Introduction

Very few studies have addressed the effect of digestive supplements on gluten hydrolysis, particularly in a complex food matrix.

Aims & Methods

Here, we investigated the effect of such supplements on gluten immunogenic peptides digestion in a standardized pizza.
Pizza samples were digested using the harmonized INFOGEST in vitro digestion method, in absence (CTR) or in the presence of 3 different commercial supplements (i.e., S1, S2 and S3). Gluten content after gastric (G, T120min) or gastro-duodenal (GD, T240min) digestion, was evaluated by RIDASCREEN® Gliadin competitive R5-ELISA and immunogenicity of resistant, deamidated peptides, was assayed on celiac disease derived intestinal-T cell lines (iTCLs).

Results

Supplemental enzymes reduced the R5-specific peptide amount, both at the end of G stage (decrease vs CTR_G: S1 76%, S2 96.5%, S3 98.5%) and after GD digestion (decrease vs CTR_GD: S1 52%, S2 52%, S3 85%). iTCLs activation assays showed a consistent IFN-g reduction by S3-treatment, both for G (55 % decrease vs CTR_G, p=0.027) and GD peptides (93 % decrease vs CTR_GD, p=0.016). Regarding S1, a significant reduction was obtained only at the end of GD digestion (87 % decrease vs CTR_GD, p=0.024) while for S2 reduction did not reach statistical significance (25% decrease vs CTR_G, 69% decrease vs CTR_GD).

Conclusion

In a complex food matrix, different rates of gluten degradation were seen depending on enzyme supplements composition. The highest protease activity was observed for S3. Notably, the R5-ELISA results were not consistent with iTCLs activation assays, suggesting that iTCLs are mandatory to exclude significant residual immunoreactivity of digested products.

Disclosure

This study was supported by an unrestricted grant from Takeda Pharmaceuticals

Introduction

According to the ROME IV criteria, functional dyspepsia (FD) can be subdivided into PDS (postprandial distress syndrome) with meal-related symptoms such as early satiation and postprandial fullness and EPS (epigastric pain syndrome) with meal-unrelated complaints such as epigastric pain or burning. Nausea can also co-exist in FD but the literature is poor in reporting whether this symptom is mainly triggered by meal ingestion. A recent global epidemiology study of gastroparesis-like symptoms showed that the prevalence of nausea or vomiting, in combination with postprandial fullness or early satiation varies between continents.¹

Aims & Methods

This study aims to compare the difference in prevalence rates of nausea within each FD subgroup between western and eastern secondary and tertiary care centers. Adult patients with disorders of gut-brain interaction (DGBI) recruited in 9 western and 7 eastern secondary and tertiary care facilities between the ages of 18 and 70 years completed the Enhanced Asian Rome IV questionnaire (Asian European Gastrointestinal Symptoms cohort or AEGIS). The western centers were located in Belgium, Bulgaria, France, Israel, Italy (2x), Slovakia, Sweden and The United Kingdom while the eastern centers were located in Australia, China, Iran, Japan, Malaysia and Singapore (2x). FD patients were divided into PDS, EPS and PDS-EPS overlap (OVP) subgroups. Patients were furthermore classified as having nausea when this symptom was reported at least once per week. The questionnaire EARQ4 questionnaire was also used to address the relationship between nausea and food intake. Patients were asked how often they experienced nausea, whether nausea was triggered or worsened by meal intake, how often nausea occurred after a meal and if so, how soon after a meal nausea started. A comparison of the prevalence of nausea and meal-related nausea was made between eastern and western patients and among FD subgroups. Continuous variables are reported as median (IQR) and compared with a Kruskal-Wallis test. Categorical variables were compared using a Pearson Chi-square test.

