Introduction

Celiac disease is a chronic, autoimmune disease that affects the small bowel in genetically predisposed persons precipitated by the ingestion of gluten. Celiac disease (CeD) and inflammatory bowel disease (IBD), principally Crohn’s disease (CD) and ulcerative colitis (UC) are among the most common immune-mediated gastrointestinal diseases.
Some studies have described the coexistence of the 2 diseases in the same patient.

Aims & Methods

The aims of the present study were to determine the prevalence of inflammatory bowel disease (IBD) and to elucidate the clinical features in patients with CeD with concomitant IBD.
We conducted a cross-sectional and single-center study. A total of 205 adults with CeD were included, and following up at the Gastroenterology unit of the Constantine University Hospital between 2015 and 2021. The diagnosis of CeD was made with the positive serology and histology of endoscopic duodenal biopsies and we identified those who were also diagnosed with IBD. The diagnosis of IBD associated to CeD was established based on clinical, endoscopic, histopathological, and radiological findings. Clinical, demographic, laboratory and morphological characteristics were analysed in these conditions. Osteodensitometry was performed on every patient with CeD and IBD.

Results

Among 205 patients with CeD, 14 had co-existent IBD (6,8%; n = 11 CD, n = 3 UC), their mean age at diagnosis of CeD was 29.7 ± 15.7 years. Females constituted 64,3%. The average delay of diagnosis between IBD and CeD was 6.4±3.8 years. The diagnosis of CeD preceded that of IBD in 35,7% (n=5) and 28,5% (n=4) of patients was concurrently diagnosed with IBD and CeD. Patients with CeD and concomitant IBD had a higher frequency of atypical symptoms of CeD (63,6%). Various extra-intestinal manifestations have been reported in 71,4% (aphthous stomatitis: 35,7%; depression: 42,8%). Osteoporosis was detected in 1 case with CD. Celiac disease serology was positive in all cases. The distribution of duodenal histology results according to Marsh-Oberhuber classification were 4/14 Marsh 3a, 6/14 Marsh 3b, 4/14 Marsh 3c. Other autoimmune disorders, including autoimmune thyroiditis (n=2) and type-1 diabetes (n=1). Of the patients diagnosed with CeD and CD, 7 had Ileocolonic involvement and only 2 had perianal disease. The dominant behaviour of CD was of the Stricturing type in 7 cases. Two patients with UC had extensive colitis. All patients were put on a gluten-free diet (GFD). IBD was treated with 5-aminosalicylic acid (n=1), immunomodulators (n=7) and biological therapy (n=6).

Conclusion

In our study of patients with CeD the prevalence of IBD was 6,8% (IC 95% 3,8%-11,2%). It’s higher than previously reported in a number of studies. CD was more common than UC. Patients with UC and CeD were more likely to have pancolitis.

Introduction

Recently, sub-classification of steatotic liver disease (SLD) has been updated by revising non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated steatotic liver disease (MASLD). In this new nomenclature, emphasis was on the etiology of SLD, primarily at factors of metabolic syndrome and alcohol intake. However, associations between MASLD and gastrointestinal tract cancers other than liver cancer in relation to alcohol intake still require further analysis.

Aims & Methods

We investigated the relationship between the incidence of three gastrointestinal tract cancers (esophageal, stomach, and colorectal) and MASLD or alcohol related-SLD in diabetic patients. Using a retrospective screening cohort of National Health Insurance Service, individuals with type 2 diabetes from 2009 to 2012 were enrolled with their disease status being monitored until 2021. Fatty liver index (FLI) score described by Bedogni et al. (2006) was used to stratify the probability of hepatic steatosis. No steatosis (NS), indeterminate steatosis (IS), and steatosis-probable (PS) group were defined as FLI score 0 to < 30, 30< to ≤60, and >60, respectively. SLD was assumed if FLI score ≥ 30, and MASLD was defined as having at least 1 adult criteria provided by the American Association for the Study of Liver Diseases (AASLD). 2,746,079 subjects were classified into following subgroups: group 1: no steatosis, group 2: MASLD alone, group 3: MASLD with other liver disease, group 4: MASLD with heavy alcohol intake (metALD, 30-60g/d for men and 20-50g/d for women), and group 5: alcoholic liver disease (alcohol intake ≥ 60g/d for men and ≥50g/d for women) with metabolic syndrome. Adjusted hazard ratios (aHR) for each gastrointestinal tract cancer were estimated by incorporating multivariate Cox proportional hazards model.

