Introduction

Intestinal ultrasound (IUS) is a non-invasive, reproducible, low-cost technique for the assessment of intestinal diseases.¹
Crohn's disease (CD) and irritable bowel syndrome (IBS) are two of the major causes of chronic diarrhoea and abdominal pain in high-income countries.² IBS, especially in the diarrheal (IBS-D) or mixed (IBS-M) variants, has clinical features similar to those of CD.
The role of IUS in the diagnosis and monitoring of CD is well established,^{3, 4} whereas only scanty data are available on IBS. Current IBS guidelines do not recommend the use of IUS even to distinguish between IBS-D or IBS-M and CD.^{5, 6}

Aims & Methods

The aim of this two-gate diagnostic study was to assess the accuracy of IUS in discriminating between IBS-D or IBS-M and CD in patients presenting with similar symptoms.
In a high-volume tertiary Centre, consecutive patients symptomatic for chronic diarrhoea and abdominal pain underwent IUS performed by three experienced gastroenterologists.
In the group with clinically active CD, patients had a previous diagnosis based on clinical, biochemical, endoscopic, radiologic and histologic criteria, while in the IBS group subjects had a previous diagnosis based on Rome IV Criteria.
Bowel wall thickness (BWT) of the terminal ileum, ascending colon, transverse colon and descending colon/sigma was evaluated using two cut-offs of 3 mm and 4 mm.⁷ Enlarged lymph nodes, mesenteric fat hypertrophy, bowel wall stratification and submucosal vascularity were also assessed.
The diagnostic accuracy of IUS in discriminating between the two groups was estimated in terms of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and overall accuracy (OA) (Table 1).

Results

A total of 50 patients with IBS (62% female, mean age 41 years, SD ± 13 years, 54% IBS-D) and 50 subjects with CD (44% female, mean age 47 years, SD ± 17 years) were enrolled.
Forty-nine patients with IBS (98%) and 8 patients with CD (16%) and had a BWT < 3 mm. 49 patient with IBS (98%) and 12 patients with CD (24%) had a BWT < 4 mm.
Sensibility, specificity, LR+ and LR- of BWT < 3 mm were 98%, 84%, 6.13 and 0.02, respectively.
Sensibility, specificity, LR+ and LR- of BWT < 4 mm were 98%, 76%, 4.08 and 0.03, respectively.
BWT with 3 mm and 4 mm cut-offs showed an OA in discriminating between CD and IBS-D or IBS-M of 91% and 87%.
The absence of altered IUS parameters had 94% OA in discriminating between CD and IBS (Table 1).

Conclusion

IUS seems able to discriminate between IBS-D or IBS-M and CD in patients with chronic diarrhoea and abdominal pain. Particularly, a BWT < 3 mm may rule out the presence of clinically active CD and support the diagnosis of IBS. On the other hand, a BWT > 3 mm or a single altered ultrasound parameter might raise suspicion of CD and justify further testing. Cross-sectional studies are needed to confirm these preliminary results.

References

[1] Bryant RV, et al. Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application. Gut 2018;67(May (5)):973–85.
[2] Arasaradnam TP, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut vol. 67,8 (2018): 1380-1399.
[3] Castiglione F, et al. Noninvasive diagnosis of small bowel Crohn’s disease: direct comparison of bowel sonography and magnetic resonance enterography. Inflamm Bowel Dis 2013;19:991–8.
[4] Maaser C et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. Journal of Crohn's & colitis vol. 13,2 (2019): 144-164.
[5] Vasant, Dipesh H et al. British Society of Gastroenterology guidelines on the management of irritable bowel syndrome. Gut vol. 70,7 (2021): 1214-1240.
[6] Savarino E et al. “Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility.” United European gastroenterology journal vol. 10,6 (2022): 556-584.
[7] Fraquelli M, et al. Role of US in detection of Crohn disease: meta-analysis. Radiology. 2005;236(1):95-101.

Introduction

MASLD patients is increasing worldwide and the clinical outcomes of different phenotypes had shown varied especially the occurrence of of liver related events (LRE) or major cardiovascular events (MACE)(Eslam M, et al. Hepato Inter 2020, 14:889–919) In addition, the prognostic factors for LRE. or MACE. are not well studied.

Aims & Methods

Aims: We aimed to study the rate of LRE. or MACE and the predictors for LRE. Or MACE. in MASLD patients with liver biopsy proven.
Methods: In a single-tertiary-center prospective cohort, we collected data of MASLD patients with biopsy-proven who were followed up of at least 1 years at King Chulalongkorn Memorial Hospital during 2005-2022. The primary outcome was the presence of LRE. or MACE. which included cirrhotic complications: acute decompensations; EV/GV bleeding, ascites, hepatic encephalopathy or HCC or acute complications requiring liver transplantation or death. MACE was defined by the occurrence of stroke or acute coronary disease or myocardial infarction. Related baseline characteristics, LSM, FIB-4, and liver biopsy were collected.

