Concomitant Inflammatory Bowel Disease Research Articles

DOP04 Single cell RNA sequencing identifies distinct intestinal inflammation patterns between primary sclerosing cholangitis-associated colitis and Ulcerative Colitis

Abstract Background Primary sclerosing cholangitis (PSC) is an inflammatory disorder of the bile ducts. The etiology of PSC is unknown, but it is hypothesized that intestinal barrier dysfunction, as seen in inflammatory bowel disease (IBD), plays a role. Roughly 75% of PSC patients have concomitant IBD (PSC-IBD). PSC-IBD is phenotypically different from ulcerative colitis (UC) with predominantly right-sided disease and a higher risk for colorectal cancer. In this study we aim aim to find probable distinct pathomechanisms for PSC-IBD, by comparing gut mucosal biopsies between PSC-IBD and UC using single-cell RNA sequencing. Methods 47 gut mucosal samples from the colon of subjects with either PSC-IBD (n=24), UC (n=18) or non-IBD control (n=5) were collected, from which 28 were paired inflamed and non-inflamed. Whole biopsies were cryopreserved and dissociated into single cells using collagenase digestion. Library preparation was done using the 10x Genomics system and subsequent sequencing was performed on an MGI2000 sequencer. The ‘Seurat’ R package was used for analysis. Results A total of 75.078 high quality cells identified 38 distinct cell types. No differences in cell type composition were observed between PSC-IBD and UC. We did see different cell type composition and gene expression between inflamed and non-inflamed samples. For example, in PSC-IBD specifically, an enterocyte subtype defined by DUOX2-expression showed inflammatory pathways upon inflammation. UC inflammation, on the other hand, was characterized by involvement of BEST4+ enterocytes and inflammatory fibroblasts. In addition, activated B cells and IgA plasma cells expressed stress-related genes in PSC, but not in UC inflammation. Conclusion We show that intestinal inflammation in PSC-IBD is characterized by distinct, cell-specific gene expression patterns as compared to UC. This highlights differential cell types mediating inflammation between these IBDs. Our study provides insight in cellular mechanisms underlying intestinal disease in PSC, and may serve as a starting point for further studies, for example on the functions of DUOX2+ enterocytes.

P360 Aggressive Inflammatory Bowel Disease is associated to Hermansky-Pudlak Syndrome: Characterization of a Puerto Rican Cohort

Abstract Background Hermansky-Pudlak Syndrome (HPS), a rare autosomal recessive disorder, is the most common single-gene disorder in Puerto Rico. It is characterized by an aberrant biogenesis of lysosome-related organelles inducing oculocutaneous albinism, bleeding diathesis, and damage to other organs. Around 30% of patients with HPS develop granulomatous enterocolitis, a Crohn’s-like inflammatory bowel disease (IBD). The mutant HPS1 gene is associated with a more severe Early Onset IBD (EO-IBD). We wish to describe a group of patients with HPS-associated IBD. Methods Puerto Ricans with HPS and concomitant IBD were recruited in our IBD clinic for a prospective cohort study. After informed consent, demographic and medical data were collected from the patient and the medical record. Variables included sex, HPS genotype, age at the time of IBD diagnosis, IBD location and behavior according to Montreal and Paris Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). Descriptive analysis was performed calculating mean and standard deviations. This study is approved by the MSC IRB. Results 13 patients with HPS and IBD, 9 with confirmed genotype 1, were identified: 8 males and 5 females. The mean age at the time of IBD diagnosis was 22 ± 11 years. 6 were diagnosed at ≤ 16 y/o (A1), 6 were diagnosed between 17-40 years (A2) and 1 patient was in the range of EO-IBD (7 y/o). 9 patients had advanced penetrating behavior (B3) of which 7 had concomitant perianal involvement. Most patients (9) had a surgical intervention; 8 have an ostomy. The majority (10) are using biologics (4 with concurrent immunomodulators). The most frequent EIM was peripheral arthropathy seen in 45%. Conclusion HPS patients had a severe course of IBD, as shown by age at diagnosis, phenotype, the prevalence of perianal disease, surgery and use of biologics. In comparison to a database of 836 Puerto Ricans with non HPS Crohn’s Disease, those with HPS were more likely to have surgeries (69% vs 55%, P=.303) and use biologics (77% vs 43%, P=.015). Gastrointestinal symptoms including bleeding may be overlooked by the primary physician. Proactive vigilance in patients with HPS to make an early diagnosis of IBD and aggressive medical treatment may result in better outcomes for these patients.