Results

Of the 1074 DGBI patients that completed the survey, 483 were classified as having FD (59.4% PDS, 27.5% EPS, 13.0% PDS-EPS overlap). FD patients from eastern (N=202) and western sites (N=281) had a similar body mass index (22.5 (19.6-25.7) vs. 21.3 (19.7-25.4)kg/m²) and age (39.0 (29.0-55.0) vs. 38.0 (26.0-54.0) years). Eastern sites included significantly more female patients than western sites (43 % vs. 17.5%, p<0.001). PDS and EPS patients from eastern sites had significantly less nausea than PDS and EPS patients from western sites (17.9% vs. 46.3% and 6.8% vs. vs 40.5% respectively, both p<0.001). The majority of FD patients with nausea experienced meal-related nausea with no difference between eastern and western sites (63.9% vs. 73.7%). In PDS patients with nausea, nausea was significantly more triggered or worsened by a meal (72.4%) than in PDS-EPS overlap and EPS (48.6% and 35.3% respectively; p<0.001). All groups reported that meal-related nausea started mostly (> 85%) within 60 minutes after the meal.

Conclusion

In contrast to previous literature, we found that western PDS and EPS patients report nausea more frequently than eastern PDS and EPS patients. In both eastern and western patients nausea was mostly meal-related. Meal-related nausea is more common in PDS than in PDS-EPS overlap and EPS patients. Further research is needed to investigate the role of ethnic factors in the pathophysiology of nausea in functional dyspepsia.

References

Huang IH, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United Eur Gastroenterol J. 2022;10(8):888-897.

Disclosure

Bert Broeders received lecture fees from the Rome Foundation.

Introduction

The severity of bleeding and the time-to-endoscopy are generally recognised as risk factors for mortality in patients with GI bleeding. However, how to grade the bleeding severity (BS) is not clearly defined and it is not clear its relationship with the time-to-endoscopy. We found that the bleeding severity correlates with 5 clinical items: altered mental status, systolic blood pressure ≤100 mmHg, blood ureic nitrogen ≥130 mg/dl, haemoglobin ≤8 gr/dl and clinical presentation with hematemesis.

Aims & Methods

The aim of the study is to evaluate if the interaction between bleeding severity and timing-to-endoscopy could impact on the death risk. A prospective multicentre cohort study, including all consecutive patients with upper gastrointestinal bleeding admitted to 50 Italian hospitals was conducted. Charlson's comorbidity index and ASA scores were used to define the patients’ performance status. According to the previously cited clinical items, we defined bleeding severity (BS) and graded it in low, intermediate, and high-risk classes depending on the presence and the number of items at the time of admission. Timing to endoscopy was defined according to ESGE* guidelines and was divided into 4 time-frames (<6h; 6/12h; 12/24h; >24h).

Results

2,525 patients were included (mean age 68 [±15.8], male 67.3%); the bleeding was non-variceal in 82.3%. Overall, 176 patients died (6.9%); 28 (1.9%) in the low BS group (1,463 patients), 28 (8.6%) in the intermediate BS group (606 pts) and 96 (21%) in the high BS group (p<0.000). In our population, the 4-time frames do not impact on the mortality in the low and intermediate classes of risk. In the high BS class, there is an interaction between the time to endoscopy and the mortality, with the lower mortality observed in the 6/12 hrs frame.

Conclusion

In our population, the death risk gradually rises as the bleeding severity increases. Bleeding severity identifies 3 different classes of death risk and the time to endoscopy seems unrelated to mortality in low and intermediate BS classes. In the high BS patients, the lower mortality was observed in the timing to endoscopy 6-12 hrs.

References

* Ian M. Gralnek et al. Endoscopy 2021; 53: 300–332

Disclosure

nothing to disclose

Introduction

Patients with Hypermobile Ehlers Danlos Syndrome (hEDS) have a high prevalence of Disorders of Gut-Brain Interaction (DGBI) and pose complex nutritional challenges in gastroenterology clinic. Despite this, little is known regarding nutrient intake and adequacy in hEDS.

