Introduction

Inflammatory Bowel Disease (IBD), encompassing Crohn's Disease (CD) and Ulcerative Colitis (UC), shares chronic and inflammatory characteristics with Non-Alcoholic Fatty Liver Disease (NAFLD). While their precise pathogenesis remains unclear, emerging evidence implicates dysbiosis and metabolic changes. This study aims to investigate the association between IBD and NAFLD, focusing on metabolic syndrome and its nutritional implications

Aims & Methods

Objective: To evaluate the nutritional status and body composition in IBD patients, comparing groups with and without NAFLD, and identifying the associated factors.
Methods: A cross-sectional study was conducted, assessing clinical data, metabolic syndrome presence, nutritional status, and biochemical markers. Patients were categorized into IBD+NAFLD and IBD-only groups based on hepatic ultrasound findings. Statistical analysis included descriptive statistics and logistic regression.

Results

127 patients were included, comprising 58 CD and 69 UC, with a mean age of 45.56 years. Most patients were female and did not engage in physical activity. Patients were mostly in clinical remission and endoscopic activity. 58 patients (45.67%) had hepatic steatosis on ultrasound, forming the IBD+NAFLD group. The IBD+NAFLD group had higher BMI, fat mass, and all circumference values, Table 1, as well as a higher prevalence of hypertension (p=0.0446) and dyslipidemia (p=0.0377). It is noteworthy that, although most of these patients were classified as overweight by BMI, considering anthropometric data, most IBD+NAFLD patients were classified as eutrophic. 86.21% of patients in the IBD+NAFLD group met the criteria for MAFLD. No difference was observed regarding medication in use. Regarding biochemical tests, the IBD+NAFLD group had higher values of hematocrit (p=0.0023), liver enzymes (AST, p=0.0141 and ALT, p<0.0001), fasting glucose (p=0.0107), glycated hemoglobin (p=0.0146), basal insulin (p=0.0003), and triglycerides (p=0.0001), with lower HDL cholesterol (p=0.0101)

Conclusion

The study highlights a significant association between nutritional status and NAFLD in IBD patients. Those categorized as eutrophic had a higher prevalence of hepatic steatosis, potentially linked to dietary factors.

References

Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and
natural history of non‐alcoholic fatty liver disease and non‐alcoholic
steatohepatitis in adults. Alimentary pharmacology & therapeutics.
2011;34(3):274-285./ Silva A.F; Schieferdecker M.H; Amarante M. B. Ingestão alimentar em pacientes
com doença inflamatória intestinal ABCD, arq. bras. cir. dig. 24 (3) • Set 2011/ Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA.
2015;313(22):2263-73

Introduction

Short bowel syndrome (SBS) is a severe complication of extensive small intestinal resection, most commonly occurring in Crohn’s disease (CD), a chronic inflammatory disorder defined by transmural immune infiltration. Cytokines and chemokines are central mediators in the immune cascade driving intestinal inflammation and tissue damage^1,2. Despite advances in care, no biomarkers currently predict SBS onset or progression to intestinal failure (IF). Profiling systemic cytokine and chemokine signatures may thus offer novel insight into disease trajectory and risk stratification.

Aims & Methods

This study investigates circulating inflammatory mediators in patients with established IF/SBS and CD patients at high risk of progression. A total of 150 patients with CD were enrolled and stratified into five groups based on intestinal function and surgical history: A1, SBS with IF requiring parenteral nutrition (PN) or intravenous fluids; A3, SBS without IF and inactive disease; B, high risk of IF with multiple or extensive resections; C1, low risk for IF with no history of resection; and C2, low risk for IF with prior resection. Serum cytokine and chemokine profiles were quantified at baseline (T0) and after six months (T6) using the human 27-PLEX multiplex immunoassay.

Results

Serum cytokines and chemokines profiling at baseline (T0) and after six months (T6) revealed distinct inflammatory patterns across the study groups. Patients with SBS and IF (group A1) showed persistently elevated levels of IP-10, IL-12, MIP-1α, and G-CSF, reflecting sustained immune activation. Whereas, patients at high risk of IF (group B) displayed increased Eotaxin, bFGF, IL-15, and IL-6, indicative of subclinical inflammation and possible tissue remodelling.
A general reduction in cytokine levels was observed at T6, though anti-inflammatory mediators remained minimally modulated, suggesting ongoing low-grade inflammation. Comparisons between groups highlighted divergent cytokine signatures correlating with disease severity and nutritional support requirements.

Conclusion

These findings suggest that specific circulating cytokines may serve as potential biomarkers for early identification of patients at risk of IF. The differential expression patterns observed across groups support their relevance in stratifying disease severity in CD and SBS. Further large-scale studies are needed to validate these preliminary results and to fully establish their prognostic significance.
Funded by: 2.1 “Rafforzamento e potenziamento della ricerca biomedica del SSN”, finanziato dall’Unione europea – NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project “Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets” code: PNRR-MAD-2022-12376791.

