Federica Branchi

Evidence for the presence of non-celiac gluten sensitivity in patients with functional gastrointestinal symptoms: Results from a multicenter randomized double-blind placebo-controlled gluten challenge

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

Cereal crops and cereal consumption have had a vital role in Mankinds history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patients clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.

The role of ultrasound elasticity imaging in predicting ileal fibrosis in Crohn's disease patients

Backgound:Bowel wall fibrosis is associated with a complicated disease behavior in patients with Crohns disease (CD). The quantitative assessment of fibrosis severity in CD-affected bowel can help clinical decision making. Our aim was to evaluate the feasibility, reliability, and reproducibility of ultrasound elasticity imaging (UEI) toward the assessment of ileal fibrosis in CD patients. Methods:Twenty-three consecutive patients with ileal or ileocolonic CD, elected for surgical resection of the terminal ileum, underwent bowel ultrasound and UEI. Twenty inflammatory CD patients without complications were enrolled as controls. Bowel wall stiffness was evaluated with UEI by means of color scale and quantitative strain ratio measurement. The severity of bowel wall fibrosis and inflammation were evaluated on histological sections by semiquantitative and quantitative image analysis and used as a reference standard. Results:The UEI strain ratio measurement was significantly correlated with the severity of bowel fibrosis at both semiquantitative and quantitative histological image analysis: it was characterized by an excellent discriminatory ability for severe bowel fibrosis (area under the receiver operating characteristic curve: 0.917; 95% confidence interval, 0.788–1.000). UEI strain ratio measurements were characterized by an excellent interrater agreement. At multivariate analysis, bowel wall fibrosis proved the only independent determinant of the strain ratio. The ileal strain ratio of inflammatory CD patients was significantly lower than in operated CD patients with severe fibrosis. Conclusions:UEI can be used to assess ileal fibrosis in CD patients.

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role, clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus (HBV) infection. During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations, mainly: invasiveness, costs, low reproducibility, poor acceptance by patients. Elastographic techniques conceived to assess liver stiffness, in particular transient elastography, and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis. Recent evidence highlights that both liver stiffness and some bio-chemical markers correlate with survival and major clinical end-points such as liver decompensation, development of hepatocellular carcinoma and portal hypertension. Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis. Given their prognostic value, transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes. Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

A study evaluating the bidirectional relationship between inflammatory bowel disease and self-reported non-celiac gluten sensitivity.

Background:Non-celiac gluten sensitivity and the associated use of a gluten-free diet (GFD) are perceived to belong to the spectrum of irritable bowel syndrome (IBS). However, recent reports suggest substantial use of a GFD in inflammatory bowel disease (IBD). We assessed the bidirectional relationship between IBD and self-reported non-celiac gluten sensitivity (SR-NCGS). Methods:A cross-sectional questionnaire screened for SR-NCGS and the use of a GFD in 4 groups: ulcerative colitis (n = 75), Crohns disease (n = 70), IBS (n = 59), and dyspeptic controls (n = 109). We also assessed diagnostic outcomes for IBD in 200 patients presenting with SR-NCGS. Results:The prevalence of SR-NCGS was 42.4% (n = 25/59) for IBS, followed by 27.6% (n = 40/145) for IBD, and least among dyspeptic controls at 17.4% (n = 19/109); P = 0.015. The current use of a GFD was 11.9% (n = 7/59) for IBS, 6.2% (n = 9/145) for IBD, and 0.9% (1/109) for dyspeptic controls; P = 0.02. No differences were established between ulcerative colitis and Crohns disease. However, Crohns disease patients with SR-NCGS were significantly more likely to have stricturing disease (40.9% versus 18.9%, P = 0.046), and higher mean Crohns Disease Activity Index score (228.1 versus 133.3, P = 0.002), than those without SR-NCGS. Analysis of 200 cases presenting with SR-NCGS suggested that 98.5% (n = 197) could be dietary-related IBS. However, 1.5% (n = 3) were found to have IBD; such patients had associated alarm symptoms, and/or abnormal blood parameters, prompting colonic investigations. Conclusions:SR-NCGS is not only exclusive to IBS but also associated with IBD, where its presence may be reflecting severe or stricturing disease. Randomized studies are required to further delineate the nature of this relationship and clarify whether a GFD is a valuable dietetic intervention in selected IBD patients.

The role of transient elastography in patients with hepatitis B viral disease

This review focuses on the role of ultrasound and transient elastography (TE) in patients with hepatitis B virus (HBV) infection. Among the ultrasonographic signs analyzed, liver surface nodularity has the highest diagnostic accuracy and is particularly useful in confirming the presence of severe fibrosis or cirrhosis, due to its high specificity. The role of TE in patients with hepatitis B virus disease was assessed in inactive carriers and patients with chronic liver disease (CHB). In inactive HBV carriers, mean TE values are similar to normal controls and significantly lower than in patients with CHB. In this latter group, the available studies showed a significant positive correlation between TE values and fibrosis stages at liver histology. However, as for HCV patients, there is a certain degree of overlap among the lower stages of hepatic fibrosis and the accuracy of this technique is not optimal for the diagnosis of significant fibrosis, whereas its diagnostic performances are higher for the diagnosis of liver cirrhosis. The development of diagnostic algorithms, with a confirmatory and an exclusion liver stiffness threshold, seems to be a promising tool for a correct classification of patients.

