Introduction

Primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed under the age of 6 years (i.e., VEO-IBD) may have unique characteristics and disease course. We aimed to analyze the characteristics and natural history of children with VEO PSC-IBD and compare them to children diagnosed with PSC-IBD at an older age.

Aims & Methods

This was a multicenter, retrospective, study evaluating patients diagnosed with both IBD and PSC before (VEO-PSC-IBD) or after the age of 6 years (PSC-IBD), followed at 14 centers affiliated with the Porto IBD Interest group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every six months thereafter for a minimum follow-up of 12 months. IBD-related (clinical remission, need for systemic steroids, therapy escalation and surgery) and PSC-related outcomes (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, or death) were analyzed at 1, 3 and 5 years.

Results

A total of 69 children with both IBD and PSC were included: 28 with VEO PSC-IBD [median age 5.2 years, 21 UC (75%), 4 IBDU (14%) and 3 (15%) CD] and 41 with PSC-IBD [median age 15.7 years, 34 UC (83%), 6 IBDU (1.5%) and 1 (0.2%) CD]. IBD was diagnosed prior to PSC in 28 of the 69 patients (40%), simultaneously in 30 (43%), and after PSC in 11 (16%), with no significant differences between VEO PSC-IBD and PSC-IBD. Most patients with UC presented with extensive disease at diagnosis (89% in VEO PSC-UC vs. 89% in PSC-UC, p = 0.72). Both groups presented most often with mild intestinal disease at diagnosis (mean PUCAI of VEO IBD-PSC 34±16, vs 31±19 of IBD-PSC, p=0.11; mean PCDAI 31±33 vs. 21±27, respectively, p=0.14). A higher number of VEO-IBD-PSC patients were diagnosed with autoimmune sclerosing cholangitis than older children [24 (86%) vs. 27 (66%) PSC-IBD, p=0.04], whereas no other differences were found for PSC-related variables. During follow-up, no significant differences were found in major IBD outcomes. The risk of developing biliary strictures and infective cholangitis was lower in the VEO-PSC-IBD group (Log-rank p=0.02 and p=0.02), while no difference was found for portal hypertension and liver transplantation at 5-year follow-up. No cases of cholangiocarcinoma or death were found.

Conclusion

This study is the first to focus on age-dependent PSC-IBD features in the pediatric population. IBD-PSC has similar baseline characteristics whether diagnosed as VEOIBD or thereafter. However, a milder disease course in terms of biliary complications characterize the subcohort of patients diagnosed at an earlier age.

Introduction

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory bowel disease, whose cause involves the interaction between genetic and environmental factors. At present, the pathogenesis of IBD has not been fully understood. Although there is a recognized link between immune response and IBD, the causal relationship between circulating immune cell counts and IBD remains controversial.

Aims & Methods

This study aimed to elucidate the causal relationship between genetically predicted circulating immune cell counts and IBD. We conducted a bidirectional two-sample Mendelian randomization (MR) study using aggregated statistics from genome-wide association studies. The causal relationship between five circulating leukocytes cells (monocytes, lymphocytes, eosinophils, basophils and neutrophils) counts and IBD, including Ulcerative colitis (UC) and Crohn's disease (CD) was analyzed. Inverse variance weighting (IVW) was used as the primary MR analysis method, and horizontal pleiotropy test and heterogeneity test were used to ensure the stability of the results.

Results

Our findings indicated that monocytes, lymphocytes, eosinophils, and basophils count were not significantly associated with IBD, however, elevated circulating neutrophils count was significantly associated with higher risk of IBD [odds ratio (OR): 1.002; 95% confidence interval (CI): 1.001–1.003; p = 0.009] and UC [OR: 2.465; 95%CI: 1.236–4.916; p = 0.01]. In addition, we also found that IBD [ OR: 12.07; 95% CI: 1.909-76.316; P = 0.008] and UC [OR: 2.465; 95% CI: 1.236 - 4.916; P = 0.01] were significantly associated with higher circulating neutrophils count in reverse MR.

