Optimising the follow-up of adult coeliac disease with a clinical-based score to identify patients in need of a histological reassessment: a retrospective single centre study.

AbstractFollow-up modalities for adult coeliac patients remain controversial. Non-invasive markers to identify coeliac patients on a gluten-free diet (GFD) with persistence of villous atrophy (VA) are still lacking. We aim to develop a score to stratify coeliac patients on a GFD according to their risk of having persistent VA and to tailor follow-up modalities accordingly. The clinical notes of over 700 coeliac patients attending our unit (September 1999–November 2018) were retrospectively examined. A total of 273 patients on a GFD with a histological follow-up performed 12–24 months after diagnosis were selected. We developed a bivariable model based on diet adherence and clinical response evaluated by previously validated methods. A four-level score (0·5, 1·5, 3, 4) was obtained. Patients on a strict GFD and with good clinical conditions (score 4) have a very low risk of persistence of VA (2 (95 % CI 1, 5) %). Conversely, the risk is very high (46 (95 % CI 25, 68) %) in patients with poor adherence to a GFD and unsatisfactory clinical response (score 0·5). A score of 1·5 (poor GFD adherence and persistent well-being) is linked with a high risk (23 (95 % CI 14, 36) %). Risk is intermediate (6 (95 % CI 3, 10) %) in patients scoring 3 (strict GFD and no/partial clinical improvement). Three patients who developed complications belonged to this scenario. Patients at low risk of persistent VA can be followed-up non-invasively, whereas a biopsy should be repeated in those at high/very high risk. Case-by-case evaluation is needed in patients at intermediate risk. Studies on a larger sample size are required to confirm these data

STUDY OF THE CLINICAL AND MOLECULAR PHENOTYPE AND NATURAL HISTORY OF ENTEROPATHIES WITH VILLOUS ATROPHY OF UNKNOWN ORIGIN AND THERAPEUTIC POTENTIAL OF BONE MARROW DERIVED MESENCHYMAL STEM CELLS

This PhD project started in 2016 and aimed firstly to define the clinical and molecular phenotype and natural history of enteropathies with villous atrophy of undefined etiology, that need to be clearly distinguished from both coeliac disease, its complications and other non-coeliac enteropathies with villous atrophy due to a known cause. Secondly, we aimed to evaluate the therapeutic potential of mesenchymal stem cell infusions for the treatment of these rare conditions. The main clinical part of this PhD project (February 2018-August 2019) has been carried out in collaboration with the NHS England National Centre for coeliac disease and rare diseases, Sheffield, UK. The results outlined in the thesis show that non-coeliac enteropathies are extremely heterogeneous conditions characterised by different prognoses. More specifically, we have described the largest cohort of patients affected by enteropathies with villous atrophy of unknown origin and we have shown for the first time that they consist of three groups with distinct clinical phenotype and natural history. Mortality in these enteropathies of undefined origin is mainly due to the development of lymphoproliferative complications. Hypoalbuminaemia and age at diagnosis may be useful predictors to identify patients at greatest risk of poor prognosis, therefore needing more aggressive and targeted therapies, such as mesenchymal stem cells

Seronegative coeliac disease: clearing the diagnostic dilemma

Seronegative coeliac disease is a poorly defined form of coeliac disease that poses an important challenge to clinicians particularly with regards to the differential diagnosis. This is probably because of lack of a consensus on its definition and incorrect use of specific coeliac serology. Seronegative coeliac disease (SCD) is uncommon and epidemiological data are scarce and contrasting. Therefore, the aim of this review is to provide a critical summary of the most recent work on this topic and a definition of SCD

Study of the microbiota composition in adult celiac disease

Celiac Disease (CD) is an autoimmune, inflammatory disorder of the small intestine that involves a complex interplay between genetic and environmental factors. Gluten is the key, but not the unique, environmental trigger of CD in genetically predisposed individuals. To explore the existence of additional environmental factors with a role in pathogenesis and clinical picture a role for imbalances (“dysbiosis”) in the gut microbiota is the focus of our ongoing project, funded by “Associazione Italiana Celiachia” (AIC), specifically addresses these poorly understood aspect. The general aims of our project are to obtain a comparative metagenomic picture of the salivary, duodenal and fecal microbiota composition in four categories of adult CD patients (10 potential, 10 refractory, 20 active neo-diagnosed, 20 treated patients under gluten-free diet) vs. non-CD controls (n=20, suffering of functional dyspepsia). This allows to address the following questions: (i) does the eventual dysbiosis anticipates or follows the development of enteropathy?; (ii) does the gluten-free diet restore a normal composition of the microbiota?; (iii) is there any difference between active and complicated conditions, i.e.: are micobiota changes larger in complicated patients? In our poster, we will present some of these preliminary findings

Is it time to rethink the burden of non-coeliac gluten sensitivity? A systematic review

Non-coeliac gluten sensitivity (NCGS) is still a poorly defined clinical condition. This review aims to describe the clinical features of subjects with a symptomatic response to gluten intake, and to estimate the prevalence of NCGS