Results

Among 286 MASLD patients, the MASLD patients with mean age of 50.1 +/- 14.5 years old (range 19-80 yr.) Male and female were 44% and 56 % respectively. MASLD patients were categorized into 3 groups which were type 2 diabetes mellitus (T2DM) in 119 (41.6%), overweight or obese group in 149 (52.1%), and lean MASLD (BMI<23) in 18 (6.3%). Their baseline characteristics were shown in Table 1.
The average BMI was 41.3 kg/m² (range 19.1-88.7). Other metabolic abnormalities were hypertension in 165 (57.7%), and dyslipidemia in 157 (54.9%). There were 6 cirrhotic cases (2.1%) at diagnosis. Presence of advanced liver fibrosis (TE>12KPA) was found in 15 cases (5.2%). After a mean follow-up of 9.5 years (range 1-19); there were 11 cases (3.8%) developed coronary artery disease and 3 cases (1%) developed stroke. LRE. were present in 7 cases (2.4%) which included acute decompensation (3 cases; 1%), HCC (3 cases; 1%), and death (1 cases; 0.3%). The overall complications of LRE. or MACE. were present in 16 cases (5.6%). By using multivariate analysis, the predictors of LRE. or MACE. were in presence of hypertriglyceridemia (aOR 1.01 (1.00-1.01); p =0.002) and older age (aOR 1.06 (1.01-1.11); p =0.023).

Conclusion

The overall complication of LRE. or MACE. was not uncommon (5.6% of this cohort with a mean follow-up of 9.5 years). Older age and hypertriglyceridemia were predictors of LRE. or MACE. occurrence.

References

Eslam M, et al. Hepato Inter 2020, 14:889–919.

Introduction

We lack reliable biomarkers to identify patients with inflammatory bowel disease (IBD) at a greater risk of severe disease course. With emerging evidence that early step-down treatment in severe patients leads to better disease outcomes, alongside worries about overtreatment of mild patients, there is a clinical need to identify such biomarkers.

Aims & Methods

In this study, we explore genetic variants associated with severe disease course for ulcerative colitis (UC) in a nationwide cohort of 4491 patients from Denmark.
We genotyped 4491 patients with UC (4153 from Danish birth blood spot archive; 338 from NorDIBD regional cohort), linking them with registry data capturing medical interactions throughout patients’ lifetimes. Patients who required 2+ IBD-related hospitalizations, 2+ IBD-related major surgeries, 1 IBD-related hospitalization and 1 IBD-related major surgery or use of systemic corticosteroids (≥5000 mg) in the first 3 years of diagnosis were defined as severe. We conducted a genome-wide association study comparing severe patients (N=1203) to those with a less severe disease course (N=3288).

Results

The GWAS identified a signal within the HLA region, with the HLA-DRB1*01:03 allele driving the association (OR=3.30 [2.23-4.87], P=2.08×10^-9, UC carriage rate=2.8%). We did not observe an association with CD severity in a similarly ascertained cohort of 3688 individuals (P=0.79).
Remarkably, carriage of DRB1*01:03 was associated with a seven-fold increase of major surgery risk (OR=7.05 [4.55-10.91], P=2.31×10^-16) (Table 1). At the point of diagnosis, carriage of DRB1*01:03 was associated with higher CRP levels (β=2.68, P=1.70×10^-7), f-cal levels (β=1.92, P=4.42×10^-3) and a higher rate of hospitalization at diagnosis (OR=1.64, P=0.014), suggesting that the effect on severity is not limited to disease progression.

Conclusion

In this large-scale, unselected nationwide cohort study, we find that HLA-DRB1*01:03 is a biomarker of UC disease course that is associated with a more severe presentation at diagnosis, as well as higher subsequent risk of surgery and hospitalization. Demonstrating the association at a genome-wide significance level for the first time, this study revitalizes findings from smaller studies at the beginning of the genetic era which explicitly recruited severe patients and made estimating carriage effects difficult.
While HLA-DRB1*01:03 is a low-frequency allele, patients who carry it are at a much higher risk of severe UC. As the cost of typing a single HLA allele is low (under 50 EUR) and several pharmacogenetic variants are beginning to be tested at diagnosis, we argue that it is a valuable addition to the arsenal of personalized healthcare tools.