Results

Compared with group 1 (reference), group 2 showed increased risks of stomach and colorectal cancers (aHR [95% confidence interval (CI)]: 1.06 [1.04-1.09] and 1.17 [1.14-1.19] respectively), but a decreased risk of esophageal cancer (0.81 [0.74-0.88]). In all gastrointestinal tract cancers, the risk of developing cancer compared to group 1 tended to increase from group 3 to group 5 (aHRs in groups 3, 4, 5: 1.40, 1.74, 2.36 in esophageal cancer; 1.13, 1.20, 1.22 in stomach cancer; 1.24, 1.33, 1.34 in colorectal cancer, respectively; all p for trend < 0.0001). Subgroup analysis by probability of steatosis in non-drinkers showed that stomach and colorectal cancer risk was positively correlated with higher likelihood of liver steatosis (aHR for NS, IS, PS: 1.00, 1.05, 1.11 for stomach cancer and 1.00, 1.15, 1.27 for colorectal cancer, respectively, p for trend < 0.05). However, this correlation was not demonstrated in esophageal cancer (aHR for NS, IS, PS:1.00, 0.95, 1.08 for esophageal cancer).

Conclusion

In patients with diabetes, MASLD itself is associated with an increased risk of stomach and colorectal cancers but is likely associated with a reduced risk of esophageal cancer. Hepatic steatosis may be associated with higher risk of stomach and colorectal cancers, but not esophageal cancer. Amount of alcohol consumption is confirmed to increase the risk of these cancers regardless of the presence of SLD.

References

1. Rinella, Mary E. "Examining the Nomenclature Change From NAFLD and NASH to MASLD and MASH." Gastroenterology & Hepatology 19.11 (2023): 697.
2. Bedogni, Giorgio, et al. "The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population." BMC gastroenterology 6 (2006): 1-7.
3. Dabo, Bashir, et al. "The association between diabetes and gastric cancer: results from the Stomach Cancer Pooling Project Consortium." European Journal of Cancer Prevention 31.3 (2022): 260-269.
4. Lee, Hokyou, et al. "Metabolic Dysfunction–Associated Fatty Liver Disease Increases Colon Cancer Risk: A Nationwide Cohort Study." Clinical and translational gastroenterology 13.1 (2022): e00435.

Introduction

Celiac disease (CD) is an immune-mediated systemic disease, triggered by the ingestion of gluten, which only develops in genetically predisposed individuals. The main characteristics of the disease are the gluten-dependent small intestinal mucosal lesion, villous atrophy and crypt hyperplasia, and the production of the specific serum autoantibodies. The gold standard for diagnosis has been based on the biopsy findings. In 2012, new ESPGHAN diagnostic guidelines removed the necessity of duodenal biopsy in symptomatic children showing a high serum transglutaminase 2 titers (TG2-IgA) together with the presence of endomysial antibodies (EmA) and HLA DQ2 and/or DQ8.

Aims & Methods

Our aim was to assess the clinical outcome of the diagnostic change in children by comparing new serology-based diagnosed patients to the biopsy-based ones.
We conducted a retrospective analysis of data collected from the medical charts of the patients diagnosed during a four-year period, from 2010 to 2014, being a time overlapping the guideline change. From a total of 63 patients, 30 were biopsy-diagnosed and 33 diagnoses were based on serology only. Clinical data and laboratory parameters were compared between the groups at diagnosis and at follow-ups at 1 year, 2 years and at their latest follow-up visit during the gluten-free diet (GFD) treatment, median time 8.7 years for the serology-based group and 10 years for the biopsy-based group.

Results

Our results show clear improvement upon GFD in gastrointestinal symptoms in both groups. However, there was a general trend for better treatment outcomes in the biopsy-based group compared to the serology-based group at 1 and 2 years of follow-up. Body mass index Z score was in the biopsy group at baseline -1.5, at 1 year on GFD -0.2 and at 2 years -0.2. The corresponding results in the serology group was -1.51, -0.8 (p=0-056), and -1.35 (p=0.023). Anemia was observed in the serology group at one year as frequently (25%) as at baseline (26.7%) but in the biopsy group improvement from baseline was seen, 27.4% to 7.1 % of patients. At two years, anemia was present in 16.6% of patients. Ferritin values were significantly lower in the serology group at one year (27.5 µg/L vs 59, p=0.040) but not anymore at 2 years. After two years on GFD both TG2-IgA and EmA were often still above the cut-off for positivity in both diagnostic groups (serology group 58.3 % and 50% respectively and in the biopsy group somewhat less, 50% and 28.6% respectively). At long term, no anemia was present anymore. However, 4 children from serology group and 8 from the biopsy group showed antibodies above cut-off even after 8.7 and 10 years of treatment, respectively. Upon long-term follow-up the patients from the biopsy-proven group seemed to be more compliant with the follow-up visits and more adherent to the gluten-free diet.