P124 Gastroenteropancreatic Neuroendocrine Neoplasms in patients with Inflammatory Bowel Disease: An ECCO CONFER Multicentre Case Series

Abstract Background Neuroendocrine Neoplasms (NENs) are a heterogeneous group of tumours deriving from the diffuse endocrine system. NENs may occur almost everywhere in the body but are most common in the gastrointestinal tract, the pancreas, and the lungs, with gastroenteropancreatic (GEP) tumours representing 70% of all NENs. GEP-NENs have rarely been reported in association with inflammatory bowel diseases (IBDs) but no definitive relationship between these tumours and IBD has been established Methods This was an ECCO COllaborative Network For Exceptionally Rare case reports project (ECCO-CONFER). We included cases of GEP-NENs diagnosed in patients with IBD that met the diagnostic criteria for NEN according to the European Neuroendocrine Tumour Society. Data were retrospectively collected in a standardized case report form and analysed for event association with patient’s and IBD-related factors Results GEP-NEN was diagnosed in 100 patients with IBD [61% female, 55% Crohn’s disease, median age 48 years (IQR 37–59)]. Overall the most common location was the appendix (39/100) followed by the colon (22/100). Complete IBD-related data was available for 50 individuals with a median follow-up of 30.5 months (IQR 11.2–70) following NEN diagnosis. At the last follow-up data, 47/50 patients were alive. Three deaths occurred, of which 2 were related to NEN. Median duration of IBD at NEN diagnosis was 84 months (IQR 10–151), and in 18% of cases NEN and IBD were diagnosed concomitantly. 20/50 of NENs were at stage I (T1N0M0) and 28/50 graded G1 (ki 67 ≤2 %) at diagnosis. Incidental diagnosis of NEN either during follow-up or during surgery as well as receiving diagnosis of NEN concomitantly with IBD was significantly associated with an earlier NEN stage (p< 0.01 and p<0.02, respectively). Exposure to immunomodulatory and/or biologic therapy was not associated with advanced NEN stage or grade. Interestingly, primary GEP-NEN sites significantly correlated to the segment affected by IBD (62% vs 38% p = 0.02) Conclusion In the largest case series to date, prognosis of patients with concomitant GEP-NEN and IBD seems favorable. Incidental NEN diagnosis correlates with an earlier NEN stage and IBD-related therapies are independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

The Clinical Characteristics and Treatment Outcomes of Concomitant Eosinophilic Esophagitis and Inflammatory Bowel Disease.

The clinical characteristics and treatment outcomes in patients with eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have not been extensively investigated. We determined treatment outcomes and frequencies of disease-related complications in patients with EoE and IBD. Among 69 patients who met inclusion criteria, 39 (56.5%) had a diagnosis of Crohn disease. Clinical and histologic response rates to proton pump inhibitors and topical steroids were 25.9% and 24.4%, respectively. Lower than expected clinical and histologic response rates for EoE suggest the combination of EoE and IBD is a medically refractory phenotype with more difficult to treat EoE.

95332 Intestinal inflammation and altered gut microbiota associated with inflammatory bowel disease render mice susceptible to Clostridioides difficile colonization and infection

ABSTRACT IMPACT: Use of this novel murine model of inflammatory bowel disease (IBD) and C. difficile infection (CDI) will aid in developing new clinical approaches to predict, diagnose, and treat CDI in the IBD population. OBJECTIVES/GOALS: IBD is associated with intestinal inflammation and alterations of the gut microbiota, both of which can diminish colonization resistance to C. difficile. Here, we sought to determine if IBD is sufficient to render mice susceptible to C. difficile colonization and infection in the absence of other perturbations, such as antibiotic treatment. METHODS/STUDY POPULATION: C57BL/6 IL-10-/- mice were colonized with Helicobacter hepaticus to trigger colonic inflammation akin to human IBD. Control mice, not colonized with H. hepaticus, were pretreated with the antibiotic cefoperazone to render the gut microbiota susceptible to CDI. Mice were then gavaged with spores of the toxigenic C. difficile strain VPI 10463 and monitored for C. difficile colonization and disease. The fecal microbiota at the time of C. difficile exposure was profiled by 16S rRNA gene sequencing and analyzed using mothur. Statistical analyses were performed using R. RESULTS/ANTICIPATED RESULTS: Mice with IBD harbored significantly distinct intestinal microbial communities compared to non-IBD controls at the time of C. difficile spore exposure (14 days post-IBD trigger). Mice with IBD were susceptible to persistent C. difficile colonization, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse clinical and intestinal disease than unaccompanied IBD. DISCUSSION/SIGNIFICANCE OF FINDINGS: Patients with IBD who develop concurrent CDI experience increased morbidity and mortality. These studies in a novel mouse model of IBD and CDI emphasize the dual importance of host responses and alterations of the gut microbiota in susceptibility to C. difficile colonization and infection in the setting of IBD.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Trends of Liver Stiffness in Inflammatory Bowel Disease with Chronic Hepatitis C.

