published cohort, case-control, and cross-sectional studies of diagnosis and case series and descriptive studies of management of patients believed to have celiac disease or other enteropathies unrelated to gluten, but negative results from serologic tests. BEST PRACTICE ADVICE 1: Review histologic findings with experienced pathologists who specialize in gastroenterology. BEST PRACTICE ADVICE 2: Serologic tests are essential for an accurate diagnosis of celiac disease. For patients with suspected celiac disease but negative results from serologic tests, total IgA level should be measured; patients should also be tested for anti-tissue transglutaminase, IgA against deamidated gliadin peptide, and endomysial antibody (IgA). Patients with total IgA levels below the lower limit of detection and IgG against tissue transglutaminase or deamidated gliadin peptide, or endomysial antibody, should be considered to have celiac disease with selective IgA deficiency rather than seronegative celiac disease. BEST PRACTICE ADVICE 3: Patients' diets should be carefully reviewed and duodenal biopsies should be collected and analyzed at the time of serologic testing to determine exposure to gluten and accuracy of test results. BEST PRACTICE ADVICE 4: Thorough medication histories should be collected from patients, with attention to angiotensin II receptor blockers, such as olmesartan, along with travel histories to identify potential etiologies of villous atrophy. This will guide additional testing. BEST PRACTICE ADVICE 5: Patients should be analyzed for disease-associated variants in human leukocyte antigen genes; results must be carefully interpreted. Negative results can be used to rule out celiac disease in seronegative patients. BEST PRACTICE ADVICE 6: Patients with suspected celiac disease who are seronegative but have villous atrophy and genetic risk factors for celiac disease must undergo endoscopic evaluation after 1-3 years on a gluten-free diet to evaluate improvements in villous atrophy. A diagnosis of seronegative celiac disease can then be confirmed based on clinical and histologic markers of improvement on the gluten-free diet. BEST PRACTICE ADVICE 7: Seronegative patients with an identified cause for enteropathy should be treated accordingly; a follow-up biopsy might or might not be necessary. BEST PRACTICE ADVICE 8: Patients with persistent signs and symptoms who do not respond to a gluten-free diet, and for whom no etiology of enteropathy is ultimately identified, should be treated with budesonide. CONCLUSIONS These best practice guidelines will aid in diagnosis and management of patients with suspected celiac disease, but negative results from serologic tests.
-
6.
Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review.
Quan, J, Panaccione, N, Jeong, J, Underwood, FE, Coward, S, Windsor, JW, Ronksley, PE, Gidrewicz, D, deBruyn, J, Turner, JM, et al
Journal of pediatric gastroenterology and nutrition. 2021;(5):704-711
Abstract
OBJECTIVE The aim of the study was to perform a systematic review assessing the research investigating the association between celiac disease (CD) and autism spectrum disorder (ASD). METHODS A literature search of MEDLINE and EMBASE was performed without limits placed on year or language. Observational studies reporting on the occurrence of CD among patients with ASD and/or the occurrence of ASD among patients with CD were included. Study design, characteristics, diagnostic criteria for ASD and CD, and the frequency of positive cases in the studied sample were recorded. Study quality was assessed using an adapted Newcastle-Ottawa Quality Assessment Scale. Due to substantial heterogeneity between studies, a meta-analysis was not performed. RESULTS Of the 298 unique citations identified within our search strategy, 17 articles evaluating the association between CD and ASD were included. Of those articles, 13 observed samples of patients with ASD, and 6 observed samples of patients with CD. Overall, most studies had small sample sizes and reported no evidence for an association between the 2 conditions. However, a limited number of population-based studies of higher quality suggested a potential association between CD and ASD. CONCLUSIONS Most studies assessing an association between CD and ASD are at risk for systematic and/or random error. A potential link has, however, been shown in a handful of high-quality studies, and, therefore, this comorbidity cannot be ruled out. Future studies should recruit larger sample sizes, include precise definitions of CD and ASD, and exclude patients with ASD on a gluten-free diet.
-
7.
Prevalence of Clostridioides difficile and Other Gastrointestinal Pathogens in Patients with COVID-19.
Laszkowska, M, Kim, J, Faye, AS, Joelson, AM, Ingram, M, Truong, H, Silver, ER, May, B, Greendyke, WG, Zucker, J, et al
Digestive diseases and sciences. 2021;(12):4398-4405
-
-
Free full text
-
Abstract
BACKGROUND Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. AIMS This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. METHODS We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. RESULTS Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24-0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. CONCLUSIONS Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.
-
8.
Celiac disease: clinical update.
Uche-Anya, E, Lebwohl, B
Current opinion in gastroenterology. 2021;(6):619-624
Abstract
PURPOSE OF REVIEW This review highlights literature from the past year and explores the impact on current understanding of celiac disease pathogenesis, diagnosis, and management. RECENT FINDINGS In contrast to earlier clinical trials, recent data suggests that early gluten introduction may protect against the development of celiac disease. Celiac disease is underdiagnosed, associated with high burden of disease and linked to excess mortality risk, yet, there remains considerable uncertainty regarding the utility of mass screening in asymptomatic individuals. The gut microbiome is increasingly implicated in celiac disease pathogenesis, although the exact mechanism is undefined. Probiotics have been proposed as a disease-modifying option for celiac disease but most studies assessing efficacy are of low-quality. Patients with celiac disease do not appear to be at increased risk of contracting or developing adverse outcomes from COVID-19. Little is known about the pathogenesis of nonceliac gluten sensitivity; however, recent findings suggest an autoimmune basis for the condition. SUMMARY Current understanding of celiac disease continues to advance, though significant knowledge gaps remain. Large, rigorous, prospectively designed studies are needed to further characterize celiac disease pathogenesis, management and therapeutic options.
-
9.
Epidemiology, Presentation, and Diagnosis of Celiac Disease.
Lebwohl, B, Rubio-Tapia, A
Gastroenterology. 2021;(1):63-75
Abstract
The incidence of celiac disease is increasing, partly because of improved recognition of, and testing for, the disease. The rise in incidence is also due to a real increase of this immune-based disorder, independent of disease detection. The reasons for this true rise in recent decades are unknown but may be related to environmental factors that may promote loss of tolerance to dietary gluten. Strategies to reduce the development of celiac disease have not been proven successful in randomized trials, but the quantity of early-life gluten exposure has been a major focus of prevention efforts. The criteria for the diagnosis of celiac disease are changing, but in adults, diagnosis still depends on the presence of duodenal villous atrophy while the patient is on a gluten-containing diet, along with findings from serology analysis. Although guidelines in the United States continue to mandate a biopsy at all ages, some children receive a diagnosis of celiac disease without a biopsy. If proven accurate and scalable, assays that detect gluten-HLA tetramer complexes might be used in diagnosis to be made in the context of a gluten-free diet without intestinal biopsy.
-
10.
Celiac disease serology and gut microbiome following proton pump inhibitor treatment.
Jang, S, Lebwohl, B, Abrams, JA, Green, PHR, Freedberg, DE, Alaedini, A
Medicine. 2020;(35):e21488
-
-
Free full text
-
Abstract
BACKGROUND Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to proton pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome. METHODS We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks. RESULTS The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales. CONCLUSIONS The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.