References

1. Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019;50(4):992-1006. doi:10.1016/j.immuni.2019.03.017
2. Singh UP, Singh NP, Murphy EA, et al. Chemokine and cytokine levels in inflammatory bowel disease patients. Cytokine. 2016;77:44-49. doi:10.1016/j.cyto.2015.10.008

Introduction

Perianal fistulising Crohn’s disease (PFCD) affects up to 20% of patients with Crohn’s Disease (CD). PFCD can cause pain, purulent discharge and faecal incontinence, leading to significant morbidity and reduction in quality of life. The use of biologic therapy, antibiotics and surgical intervention remain the mainstay of management of perianal fistulas.

Aims & Methods

This study aims to review current practices in the management of PFCD across two large tertiary IBD centres. This retrospective cohort study assessed adult patients with PFCD between two tertiary Australian hospitals between 2006 to 2024. Patients with PFCD were identified using prescribing data. CD phenotype, therapy and fistula-related data were extracted. Biologic choice and therapeutic drug monitoring, antibiotic choice and duration, surgical intervention, and length of stay in hospital were monitored. Cross-sectional disease activity of perianal fistulizing disease was assessed at the time of data collection using clinical fistula symptom grade and radiological assessment were available. Clinical remission was defined as fistula symptom grade of 1 or less. Radiological remission was defined by healing fistula tracts or no active inflammation seen on MRI. The study was approved by the Central Adelaide Local Health Network Human Research Ethics Committee (HREC19145).

Results

Gender Male, n Female, n Age, y, median (IQR)	n = 57 30 27 40 (31-54)
Active Smoker, n (%)	14 (24.5)
Median length of clinical follow up, months, n (IQR)	46.5 (23.8-72.3)
Antibiotics Prescribed Metronidazole, n treated (%) Amoxicillin / Clavulanic acid, n treated (%) Others, n treated (%)	47 (68.1) 13 (27.7) 9 (4.2)
Duration of Antibiotics Metronidazole, median duration, days (IQR) Amoxicillin / Clavulanic acid, median duration, days (IQR) Others, median duration, days (IQR)	5 (5-7) 5 (5-10) 14 (7-14)
Biologic therapy Total patients on biologic therapy, n (%) Infliximab, n (%) Adalulimab, n (%) Ustekinumab, n (%)	56 (98.2) 43 (75.4) 11 (19.3) 2 (3.5)
Therapeutic Drug Monitoring (Infliximab) Infliximab level performed, n (%) Subtherapeutic (Infliximab level <10), n (%) Active disease and subtherapeutic (Infliximab level <10), n (%)	37 (86%) 30 (81.1%) 12 (40%)
Remission status Clinical Remission, n (%) - Defined as Fistula symptom grade of 1 or less Radiological Remission, n (%) - Defined as healing fistula tracts or no active inflammation seen on MRI	48 (84.2) 33 (57.8)
Subtherapeutic Therapeutic Drug Monitoring (All biologic agents) In Remission, n (%) Active Disease, n (%)	18 (56.2) 14 (43.8)

Table 1. Baseline characteristics

57 patients (median age, 40 years (31-54); 52.6% male) with PFCD were included in the study and followed over a median duration of 46.5 months (23.8-72.3). There were a total of 157 individual surgical procedures over the period, 2.75 per patient, most of which (94.2%) were examination under anaesthesia. Antibiotic therapy was dispensed for either perianal sepsis or an actively draining fistula in 26 patients, 2.65 number of courses per patient. The most common antibiotic prescribed was Metronidazole (68.1%), followed by Amoxicillin / Clavulanic acid (27.7%). The median duration of antibiotic therapy was 5 days (5-7) for Metronidazole and 5 days (5-10) for Amoxicillin / Clavulanic acid. There were 56 (98.2%) patients on biologic therapy. The most common biologic agent was Infliximab (75.4%), followed by Adalimumab (19.3%) and Ustekinumab (3.5%). At the time of analysis, 48 patients (84.2%) were in clinical remission and 33 patients (57.8%) were in radiographical remission. In patients treated with infliximab, 37/43 (86%) had therapeutic drug monitoring performed. Amongst these, 30 (81.1%) had subtherapeutic levels (defined as Infliximab level < 10), with 12/30 (40%) of patients having active PFCD.

Conclusion

Across two tertiary IBD centres, management of PFCD is variable and not in keeping with current guidelines. Short courses of antibiotic therapy were used, and the majority of patients had subtherapeutic drug levels when tested. Optimising outcomes for patients with PFCD requires awareness of best practice and a multidisciplinary team approach.