Aims & Methods

Our aim was to assess nutrient intake and adequacy of patients with hEDS, as well as to determine which factors, including co-existent DGBI, are associated with poor intake. We conducted a cross sectional survey of patients with hEDS from two tertiary neurogastroenterology clinics as well as the Ehlers-Danlos Support UK. Inclusion criteria were adults with hEDS, exclusion criteria were those currently or previously using artificial nutrition. Patients completed the validated semi-quantitative Scottish Collaboration Group Food Frequency Questionnaire (FFQ) alongside questionnaires characterising: demographics, DGBIs (Rome IV), gastrointestinal, mood, somatic and autonomic symptoms, past history of eating disorders and screen for Avoidant Restrictive Food Intake Disorder (ARFID) using the Nine Item Avoidant-Restrictive Scale (NIAS). Nutrient intake was calculated from the FFQ and nutrient adequacy was calculated by comparison with UK daily reference values (DRVs) for age and sex. Unpaired t-tests were performed to compare nutrient intakes among patients with and without comorbidities, including the most common DGBIs.

Results

425 participants were included in the final analysis (mean: 41 years, 96% female). Only 48.5% reported BMI in the normal range, whereas 5.2% were underweight (BMI <18.5 kg/m²)and46.4% were overweight/obese (BMI >25 kg/m²). Only one third met their estimated average requirements (EAR) for energy (kcal/d). The majority met their reference nutrient intake (RNI) for protein (87.3%) and fat (72.5%), in contrast to only 21.2% for carbohydrate. Fibre intakes were very low (AOAC mean 23.7g/day (SD: 12.7) with only 24.7% meeting the RNI of 30 g/d. More than 58% of participants met/exceeded their DRV for micronutrients (zinc, magnesium, copper, manganese and selenium) and >95% for vitamins. Patients with functional nausea (n=157) were less likely to meet their protein requirements compared to those without (82.2% vs. 90.3%, p=0.015) and also had lower intakes for sodium (p=0.02), magnesium (p=0.02), calcium (p=0.01), zinc (p=0.002), selenium (p=0.03), folic acid (p=0.02) and vitamin C (p=0.05). Patients with previous eating disorders were less likely to meet nutrient requirements for thiamine (p=0.01) and vitamin B12 (p=0.04). Patients with ARFID (n=110) were less likely to meet requirements for all nutrients (except fat, calcium, vitamin D, vitamin B12) compared to patients without.

Conclusion

Patients with hEDS are rarely underweight and tend to consume high protein, high fat diets that are low in fibre. Functional nausea is the single most important DGBI impacting nutrient intake, as well as previous eating disorders and disordered eating (ARFID). These factors should be considered by clinicians and dietitians when assessing nutrient intake in this complex patient group.

Disclosure

RT, AF and QA have received a grant from EDS-UK to conduct this study. AF undergoes consulting work for Abbvie.
KW has received research funding from Almond Board of California, Danone, International Nut & Dried Fruit Council, and has a patent for volatile organic compounds in the detection and management of IBS.
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.

Clinical Case Summary

We report a male in his 20s with extensive, treatment resistant Crohn’s disease (CD) presented to Emergency Department with vomiting and increased stool frequency with ascites on examination. Biochemically, he had raised inflammatory markers, elevated liver transaminases, and prolonged prothrombin time. In addition, stool cultures and a full non-invasive liver screen were negative but his faecal calprotectin was raised. He was treated as flare of Crohn’s Disease.
Computed tomography of abdomen was unremarkable. Ascites, splenomegaly, and pneumobilia were discovered by further abdominal ultrasonography. Subsequently, magnetic resonance cholangiopancreatography showed caudate lobe hypertrophy suspicious of Budd-Chiari Syndrome (BCS). This is then confirmed with ultrasound Doppler of hepatic vein demonstrating multiple occluded hepatic veins. Given his negative thrombophilia screen, the vascular thrombosis favours a complication secondary to Crohn’s Disease. He underwent an uncomplicated transjugular intrahepatic portosystemic shunt and started on life-long anticoagulation.
Despite the well-established link between inflammatory bowel disease (IBD) and increased venous thromboembolism (VTE) risk, clot formation in the hepatic vein in BCS is extremely rare.^1,2 BCS has an incidence of 1/100000.²The underlying mechanism of VTE in the flare of IBD is related to the complex interaction between inflammatory mediators and coagulation cascade.¹ Extensive disease, hospitalisation, and chronic steroid use also further heightened the thrombotic state in this case.¹
Our case reiterates the increased VTE risk in IBD patients and highlights a less common association between CD and BCS as compared to ulcerative colitis. Timely diagnosis is key to preventing disease progression to liver failure. As such, BCS should be considered in patients with transaminitis, ascites and splenomegaly during a CD flare.