Conclusion

This MR study provides genetic evidence for the causal relationship between the genetically predicted increase in circulating neutrophils count and the risk of IBD (UC and CD). This finding stresses the need for further exploring physiological functions of neutrophils in order to develop effective strategies against IBD.

Disclosure

The authors state that the study was conducted in the absence of any business or financial relationships that could be interpreted as potential conflicts of interest.

Introduction

Immunomodulators and biologicals play an essential role in current IBD management, but are associated with increased risk of infections. In light of the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. Post-marketing surveillance studies are pivotal to assess infection risk, yet mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. However, mild and moderate infections take longer to clear in immunosuppressed patients, have been reported to be the most burdensome adverse drug reaction according to patients, and can negatively influence drug adherence.

Aims & Methods

Aim: To assess the incidence of all infections and identify risk factors for the development of infections in IBD patients.
Methods: We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. [1] The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients and using the PRIQ which was implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for infections.

Results

In total, 629 IBD patients (n=346 CD, n=283 UC, 58.3% female, mean age at cohort entry 48.3 years [SD 14.8], mean disease duration 12.4 years [SD 10.8]) were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up. This resulted in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively. Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections types, respectively (Table 1). Compared to patients without treatment, patients on immunosuppressive treatment more frequently experienced infections of any severity (mild vs. no treatment: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p<0.001, moderate vs. no treatment: IRR 1.42 [95%CI 1.20-1.69] p<0.001). On multivariable logistic regression, female sex (mild adjusted odds ratio [aOR] 1.96 [95%CI 1.38-2.79]; moderate aOR 1.71 [95%CI 1.15-2.54]), smoking status (mild aOR 1.66 [95%CI 1.15-2.41]; moderate aOR 1.86 [95%CI 1.05-3.28]), higher BMI (moderate aOR 1.05 [95%CI 1.02-2.00]), and more comorbidities (mild aOR 2.41 [95%CI 1.46-3.98]; moderate aOR 1.82 [95%CI 1.07-3.11]) were all significantly associated with the development of mild and moderate infections.

Conclusion

​In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.

References

[1] Rezazadeh Ardabili A, van Esser D, Wintjens D, et al. Development and validation of a remote monitoring tool for assessment of mild, moderate, and severe infections in Inflammatory Bowel Disease [published online ahead of print, 2023 Feb 16]. J Crohns Colitis. 2023;jjad023. doi:10.1093/ecco-jcc/jjad023

Disclosure

M.P. reports grants and non-financial support from Falk Pharma, grants from European commission, grants from ZonMw (Dutch national research fund), grants and non-financial support from Takeda, grants and non-financial support from Johnson and Johnson, grants and non-financial support from Abbvie, non-financial support from Ferring, non-financial support from Immunodiagnostics, non-financial support from MSD, all outside the submitted work. D.J. reports grants from Top Knowledge Institute (Well on Wheat), grants from Horizon 2020 DISCOvERIE, grants from NWO-CCC Partnership program (Carbokinetics), all outside the submitted work. Z.M. reports grants form MLDS, Niels Stensen Fellowship and Galapagos. A.v.B. has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Galapagos, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from Pfizer, TEVA, Eurostars funding, ZonMw, all outside the submitted work.
The other authors have nothing to disclose relevant to this publication.

Introduction

Patients diagnosed with inflammatory bowel disease (IBD) may have damage in different parts of the gut. The development of this disease involves an intricate interaction between a host with genetic susceptibility, environmental factors, an imbalanced immune response, and intestinal microbiota. Several studies have revealed discrepancies in the composition of gut microbiota between IBD patients and healthy individuals, especially concerning microbial diversity and relative abundance of specific bacteria. Nonetheless, previous research typically involves patients who have undergone immunosuppressive treatment, potentially altering the microbiota and affecting the integrity of study findings.