Introduction

Piecemeal endoscopic mucosal resection (pEMR) is the preferred treatment for large non-pedunculated colorectal polyps (LNPCPs)[1,2]. A major limitation of pEMR is residual or recurrent adenoma (RRA), which was reported to in 15%-30% of cases at first surveillance colonoscopy (SC1)[3], performed 3-6 months after the index procedure, but is reduced to the range of 3%-5% by applying ablative measures to the post-EMR resection margin[4].

Aims & Methods

This study aimed to evaluate the effects of late SC1 on RRA.
This is an analysis of a prospectively collected cohort of adult patients referred for pEMR at two academic centers in Israel, from 2016 to 2023. We included all patients who underwent pEMR of LNCPCs and completed SC1.
We compared outcomes between patients who completed early SC1 at 3-6 months following the index procedure with patients who completed late SC1 later than 6 months. All procedures and surveillance colonoscopies were performed by experienced endoscopists trained in pEMR using high-definition scopes. EMR was followed by thermal ablation of the entire mucosal defect margin with snare soft tip coagulation, as previously described[4].
Scar evaluation at SC1 was performed with high-definition white light and chromoendoscopy. Our primary endpoint was RRA at SC1.
Analyses were performed per lesion. We compared baseline parameters and outcome rates between groups, and performed multivariate analysis to assess the adjusted association of months to SC1 with RRA.

Results

We analyzed 516 lesions that underwent index pEMR resection and subsequent SC1. Baseline parameters and recurrence rates are presented in Table 1. The early SC1 group (n=371) underwent SC1 at a mean of 5.1 months versus a mean of 11.1 months in the late SC1 group (p<0.01; Table 1). Polyp size in the early SC1 group was significantly larger than that in the late SC1 group (mean size 35.9 mm [SD 13.9] vs. 32.1 mm [SD 12.4], p<0.01; Table 1). The distribution of lesion location, granularity differed between the groups (Table 1). However, there were no significant differences in lesion Paris classification or rates of high grade dysplasia (Table 1).
We found no statistically significant difference in the rate of recurrence at SC1 between the two groups (6.3% in the standard group versus 4.8% in the delayed group, p=0.64). Additionally, a sub-analysis comparing the early SC1 group to patients with very late SC1 (>12 months – mean time to SC1 17.9 (SD [5.4] months) and did not reveal significant difference in recurrence at SC1 (6.2% in the early SC1 vs 6.3% in the very late group, p=1).
Multivariate analysis, adjusted for lesion size, location, and high-grade dysplasia, showed that time to SC1 was not significantly associated with RRA (odds ratio 1.05, 95% confidence interval 0.98-1.13).

TABLE 1. Comparison of baseline variables and outcome between the early and late SC1.

	Early SC1 (n=371)	Late SC1 (n=145)	P value
Time to SC1, months	5.1 (1.1)	11.1 (5.6)	<0.01
Age, years	65.4 (10.4)	68.0 (10.2)	0.01
Female, n (%)	168 (45.4)	51 (35.2)	0.05
Lesion Size, mm	35.9 (13.9)	32.1 (12.4)	<0.01
Distal location, n (%)	111 (29.9)	29 (20.0)	0.03
Granular morphology, n (%)	230 (63.7)	74 (53.2)	0.04
Paris IIb/IIc/III, n (%)	39 (10.5)	15 (10.3)	1.00
High grade dysplasia, n (%)	97 (26.1)	33 (22.8)	0.49
Recurrence at SC1, n (%)	23 (6.2)	7 (4.8)	0.70

SC1, First surveillance colonoscopy

Conclusion

Late SC1 is not associated with an increased RRA. Hence, we suggest that high-quality pEMR with margin ablation may alleviate the need for early SC1, thereby reducing healthcare and patient burdens. Further interventional studies are required.

References

[1] Ferlitsch M, Moss A, Hassan C, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy 2017; 49: 270–297. doi:10.1055/S-0043-102569/ID/JR15335-1/BIB
[2] Shaukat A, Kaltenbach T, Dominitz JA, et al. Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2020; 159: 1916-1934.e2. doi:10.1053/j.gastro.2020.08.050
[3] Belderbos TDG, Leenders M, Moons LMG, et al. Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal lesions: Systematic review and meta-analysis. Endoscopy 2014; 46: 388–400. doi:10.1055/S-0034-1364970/ID/JR910-7/BIB
[4] Klein A, Tate DJ, Jayasekeran V, et al. Thermal Ablation of Mucosal Defect Margins Reduces Adenoma Recurrence After Colonic Endoscopic Mucosal Resection. Gastroenterology 2019; 156: 604-613.e3. doi:10.1053/j.gastro.2018.10.003

Disclosure

The authors report no conflict of interests