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Intestinal fibrosis, which is usually the consequence of chronic inflammation, is a common complication of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. In the past few years, substantial advances have been made in the areas of pathogenesis, diagnosis and management of intestinal fibrosis. Of particular interest have been inflammation-independent mechanisms behind the gut fibrotic process, genetic and environmental risk factors (such as the role of the microbiota), and the generation of new in vitro and in vivo systems to study fibrogenesis in the gut. A huge amount of work has also been done in the area of biomarkers to predict or detect intestinal fibrosis, including novel cross-sectional imaging techniques. In parallel, researchers are embarking on developing and validating clinical trial end points and protocols to test novel antifibrotic agents, although no antifibrotic therapies are currently available. This Review presents the state of the art on the most recently identified pathogenic mechanisms of this serious IBD-related complication, focusing on possible targets of antifibrotic therapies, management strategies, and factors that might predict fibrosis progression or response to treatment.Intestinal fibrosis is an important feature of inflammatory bowel disease (IBD) that remains poorly understood. Here, D’Alessio and Ungaro et al. review the cellular and molecular mechanisms contributing to intestinal fibrosis and discuss future therapeutic strategies for IBD-related fibrosis.

Ulcerative colitis (UC) is a chronic relapsing disorder of the colonic tract, characterized by a dysregulated innate and adaptive immune response to gut microbiota that contributes to the perpetuation of intestinal inflammatory processes. The Interleukin (IL) 23/IL17 axis has been reported to play a key role in UC pathogenesis promoting Th17 cells and cytokines-related immune response. Recently, the blockade of IL23/IL17 pathways has been raised enormous interest in the treatment o several chronic inflammatory disorders. In this review, we summarize the emerging results from clinical trials that evoked both promise and discouragement in IL23/IL17 axis in the treatment of UC. Targeting IL23 p40 through Ustekinumab results safe and effective to induce and maintain clinical remission, low inflammatory indexes, mucosal healing, and a better quality of life. Studies targeting IL23 p19 through Mirikizumab, Risankizumab, Brazikumab and Guselkumab are still ongoing. To date, no clinical studies targeting IL17 pathway are ongoing in UC. IL-17 targeting is thought to have a context-dependent biological effect, based on whether cytokine is selectively targeted or if its function is dampened by the upstream block of IL23.

Background: The vaccination status of patients with inflammatory bowel disease (IBD) should be investigated before starting any treatment, and patients should eventually be vaccinated against vaccine-preventable diseases (VPDs). Patients with IBD may have suboptimal vaccination rates. The aim of this study was to evaluate the vaccination coverage, attitude towards vaccinations, and determinants among an Italian cohort of patients with IBD. Methods: AMICI, the Italian IBD patients’ association, sent an anonymous web-based questionnaire in February 2021. Previous vaccination status and patients’ attitudes towards vaccinations were recorded. We examined the factors influencing their attitudes using crude and adjusted odds ratios (adjORs) with 95% confidence intervals (CIs). Results: Among the 4039 patients invited, 1252 patients (including 729 women, median age 47.7 [37–58]) completed the questionnaire, with a response rate of 25.3%. Respondents declared being vaccinated against tetanus (74.1%), flu (67.7%; last season), MMR (43.3%), HBV (37.1%), pneumococcus (29.1%), meningitis (20%), HAV (16%), VZV (15.3%), and HPV (7.6%). Complete vaccination history was not remembered by 20.7% of the patients. One thousand one hundred and twelve (88.8%) expressed a positive attitude towards vaccination, 91 (7.3%) were indifferent, and 49 (3.9%) reported being opposed to vaccinations. The belief of a possible return of VPDs with a decline in vaccination coverage rates was the factor most strongly related to a positive attitude towards vaccinations (adjOR 5.67, 95% CI 3.45–9.30, p-value < 0.001). Conclusions: A low vaccination rate against some VPDs was found among a national cohort of patients with IBD, despite a generally positive attitude towards vaccinations.

Bowel-associated arthritis–dermatosis syndrome (BADAS) is a rare neutrophilic dermatosis that was first described in 1971 in patients who underwent bypass surgery for obesity. Over the years, the number of reported cases associated with medical gastroenterological conditions, particularly inflammatory bowel disease (IBD), has progressively increased. To date, there are no systematic reviews in the literature on BADAS. The design of an a priori protocol was based on PRISMA guidelines, and a search of PubMed and Scopus databases was conducted for articles published between 1971 and 2023 related to the topic. Fifty-one articles including 113 patients with BADAS were analyzed in this systematic review. Bariatric surgery and IBD were the most frequently reported causes of BADAS, accounting for 63.7% and 24.7% of all cases, respectively. A total of 85% of cases displayed the typical dermatological presentation, including urticarial maculopapular lesions centered by a vesicopustule, with the majority of lesions located on the upper limbs (73.5%). Polyarthralgia or localized arthritis were always present. Atypical presentations included cellulitis-like, erythema-nodosum-like, Sweet-syndrome-like and pyoderma-gangrenosum-like manifestations. Gastrointestinal symptoms were frequently observed in IBD-related cases (67.9%). The histopathology showed a neutrophilic infiltrate (96.6%). The most commonly used treatment regimens consisted of systemic corticosteroids, metronidazole and tetracyclines, either alone or in combination. A relapsing–remitting course was observed in 52.1% of patients. In conclusion, BADAS is a neutrophilic dermatosis that presents with a wide variety of cutaneous manifestations, both typical and atypical. Gastrointestinal symptoms are frequently observed, particularly in cases related to IBD. The histopathology is clear but not specific compared with other neutrophilic dermatoses. The diagnosis can be challenging, but the relapsing–remitting course and the strong association with polyarthralgia and gastrointestinal disease can aid in the diagnosis.

ObjectivesUlcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis.DesignHBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo.ResultsHBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo.ConclusionThis study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

Abstract Background and Aim During the recent COVID-19 pandemic, telemedicine has enabled many IBD patients worldwide to get access to remote assistance. Some positive reports on the use of telemedicine among patients and healthcare providers have been published1-4, but a patient’s trust perspective is not available yet. The aim of our study was to verify IBD patients’ trust in telemedicine. This study was approved by our local Ethics Committee. Material and Methods At our Gastroenterology Unit in Milan (Italy), 123 video-consultations were delivered to IBD patients with mild or moderate disease, in place of follow-up visits scheduled but not provided during the general lockdown (March-April 2020). Video-calling solutions from Google (Hangouts or Meet) or Microsoft Teams were used according to the patient’s preference. The patients’ trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) questionnaire.5 The primary endpoint was expressed as a >75% percentage of patients giving a score of at least 4 out of 5 in a Likert Scale for three selected key statements: “I can trust video-consultation”, “I can trust that possible problems with the telemedicine service will be solved properly” and “I feel at ease when working with this website”. The questionnaire was formulated through the EUSurvey platform, widely used for clinical research questionnaires in Europe. Results One-hundred-fifteen (93.4%) video-consultations were performed out of the 123 scheduled. Among the 115 consultations, 100 questionnaires were completed (86.9%). The primary endpoint of trust in the telemedicine service was achieved in 95%, 90% and 84% of patients for the three selected key statements about the trust in the telemedicine service, its capability to solve clinical problems and its ease to use. While clinical outcomes were beyond our intentions, we reported no drugs withdrawal in this cohort nor major events. Conclusion Our results showed that during the COVID-19 pandemic most of our IBD patients accepted to receive a video-consultation in spite of the traditional in-person visit and trusted the video-consultation. References: 1. Bezzio C. et al. Gut 2020;69:1213–1217 2. George L.A., Raymond K. Current Gastroenterology Reports (2020) 22: 12 3. Lees C. W. et al. Gastroenterology 2020; 2020 May 28 4. Allocca M et al. Clin Gastroenterol Hepatol 2020;18:1882–1883 5. Velsen, L. V. et al, H. Int. J. Med. Inform 2017;97:52–58.

Background2.5 million people in Europe are diagnosed with IBD. IBD affects quality of life, but also has important consequences for health systems. It remains unknown if there are variations in IBD care across Europe and to help address this question, we conducted this European Variation In ibd PracticE suRvey (VIPER) to study potential differences.MethodsThis trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training and clinical care. The survey was distributed through social media and national GI societies from December 2020 - January 2021. Results were compared according to GDP per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank).ResultsThere were 1268 participants from 39 European countries. Most of the participants are specialists (65.3%), followed by fellows in training (>/< 3 years, 19.1%, 15.6%). Majority of the responders are working in academic institutions (50.4%), others in public/district hospitals (33.3%) or private practices (16.3%).Despite significant differences in access to IBD-specific training between high (56.4%) and low (38.5%) GDP countries (p<0.001) the majority of clinicians felt comfortable in treating IBD (77.2% vs 72.0%, p=0.04). Interestingly, a difference in availability of dedicated IBD units could be observed (58.5% vs 39.7%, p<0.001), as well as an inequality in multidisciplinary meetings (72.6% vs 40.2%, p<0.001), which often take place on a weekly basis (53.0%). In high GDP countries, IBD nurses are more common (86.2%) than in low GDP countries (36.0%, p<0.001), which is mirrored by differences in nurse-led IBD clinics (40.6% vs 13.8%, p<0.001). IBD dieticians (32.4% vs 16.6%) and psychologists (16.7% vs 7.5%) are mainly present in high GDP countries (p<0.001).On multivariate analysis (Abstract HMO1 Figure 1) GDP was not a factor that dictated confidence in treating patients with IBD. Those that had experienced specific IBD training were more than 3 times more likely to report confidence in treating IBD patients. Furthermore, there was a direct correlation with confidence related to the quantity of patients seen per week with each additional 10 patients improving confidence by a factor of 10. These factors are important as they are easily modifiable targets that can help improve confidence across Europe in managing patients with IBD.Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. Almost all (94.7%) use faecal calprotectin for routine monitoring, whereas half also use intestinal ultrasound (47.9%).Abstract HMO-1 Figure 1Factors associated with confidence on multivariate analysisConclusionA lot of variability in IBD practice exists across Europe, with marked differences between high vs low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardise IBD care across Europe.