Aims & Methods

The aim of this study was to elucidate the differences in the microbiota of newly diagnosed patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy controls (HC), based on the location of the affected area. Stool samples were obtained from IBD patients who had not yet initiated treatment for the disease, and from HC. Each sample underwent shotgun metagenomic sequencing, followed by bioinformatic analysis using the Cutadapt, Kraken2, and Bracken programs. Shannon index (α-diversity) and Bray-Curtis dissimilarity (β-diversity) were used as tests of within-species diversity and within-group diversity, respectively.

Results

We included 103 patients with CD, 144 with UC and 49 HC. Patients with CD, which have been classified depending on disease location (ileal, colonic and ileocolonic), showed lower α-diversity compared to HC in each subgroup, showing the lowest index in those with ileocolonic location. In UC patients, divided according to disease extension (proctitis, left-sided colitis and extensive colitis), those with extensive involvement, exhibited the lowest α-diversity compared to HC and other groups. β-diversity in CD patients revealed the highest differences between the comparisons ileal vs ileocolonic and colonic vs ileocolonic, suggesting that patients with ileocolonic pattern showed a more different microbiota profile compared to the other groups studied; however, there were no differences in UC patients. Examination of taxonomic abundance revealed a decrease in Phocaeicola coprocola and several species of Adlercreutzia, and an increase in Shigella flexneri, in CD patients, compared to HC. In UC patients, an increase in Toxoplasma gondii and Gemella morbillorum was observed in all three extension subgroups compared to HC. However, several species of Adlercreutzia and Alistipes were decreased in patients with extensive colitis compared to HC.

Conclusion

Our data suggest that newly diagnosed CD and UC patients showed relevant differences in the microbiota depending on the location of the disease, with a reduction in beneficial genus such as Adlercreutzia and Alistipes, and an increase in pathogenic species.

Introduction

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting.

Aims & Methods

The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD.

Results

In a retrospective study, we examined the medical records of 5,739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022.
Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in general population in northern Italy in 2021 was 0.18% (P = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 MS patients, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (P = 0.004). As for therapy, significant differences were found on mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, P < 0.0001) and anti-TNF treatment (0% cases vs 26.6% controls, P = 0.03, respectively) at the time of MS diagnosis. Moreover, Kaplan-Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (P = 0.02).

Conclusion

In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone.

Introduction

The enhancement of the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has become a major therapeutic target in the management of this disease. Sexuality is one of its main determinants. However, in Tunisia, there is little data on sexual dysfunction (SD) and fertility among IBD patients.

Aims & Methods

The aim of this study was to determine the incidence and the factors associated with SD during IBD. We conducted a cross-sectional study including patients with IBD followed at the Gastroenterology Department of Charles Nicole Hospital between July and December 2020. Sexual function was assessed by the Female Sexual Function Index (FSFI) score in women and by the International Index of Erectile Function (IIEF) in men. Scores assessing patients ‘overall QoL were calculated: Hospital anxiety and depression scale (HADS), Fatigue Severity Scale (FSS), and Short Inflammatory Bowel Disease Questionnaire (S-IBDQ). All patients gave oral informed consent before answering the questionnaires.

Results

A total of 65 patients were included of whom 72.3% had CD and 27.7% had UC, with a mean age of 47.58±10.18 years and sex ratio (M/F) of 0.44.
SD was found in 73.3% of women according to the FSFI and in 15% of men according to the IIEF-15. Erectile dysfunction (ED) was observed in 40% of patients based on the IIEF-5.
Female gender was a significant factor of SD (p<0.001; OR 15.6; CI [3.9-62.8]).
An analytical statistical study was conducted, showing factors associated with SD in the female patient group only.
Our study showed that the factors associated with the presence of female SD were age (p=0.018), absence of professional activity (p=0.034), length of marriage (p=0.022), presence of probable or overt depression (p=0.01), fatigue (p=0.042), impaired QoL judged by the S-IBDQ (p=0, 042), the four domains of the S-IBDQ (bowel symptoms (p=0.04), general signs (p=0.011), emotional domain (p=0.004), social domain (p=0.013)), IBD-disk score (p=0.007), and IBD-disk domains (sexual activity (p<0.001), emotion (p=0.001), energy (p=0.016), and joint pain (p=0.015)).
There were no factors that appeared to be associated with male SD. Meanwhile, we found a statistically significant association between men's perception of impaired sexuality due to IBD and the presence of ED (p=0.004; OR=33; CI [2.4-443.6]).
In multivariate analysis, the factors independently associated with female SD were the duration of marriage (p=0.018; OR 3.58; CI [1.43-7.83]), the presence of suspected or overt depression (p<0.001; OR 12.6; CI [1.82-72.52]) and fatigue (p=0.032; OR 11.8; CI [1.61-96.7]).

