Kumar Pallav

Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease

Objective Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten-free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed. Design 20 adults with biopsy-proven coeliac disease participated. The study included two run-in visits followed by a 14-day GC at a randomly assigned dose of 3 or 7.5 g of gluten/day. Study visits occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured by two pathologists. Antibodies to tissue transglutaminase and deamidated gliadin peptides, lactulose to mannitol ratio (LAMA) and symptoms were assessed at each visit. Results Significant reduction in Vh:Cd (2.2–1.1, p<0.001) and increase in IELs (32.6–51.8, p<0.001) were seen from baseline to day 14. Antibody titres increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses. Conclusions 14 day GC at ≥3 g of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a 2-week GC. Clinical Trials Registration Number http://clinicaltrials.gov # NCT00931892.

Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet.

Coeliac disease is increasingly diagnosed and weight changes are common after adoption of a gluten‐free diet (GFD), however data on body mass index (BMI) changes are limited.

Celiac Disease or Non-Celiac Gluten Sensitivity? An Approach to Clinical Differential Diagnosis

OBJECTIVES:Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging.METHODS:We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing.RESULTS:Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (P<0.0001). In addition, CD subjects were significantly more likely to have a family history of CD (P=0.004), personal history of autoimmune diseases (P=0.002), or nutrient deficiencies (P<0.0001). The positive likelihood ratio for diagnosis of CD of a >2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5–918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5–16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9.CONCLUSIONS:On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.

Noncoeliac enteropathy: the differential diagnosis of villous atrophy in contemporary clinical practice

Background  Duodenal villous atrophy (DVA) is a key diagnostic finding in coeliac disease (CD). However, the differential diagnosis for this finding is broad.

An alerting system improves adherence to follow-up recommendations from colonoscopy examinations.

BACKGROUND & AIMS Systems are available to ensure that results of tests are communicated to patients. However, lack of adherence to recommended follow-up evaluation increases risk for adverse health outcomes and medical or legal issues. We tested the effectiveness of a novel follow-up system for patients due for surveillance colonoscopy examinations. METHODS Electronic medical records from colonoscopies performed 5 years prior were reviewed to identify individuals due for a repeat surveillance colonoscopy examination. Patients were assigned to groups that received the standard of care or a newly developed follow-up system that included a letter to the primary care provider, 2 letters to the patient, and a telephone call to patients who had not yet scheduled an examination by the procedure due date. The primary end point was the percentage of patients who scheduled or completed the colonoscopy examination within 6 months of the due date. Secondary end points included detection rate for adenomas, sex- and ethnicity-specific follow-up rates, and patient satisfaction. RESULTS Of 2609 patient records reviewed, 830 (31.8%) were found to be due for a surveillance colonoscopy examination in the study period. At the conclusion of the study, 241 (44.7%) patients in the intervention arm had procedures scheduled or completed, compared with 66 (22.6%) in the control group (P < .0001). The follow-up system appeared particularly effective among non-white patients; patients reported general satisfaction with the reminder program. CONCLUSIONS A simple protocol of letters and a telephone call to patients who are due for colonoscopy examinations significantly improved adherence to endoscopic follow-up recommendations. This work provides justification for the creation of reminder systems to improve patient adherence to medical recommendations.

Patients With Celiac Disease Have a Lower Prevalence of Non–Insulin-Dependent Diabetes Mellitus and Metabolic Syndrome

BACKGROUND & AIMS We investigated whether risk for non-insulin-dependent diabetes mellitus (NIDDM) and metabolic syndrome are affected by celiac disease. We examined the prevalence of NIDDM and metabolic syndrome among adults with celiac disease, compared with matched controls. METHODS We assessed medical records of 840 patients with biopsy-proven celiac disease for diagnoses of NIDDM, hypertension, or hyperlipidemia; body mass index (BMI); lipid profile; and levels of glucose or glycosylated hemoglobin, to identify those with metabolic syndrome. Patients without celiac disease were matched for age, sex, and ethnicity (n = 840 controls). The prevalence of NIDDM and metabolic syndrome in the celiac disease cohort was compared with that of the controls and subjects included in the National Health and Nutrition Examination Survey. RESULTS Twenty-six patients with celiac disease (3.1%) had NIDDM compared with 81 controls (9.6%) (P < .0001). Similarly, the prevalence of metabolic syndrome was significantly lower among patients with celiac disease than controls (3.5% vs 12.7%; P < .0001). The mean BMI of patients with celiac disease was significantly lower than that of controls (24.7 vs 27.5; P < .0001). However, celiac disease was still associated with a lower risk of NIDDM, after controlling for BMI. CONCLUSIONS The prevalence of NIDDM and metabolic syndrome are lower among patients with celiac disease than in matched controls and the general population. These differences are not explained by differences in BMI. Studies are needed to determine the mechanisms by which celiac disease affects the risk for NIDDM and metabolic syndrome.

