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      Gluten-Free Diet in Celiac Disease—Forever and for All?

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          Abstract

          The gluten-free diet is the only effective treatment available for celiac disease. However, it is difficult to adhere to and a closer look on the diet’s implementation and indications reveals several ambiguities: Not only is there controversy on the threshold of gluten that can be tolerated in the frame of a strict gluten-free diet, but it is also unclear whether the gluten-free diet is an appropriate treatment in patient subgroups with asymptomatic or potential celiac disease. Reports from a number of research groups suggest that a certain proportion of patients may effectively develop tolerance to gluten and thus become suitable for gluten reintroduction over time. In this review, we set out to create an overview about the current state of research as regards the definition of a strict gluten-free diet in terms of the gluten thresholds considered tolerable and the indication for a gluten-free diet in the absence of histological abnormalities or symptoms. Furthermore, we discuss the concept that a gluten-free diet must be followed for life by all patients.

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          Most cited references56

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          Increased prevalence and mortality in undiagnosed celiac disease.

          The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. This study included 9133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 gender-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n = 5558) or age at sampling (n = 7210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Of 9133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio = 3.9; 95% confidence interval, 2.0-7.5; P < .001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts, respectively, than in the Air Force cohort (both P < or = .0001). During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD seems to have increased dramatically in the United States during the past 50 years.
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            Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet.

            Clinical response is typically observed in most adults with celiac disease (CD) after treatment with a gluten-free diet (GFD). The rate of mucosal recovery is less certain. The aims of this study were (1) to estimate the rate of mucosal recovery after GFD in a cohort of adults with CD, and (2) to assess the clinical implications of persistent mucosal damage after GFD. The study group included adults with biopsy-proven CD evaluated at the Mayo Clinic who had duodenal biopsies at diagnosis and at least one follow-up intestinal biopsy to assess mucosal recovery after starting a GFD. The primary outcomes of interest were mucosal recovery and all-cause mortality. Of 381 adults with biopsy-proven CD, 241 (73% women) had both a diagnostic and follow-up biopsy available for re-review. Among these 241, the Kaplan-Meier rate of confirmed mucosal recovery at 2 years following diagnosis was 34% (95% confidence interval (CI): 27-40%), and at 5 years was 66% (95% CI: 58-74%). Most patients (82%) had some clinical response to GFD, but it was not a reliable marker of mucosal recovery (P=0.7). Serological response was associated with confirmed mucosal recovery (P=0.01). Poor compliance to GFD (P<0.01), severe CD defined by diarrhea and weight loss (P<0.001), and total villous atrophy at diagnosis (P<0.001) were strongly associated with persistent mucosal damage. There was a trend toward an association between achievement of mucosal recovery and a reduced rate of all-cause mortality (hazard ratio=0.13, 95% CI: 0.02-1.06, P=0.06), adjusted for gender and age. Mucosal recovery was absent in a substantial portion of adults with CD after treatment with a GFD. There was a borderline significant association between confirmed mucosal recovery (vs. persistent damage) and reduced mortality independent of age and gender. Systematic follow-up with intestinal biopsies may be advisable in patients diagnosed with CD as adults.
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              Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease.

              The relationship between celiac disease and many autoimmune disorders has been explained by the sharing of a common genetic factor. In a multicenter national study, we examined the relationship between the prevalence of autoimmune disorders in celiac disease and the duration of exposure to gluten. Over a 6-month period, 909 patients with celiac disease (group A; mean age, 16.1 +/- 3.8 years; grouped according to age at diagnosis into three subgroups [group A1, 10 years]), 1268 healthy controls (group B; mean age, 20.8 +/- 4.5 years), and 163 patients with Crohn's disease (group C; mean age, 28.8 +/- 10 years) were evaluated for the presence of autoimmune disorders. Prevalence of autoimmune disorders in group A was significantly higher than in group B (14% vs. 2.8%; P < 0.000001) but not higher than in group C (12.9%). Prevalence of autoimmune disorders in celiac disease increased with increasing age at diagnosis: 5.1% in group A1, 17% in group A2, and 23.6% in group A3 (P = 0.000001). In group A3, the prevalence of autoimmune disorders was significantly higher than in group C. In a logistic regression model, age at diagnosis was the only significant predictor variable of the odds of developing an autoimmune disorder (r = 0.3; P < 0.000001). Our data show for the first time that the prevalence of autoimmune disorders in celiac disease is related to the duration of exposure to gluten.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                18 November 2018
                November 2018
                : 10
                : 11
                : 1796
                Affiliations
                [1 ]Division of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, 12203 Berlin, Germany; alice.itzlinger@ 123456charite.de (A.I.); federica.branchi@ 123456charite.de (F.B.)
                [2 ]Center for the Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; luca.elli@ 123456policlinico.mi.it
                Author notes
                [* ]Correspondence: michael.schumann@ 123456charite.de ; Tel.: +49-(0)30-450514536
                Author information
                https://orcid.org/0000-0002-0873-0759
                Article
                nutrients-10-01796
                10.3390/nu10111796
                6267495
                30453686
                69685f75-d9dc-4f57-8374-3bb7b884f23c
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 October 2018
                : 15 November 2018
                Categories
                Review

                Nutrition & Dietetics
                gluten,adherence,serology,villous atrophy,mucosal recovery,threshold
                Nutrition & Dietetics
                gluten, adherence, serology, villous atrophy, mucosal recovery, threshold

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