Conclusion

Our study shows that sexual disorders are frequent in IBD patients, especially in women. A multidisciplinary management involving gastroenterologists, psychologists, and sexologists is sometimes necessary in these young patients, in order to improve their QoL.

Introduction

Prior studies suggest an increased risk of non-alcoholic fatty liver disease (NAFLD) in patients (pts) with inflammatory bowel disease (IBD). There is no data available on the risk of cirrhosis in IBD. Our aim was to investigate the risk of cirrhosis (compensated or decompensated) in IBD pts compared to a matched non-IBD population in a population-based cohort.

Aims & Methods

A registry-based cohort study was conducted in the Danish health registries (including the pathology register) using data, between (and including) 1998 and 2018. Incident IBD was identified using ICD-8/10 codes for Crohn’s disease (CD) or ulcerative colitis (UC), with two IBD registrations up to two years apart, living in Denmark for at least one year prior to their first IBD registration and without a diagnosis of cirrhosis prior to their IBD registrations. Those with IBD were matched 1:10 to non-IBD persons on the basis of sex, age, calendar year, and the municipality of residence. Persons were followed from index date (IBD diagnosis date/matching date) until a diagnosis of cirrhosis (study outcome), death, emigration, or end of follow-up, whichever came first. The diagnosis of cirrhosis, including both compensated and decompensated cirrhosis, and the underlying etiology, were recorded by ICD-8/10 and SNOMED codes. Kaplan-Meier approach was used to calculate the cumulative incidence of cirrhosis and Cox proportional regression analysis to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for cirrhosis among pts with IBD, compared to the non-IBD population.

Results

In a study population of 495,220 persons, a total of 2,741 cirrhosis cases were identified (median [IQR] time in years between index date and diagnosis of cirrhosis: 6.3 [3.0-10.7]), with a higher proportion of cases among pts with IBD (N = 45,020) compared to non-IBD persons (0.9% vs. 0.5%, respectively). After adjusting for sex, age, and index year, pts with IBD had a higher risk of cirrhosis, compared to non-IBD persons (adjusted HR (95% CI): 1.84 [1.65 – 2.04]). Cirrhosis was diagnosed on the basis of liver biopsy and/or imaging (ultrasound, CT or MRI) in 77.3% of IBD pts vs. 69.3% of non-IBD persons. The leading etiology of cirrhosis was NAFLD (51.6%) followed by alcohol (39.0%). The risk of cirrhosis among IBD pts (compared to non-IBD persons) was more pronounced among younger persons (adjusted HR (95% CI): 3.08 [2.45-3.87] among ≤ 40 years of age; 1.63 [1.45-1.84] among > 40 years of age, p-value <0.001) and CD pts (adjusted HR (95% CI): 2.20 [1.80-2.67] among CD; 1.72 [1.52-1.95]; among UC, p-value 0.0402). The risk was also consistent across the year of cohort entry (IBD diagnosis year/index year): 1998-2001 (794 events, 1.37 [1.07-1.66]), 2002-2005 (776 events, 1.98 [1.63-2.40]), 2006-2009 (612 events, 1.94 [1.56-2.41]), 2010-2013 (378 events, 2.01 [1.53-2.64]), 2014-2018 (181 events, 2.89 [2.03-4.10]).

Conclusion

IBD pts had a higher incident risk of cirrhosis compared to matched non-IBD persons, especially with age at IBD diagnosis ≤ 40 years and those with CD. These data point towards a need for focused screening for cirrhosis among IBD pts, especially in certain risk groups.