Effects of polysaccharopeptide from Trametes versicolor and amoxicillin on the gut microbiome of healthy volunteers: a randomized clinical trial.

Background Interactions between the microbial flora of the intestine and the human host play a critical role in maintaining intestinal health and in the pathophysiology of a wide variety of disorders such as antibiotic associated diarrhea, Clostridium difficile infection, and inflammatory bowel disease. Prebiotics can confer health benefits by beneficial effects on the intestinal microbiome, whereas antibiotics can disrupt the microbiome leading to diarrhea and other side effects. Aim To compare the effects of the prebiotic, polysaccharopeptide from Trametes versicolor, to those of the antibiotic, amoxicillin, on the human gut microbiome Methods Twenty-four healthy volunteers were randomized to receive PSP, amoxicillin, or no treatment (control). Stool specimens were analyzed using bTEFAP microbial ecology methods on seven occasions over 8 weeks from each participant in the active treatment groups and on three occasions for the controls. Results Twenty-two of 24 participants completed the protocol. PSP led to clear and consistent microbiome changes consistent with its activity as a prebiotic. Despite the diversity of the human microbiome we noted strong microbiome clustering among subjects. Baseline microbiomes tended to remain stable and to overshadow the treatment effects. Amoxicillin treatment caused substantial microbiome changes most notably an increase in Escherichia/Shigella. Antibiotic associated changes persisted to the end of the study, 42 days after antibiotic therapy ended. Conclusions The microbiomes of healthy individuals show substantial diversity but remain stable over time. The antibiotic amoxicillin alters the microbiome and recovery from this disruption can take several weeks. PSP from T. versicolor acts as a prebiotic to modulate human intestinal microbiome composition.

Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers

ABSTRACT Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis. This study aimed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 (SB), the antibiotic Amoxicillin-Clavulanate (AC) and the combination on the microbiota and symptoms of healthy humans. Healthy subjects were randomized to one of 4 study groups: SB for 14 days, AC for 7 days, SB plus AC, Control (no treatment). Participants gave stool samples and completed gastro-intestinal symptom questionnaires. Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing (bTEFAP). Only one subject withdrew prematurely due to adverse events. Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone. Control subjects had a stable microbiota throughout the study period. Significant microbiota changes were noted in the AC alone group during antibiotic treatment. AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia, Parabacteroides, and Enterobacter. Microbiota alterations reverted toward baseline, but were not yet completely restored 2 weeks after antibiotherapy. No significant shifts in bacterial genera were noted in the SB alone group. Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores. Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera. S. boulardii treatment can mitigate some antibiotic-induced microbiota changes (dysbiosis) and can also reduce antibiotic-associated diarrhea.

Open conformation tissue transglutaminase testing for celiac dietary assessment

OBJECTIVES Anti tissue-transglutaminase antibody is the mainstay of celiac disease serologic testing. Whilst it has high sensitivity in patients on an unrestricted diet, sensitivity is poor for evaluation of gluten free diet adherence. AIM To assess the utility of a novel assay measuring Immunoglobulin-A antibodies to catalytically active open conformation tissue-transglutaminase in assessment of ongoing gluten exposure in celiac disease patients on an alleged gluten free diet. METHODS Through prospective assessment, 147 patients with celiac disease were divided into good and poor adherence. Open and closed (conventional) tissue-transglutaminase titres were measured using standard enzyme linked immunosorbent assay. 50 patients with inflammatory bowel disease served as disease controls. RESULTS Overall 128 patients had been on gluten free diet for more than six months and 19 were found to be poorly adherent on dietary review. Within this group 13 (68.4%) and 10 (52.6%) patients respectively were positive for the open conformation and conventional assay (p=0.51). Two and one control patients tested positive for closed and open assays respectively. CONCLUSIONS Compared to native assays open conformation tissue-transglutaminase may have higher sensitivity in the poor gluten free diet adherence group and higher specificity in the control population. Larger population studies are warranted to assess whether the open conformation tissue-transglutaminase assay may be superior to the conventional assay.

Immunoglobulin A deficiency in celiac disease in the United States

Multiple European studies report increased prevalence of selective immunoglobulin A deficiency (SIgAD) and partial immunoglobulin A deficiency (PIgAD) in patients with celiac disease (CD). However; prospective data representing North American adults are lacking. While SIgAD precludes the use of IgA‐tissue‐transglutaminase antibody (IgA‐tTG), the effect of PIgAD on IgA‐tTG sensitivity is not well documented. We aim to determine the prevalence and impact of IgA deficiency on CD presentation and diagnosis in North American adult patients.