Conclusion

Both clinical and laboratory results show slow recovery upon gluten-free diet. High percentage of autoantibody positivity still at 2 years on GFD indicates substantial amounts of gluten in the diet. Biopsy-proven patients seemed to have a faster recovery than the serology-diagnosed. Serological diagnosis also appears to negatively influence the adherence and compliance to treatment and follow-up. Novel (drug/vaccine) treatments adjunctive to GFD are an unmet need also in children. Duodenal mucosal recovery results on long-term GFD are warranted.

Introduction

In the absence of any globally approved pharmacotherapy, current guidelines recommend lifestyle modification and weight loss in people with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH). Semaglutide, a glucagon-like peptide (GLP)-1 analogue indicated for management of body weight and type 2 diabetes (T2D), is under investigation in MASH. However, T2D seems to reduce GLP-1 analogue-mediated weight loss in people with overweight/obesity.

Aims & Methods

This study evaluated the impact of T2D and other cardiometabolic parameters on weight loss in randomised controlled trials of subcutaneous semaglutide in MASLD including MASH. Data were taken from adults in NCT03357380 (MASLD; semaglutide 0.4 mg or placebo once daily [OD] for 72 weeks), NCT02970942 (MASH and fibrosis stage [F] 1–3; semaglutide 0.1, 0.2 or 0.4 mg or placebo OD for 72 weeks) and NCT03987451 (MASH, F4 and compensated liver cirrhosis; semaglutide 2.4 mg or placebo once weekly [OW] for 48 weeks). This post-hoc analysis pooled data for semaglutide
(0.4 mg OD and 2.4 mg OW) and placebo, with weight changes grouped by baseline T2D status (previously diagnosed or glycated haemoglobin [HbA1c] ≥ 6.5%, pre-T2D [HbA1c ≥ 5.7 – < 6.5%] or no T2D [HbA1c < 5.7%]). Mean on-treatment changes from baseline to 1 year were used to derive estimated treatment differences (ETDs) and 95% confidence intervals for semaglutide vs placebo. Impact of cardiometabolic factors including baseline fasting lipids, plasma glucose, diabetes duration and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were assessed.

Results

Of the 300 participants included, 209 (70%) had T2D, 51 (17%) pre-T2D and 40 (13%) non-T2D. ETDs ranged from – 9.8 kg in the pre-T2D group to – 11.6 kg in the non-T2D group; there was no significant difference between the non-T2D vs pre-T2D, pre-T2D vs T2D and non-T2D vs T2D groups in terms of weight change (Table). Weight change was not influenced by known diabetes duration, or baseline HOMA-IR or glucose and lipid levels.

Conclusion

Unlike previously reported differences in weight change in people with and without T2D, the presence of T2D did not influence efficacious weight loss with semaglutide in individuals with MASLD including MASH.

Disclosure

MJA is a consultant for, and has received speaker fees from, Novo Nordisk and Norgine.  
A-SS is an employee and shareholder of Novo Nordisk A/S.
MSP is an employee and shareholder of Novo Nordisk A/S.
MT is an employee of Novo Nordisk A/S.
MR is on advisory boards for and received speaker fees from Novo Nordisk.
TO has no interests to declare.

Introduction

Based on the Chicago classification, HREM diagnosis is classically based on metrics obtained with wet swallows carried out in the supine position. However, both patients and physicians often feel that this is not a physiological position to conduct the test as it may not translate to the real world experience. With the patient in the upright/sitting position, the test would more closely simulate real-life behaviour and may be safer for elderly patients at risk of aspiration.

Aims & Methods

In an Asian tertiary centre, a total of 104 patients had undergone high resolution esophageal manometry (HREM) with retrospective data analysis comparing both conventional supine position with the upright position. The latter is generally favoured by all patients as this represents the physiological posture during meals.

Results

Using 2-tailed paired sample T-test, comparison across all cases showed a consistently lower median Integrated Relaxation Pressure (IRP) [6.0 mmHg vs to 8.7 mmHg; p <0.01] and lower mean Distal Contractile Integral (DCI) [1463 mmHg/cm/sec vs 1864 mmHg/cm/sec; p =0.014] in the upright posture compared to supine position although the mean Distal Latency (DL) difference was not significant [6.21secs vs 6.27 secs; p =0.491]. During upright and supine position comparison respectively, subgroup analysis on subjects with normal HREM diagnosis showed even lower median IRP [4.9 mmHg vs 7.5 mmHg; p <0.01] and lower mean DCI results [1436 mmHg/cm/sec vs 1695 mmHg/cm/sec; p <0.01] with mean DL in this subgroup showing no significant statistical difference [6.29 secs vs 6.38secs; p=0.545]. The final HREM diagnosis in upright position is concordant with the conventional supine position up to 81.7% and showed an even higher concordance in terms of management similarity up to 98.1%. Only 2 cases (2/104) showed a significant discordance between supine and upright HREM diagnosis [normal HREM vs esophagogastric juntion –outflow obstruction(EGJ-OO) and hypercontractile esophagus vs normal HREM]. Minor diagnostic discordance [normal HREM vs ineffective esophageal motility (IEM)] was noted in 17/104 cases which had no major clinical impact on patients and may be overcome by adopting a lower cut-off for mean DCI for upright group.