References

1. Zhang H, Wang X. Risk factors of venous thromboembolism in inflammatory bowel disease: A systematic review and meta-analysis. Frontiers in Medicine. 2021 Jun 28;8. doi:10.3389/fmed.2021.693927
2. Aydinli M. Budd-Chiari Syndrome: Etiology, pathogenesis and diagnosis. World Journal of Gastroenterology. 2007;13(19):2693. doi:10.3748/wjg.v13.i19.2693
3. Figure 1: Doppler of hepatic vein demonstrating occlusion of multiple hepatic veins.

Introduction

Since the advent of the BAVENO VII consensus, Transient elastography (Fibroscan) has taken on a key role in the assessment of clinically significant portal hypertension (CSPH) and the prediction of decompensation and death. A liver stiffness measurement (LSM) ≤ 15 kPa associated with platelets ≥ 150 G/L excludes CSPH (NPV > 90%), while a LSM > 25 kPa is very much in favor of CSPH (PPV > 90%). CSPH remains possible in non-obese patients with LSM between 20 and 25 kPa with platelets < 150 G/L or LSM between 15 and 20 kPa with platelets < 110 G/L) but with a 40% risk of error.

Aims & Methods

We conducted this study to evaluate the reliability of transient elastography (TE) and platelet count in the diagnosis of CSPH, and to determine the extent of adherence to the consensus recommendations in our center.
This is a monocentric and retrospective study made in the gastroenterology and hepatology department of Mohamed Taher Maamouri Hospital in Nabeul, Tunisia, in which we collated reports of Fibroscans performed from March 2023 to March 2024.
We excluded patients with etiologies other than viral, alcoholic, or non-obese non-alcoholic steatohepatitis (NASH).
Platelet count and upper gastrointestinal endoscopy (EGD) data (if performed) were collected.
Data were entered and analyzed using SPSS version 27 software, with a significance level of 0.05.

Results

One hundred and fifty-nine Fibroscans were performed, of which 127 were included.
Women accounted for 64.6%, with a M/F sex ratio of 0.55. Mean age was 55.13 years [20-83].
The indications for Fibroscan were distributed as follows: 53.5% (68 patients) for non-obese NASH, 33.1% (42 patients) for HBV, 11.8% (15 patients) for HCV and only 2 cases for chronic ethylism.
The mean LSM value was 6.45 kPa [2-41.5], with thresholds distributed as follows; LSM <5 kPa in 70 patients (55.1%), LSM between 5 and 10 kPa in 44 patients (34.6%), LSM between 10 and 15 kPa in seven patients (5.5%), LSM between 15 and 20 kPa in two patients (1.6%), LSM between 20 and 25 kPa in a single patient, and LSM >25 kPa in three patients (2.4%).
The mean platelet count was 220 G/L [20-440], with a count > 150 G/L in 111 patients (87.4%), a count between 110 and 150 G/L in 13 patients (10.2%) and a count < 110 G/L in 3 patients.
Of all patients, 24 FOGDs were performed. Signs of Portal hypertension (PH) were noted in only 5 cases, represented by grade I esophageal varices.
In analytical study, hepatic elastography and platelet count were significantly correlated with the presence of endoscopic PH (p=0.009). Indeed, among patients with signs of endoscopic PH, 60% had a LSM > 25 kPa, 20% had a LSM between 15 and 20 kPa with a platelet count < 110 G/L and only 20% had a LSM < 10 kPa.
Furthermore, the consensus recommendations for the indication or not of EGD were not respected in our center (p=0.004); of all endoscopies performed 87.5% (21 EGD) were not indicated, and we noted one case where EGD was indicated but not performed.

Conclusion

Our study highlighted the recommendations of the latest BAVENO VII consensus regarding the reliability of transient elastography and platelet count in the evaluation of CSPH (p=0.009). This must be taken into consideration by practitioners in order to implement adequate preventive measures and to rationalize the indication of EGD which remains an inconvenient procedure for our patients.