Hepatic Hemangioma in Celiac Patients: Data from a Large Consecutive Series

Background and Aims. Hepatic hemangioma (HH) has a widely ranging prevalence. The etiology is unclear; however, associations with autoimmune disorders have been described. We aimed at evaluating the prevalence of HH in celiac disease. Methods. Ninety-seven consecutive patients with celiac disease (18 M, 79 F, median age 41, and range 17–84 years) underwent liver ultrasound between January 2011 and 2012. The findings were compared with those of 1352 nonceliac patients (581 M, 771 F, median age 50, and range 16–94 years), without liver disease or previously detected HH, who underwent US in the same period. Results. Ultrasonographic findings consistent with HH were observed in 14 celiac patients (14.4%), a prevalence significantly higher than in controls (69 cases, 5.1%) (P = 0.0006). Subgroup analysis showed that, among women, the prevalence of HH was 16.4% in the celiac disease group (13/79) compared with 5.9% in controls (46/771) (P = 0.002). In celiac setting, HH had a median diameter of 1.3 cm and presented as a single lesion in 12 cases (86%). Conclusions. Our findings are consistent with a significantly higher prevalence of HH in celiac patients. Although mechanisms underlying this association remain unclear, autoimmune and metabolic processes, as well as alterations of gut-liver axis equilibrium, could play a role.

Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy

Background Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. Materials and methods This was a retrospective, multicentre study (2010–2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. Results Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn’s disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3–11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92–0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. Conclusion In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.

Celiac Disease and Drug-Based Therapies: Inquiry into Patients Demands

Background/Aim: Medical research is looking for alternative drug-based options to the gluten-free diet (GFD) for celiac disease. We aimed at evaluating the need for alternative therapies perceived by celiac patients. Methods: During the 2013 meeting of the Lombardy section of the Italian Celiac Patients Association, adult subjects were invited to fill in a questionnaire investigating their clinical profile in relation to compliance to the diet, quality of life (QOL) as well as their opinion on alternative therapies. Results: Three hundred and seventy two patients (76 m, mean age 41.7 ± 13.9 years) completed the questionnaire. Patients reported a significant improvement in health status (HS) and QOL after the diet was started (p < 0.001). The GFD was accepted by 88% patients, but the need for alternative therapies was reported by 65%. Subjects expressing the need for a drug-based therapy showed a lower increase in QOL (p = 0.003) and HS (p = 0.005) on GFD. The preferred option for an alternative therapy was the use of enzymes (145 subjects), followed by a vaccine (111 subjects). Conclusion: The GFD is favorably accepted by most celiac patients. Nevertheless, a proportion of patients pronounce themselves in favor of the development of alternative drugs.

Ultrasound Elasticity Imaging Predicts Therapeutic Outcomes of Patients With Crohn’s Disease Treated With Anti-Tumour Necrosis Factor Antibodies

Background and Aims Ultrasound elasticity imaging is a non-invasive technique developed to evaluate fibrosis. Measuring tissue strain by ultrasound elasticity imaging can reliably detect severe ileal fibrosis in patients with Crohns disease [CD]. We have hypothesised that a more severe range of fibrosis might influence the therapeutic response to anti-tumour necrosis factor [TNF] treatment. The aim of this study was to assess the ability of ultrasound elasticity imaging to predict the therapeutic outcome for CD patients. Methods Consecutive patients with ileal/ileocolonic CD, starting anti-TNF treatment, were enrolled for the study. These patients underwent bowel ultrasound and ultrasound elasticity imaging at baseline and at 14 and 52 weeks after anti-TNF treatment. Bowel wall stiffness was quantified by calculating the strain ratio between the mesenteric tissue and the bowel wall. Strain ratio ≥ 2 was used to identify severe ileal fibrosis. Transmural healing at 14 and 52 weeks was defined as bowel wall thickness ≤ 3 mm. Results Thirty patients with CD were enrolled. Five patients underwent surgery for bowel obstruction. The frequency of surgeries was significantly greater in patients with a strain ratio ≥ 2 at baseline [p = 0.003]. A significant reduction of the bowel thickness was observed after 14 and 52 weeks of anti-TNF treatment [p < 0.005]. A significant inverse correlation was observed between the strain ratio values at baseline and the thickness variations following anti-TNF therapy [p = 0.007]; 27% of patients achieved transmural healing at 14 weeks. The baseline strain ratio was significantly lower in patients with transmural healing [p < 0.05]. Conclusions This study shows that ultrasound elasticity imaging predicts therapeutic outcomes for CD patients treated with anti-TNF.