Conclusion

In patients who are unable to perform HREM in supine position, adopting the upright position shows a high clinical concordance and may be considered a more physiological approach in the HREM protocol.

References

Riva CG, Siboni S, Ferrari D, Sozzi M, Capuzzo M, Asti E, Ogliari C, Bonavina L. Effect of Body Position on High-resolution Esophageal Manometry Variables and Final Manometric Diagnosis. J Neurogastroenterol Motil. 2020 Jul 30;26(3):335-343. doi: 10.5056/jnm20010. PMID: 32606256; PMCID: PMC7329148.

Introduction

Diet is an essential regulator of brain function, evidenced by longstanding associations between nutrient intake and neuronal function, synaptic plasticity, and neurotransmitter release. Recent studies have suggested that diet may impact mental health and cognition and even convey susceptibility to neurogenerative disease. However, there is little related neuroimaging evidence to date.

Aims & Methods

Our aim was to delineate the association between diet, brain structure and function. We studied 518 healthy participants from the Cambridge Centre for Aging and Neuroscience (CAM-Can) repository (261 male and 257 female, mean age 53 ± .79 years). Participants were clustered via their self-reported dietary intakes using K-means clustering. Resting-state functional, white matter tractography, and grey matter volumetry networks conditional to dietary cluster were analysed using network-based statistics, controlling for participant age and sex as nuisance covariates. Relevant clinical data comprising BMI and Hospital Anxiety and Depression Score (HADS) were compared between diet clusters using Welch’s t-test.

Results

Four distinct dietary intake patterns were identified: balanced, meat-predominant, vegetarian, and raw vegetable-predominant diets. Specific dietary types – balanced, meat-predominant and vegetarian – were associated with increased functional, grey matter or white matter connectivity between regions comprising the bilateral insula, frontomedial cortex (FMC) and bilateral anterior cingulate cortex (ACC) (p<0.04). A balanced diet was associated with significantly increased functional, structural, and white matter connectivity between frontal brain regions, including the orbitofrontal cortex (OFC), superior frontal gyri (SFG), and FMC (p=0.04) when compared to other diet clusters. A balanced diet was associated with a significantly reduced depression score (HADS-D) (p=0.03), compared to a meat-predominant one. The meat-predominant diet cluster was correlated with increased structural connectivity at the bilateral ACC (p=0.03) and significantly increased BMI (p=0.01), when compared to vegetarian diets.

Conclusion

In the largest study of its kind, we reveal the structural and functional connectomic brain associations of diet. Notably, the set of brain regions implicated have broader established roles across interoception, emotion, memory, reward and addiction. Our findings imply a possible physiological correlate for diet-induced changes in behaviour, weight, mood, and cognition previously observed in the literature, and pave the way for future research.

References

1.Zhang R, Zhang B, Shen C, Sahakian BJ, Li Z, Zhang W, et al. Associations of dietary patterns with brain health from behavioral, neuroimaging, biochemical and genetic analyses. Nat Ment Health. 2024 Apr 1;1–18.
2.Gaynor AM, Varangis E, Song S, Gazes Y, Noofoory D, Babukutty RS, et al. Diet moderates the effect of resting state functional connectivity on cognitive function. Sci Rep. 2022 Sep 27;12(1):16080.
3.Jensen DEA, Leoni V, Klein-Flügge MC, Ebmeier KP, Suri S. Associations of dietary markers with brain volume and connectivity: A systematic review of MRI studies. Ageing Res Rev. 2021 Sep 1;70:101360.
4.Rolls ET, Feng R, Cheng W, Feng J. Orbitofrontal cortex connectivity is associated with food reward and body weight in humans. Soc Cogn Affect Neurosci. 2023 Jan 1;18(1):nsab083.
5.Tan HE, Sisti AC, Jin H, Vignovich M, Villavicencio M, Tsang KS, et al. The gut–brain axis mediates sugar preference. Nature. 2020 Apr;580(7804):511–6.
6.Rolls ET. Functions of the anterior insula in taste, autonomic, and related functions. Brain Cogn. 2016 Dec 1;110:4–19.
7.Frank S, Kullmann S, Veit R. Food related processes in the insular cortex. Front Hum Neurosci. 2013 Aug 23;7:499.

Disclosure

No conflicts of interest.