Concomitant inflammatory bowel disease (IBD) and hepatitis C virus (HCV) infection is a relevant comorbidity since IBD itself exposes to a high risk of liver damage. We aimed to evaluate liver stiffness (LS) in IBD-HCV after antiviral treatment. We enrolled IBD patients with HCV. All patients at baseline underwent LS measurement by elastography. Patients who were eligible for antiviral therapy received direct antiviral agents (DAAs) and sustained viral response was evaluated at the 12th week. A control group was selected within IBD patients without HCV. One year later, all IBD-HCV patients and controls repeated LS measurement. Twenty-four IBD-HCV patients and 24 IBD controls entered the study. Only twelve out of 24 received DAAs and all achieved sustained viral response (SVR). All IBD subjects were in remission at enrollment and maintained remission for one year. After one year, IBD patients who eradicated HCV passed from a liver stiffness of 8.5 ± 6.2 kPa to 7.1 ± 3.9, p = 0.13. IBD patients who did not eradicate HCV worsened liver stiffness: from 7.6 ± 4.4 to 8.6 ± 4.6, p = 0.01. In the IBD control group, stiffness decreased from 7.8 ± 4.4 to 6.0 ± 3.1, p < 0.001. In conclusion, HCV eradication is able to stop the evolution of liver fibrosis in IBD, while failure to treat may lead to its progression. A stable IBD remission may improve LS even in non-infected subjects.

15099 Association of psoriasis with inflammatory bowel disease: A retrospective study

Psoriasis is a chronic inflammatory disease characterized by localized or widespread silvery, scaly, and erythematous plaques distributed symmetrically. Several studies have demonstrated the association of psoriasis with inflammatory bowel disease (IBD). IBD comprises two principle phenotypes, Crohn disease (CD) and ulcerative colitis (UC). The prevalence and relative risk of IBD in psoriatic patients and in those with psoriatic arthritis (PsA) are higher than in the general population. This study aims to determine IBD prevalence in patients with psoriasis while correlating IBD with psoriasis phenotype. A retrospective cohort study was performed reviewing charts at the University of Puerto Rico Dermatology Clinics from January 2016 to March 2019. The following were assessed: demographics, past medical history, age at IBD diagnosis, treatment, and PsA. Total number of patients with psoriasis was 719 of which 9 (1.12%) had IBD with a mean age at diagnosis of thirty; 33% (3) had Crohn disease, and 67% (6) had ulcerative colitis. PsA was observed in 33% of patients with concomitant IBD and psoriasis. Prevalence of PsA, rheumatoid arthritis, diabetes mellitus, and hypercholesterolemia did not differ between IBD and non-IBD groups. Our study showed that 67% of patients who developed IBD presented with mild psoriasis, whereas 62% of patients with psoriasis without IBD presented with severe psoriasis. Biologic treatment for psoriasis correlated with fewer IBD symptoms. Our study compares to other studies and makes us consider implementing biologic treatment for psoriasis earlier in the course to prevent other inflammatory diseases such as IBD.

S3215 Hermansky-Pudlak-Associated IBD: Is It the Same? Description of a Puerto Rican Cohort

INTRODUCTION: Hermansky-Pudlak Syndrome (HPS) is the most common single gene disorder in Puerto Rico. It is a rare autosomal recessive disorder due to aberrant biogenesis of lysosome-related organelles leading to oculocutaneous albinism, bleeding diathesis, and involvement in other organs. About 30% of patients with HPS develop a form of Crohn’s-like inflammatory bowel disease (IBD), granulomatous enterocolitis. Whether this is a manifestation of HPS or true IBD is still in debate. We wish to describe a group of patients with HPS-associated IBD. METHODS: This is a prospective cohort study in which phenotypically identified patients with HPS and concomitant IBD are recruited. After informed consent, a questionnaire with demographic and medical data is administered through patient interview and record review is performed. The variables collected are sex, HPS genotype, age at the time of IBD diagnosis, comorbidities, IBD location and behavior according to Montreal Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). This study is approved by the IRB. RESULTS: Ten patients with HPS and concomitant IBD were identified in our clinics - 5 males and 5 females. HPS genotype in 9 showed 8 were HPS-1 and 1 was HPS-3. The mean age at the time of IBD diagnosis was 22 ± 10 years. Six were diagnosed between ages 17 and 40 years and 4 patients were diagnosed at ≤16 y/o. Seven patients had colonic involvement, 3 had ileocolonic involvement. Sixty percent of patients had an advanced penetrating behavior and 50% had perianal involvement. Six patients had some type of surgical intervention. Three patients were on both a biologic and an immunomodulator (IMM), 5 were on a biologic alone, 1 on IMM alone, and 1 without maintenance treatment. The most frequent EIM was anemia in 40% of patients. CONCLUSION: HPS patients had a severe course of IBD, as shown by phenotype, surgery, and use of biologics. A younger age at diagnosis and a higher than usual prevalence of perianal disease also predict a complicated course. Further studies are necessary to determine if HPS-associated IBD is related to the genetic defect and if this may result in a different clinical course than idiopathic IBD.

S1574 Colorectal Cancer in a Young Male With Primary Sclerosing Cholangitis Without Underlying Inflammatory Bowel Disease

INTRODUCTION: Primary Sclerosing Cholangitis (PSC) presents with hepatic duct inflammation, fibrosis and stricturing leading to biliary obstruction, recurrent cholangitis and eventually end-stage liver disease. There is a strong association between PSC and Inflammatory Bowel Disease (IBD), especially Ulcerative Colitis (UC), which itself is strongly associated with Colorectal Cancer (CRC) development. Thus, all patients diagnosed with PSC must undergo a colonoscopy to evaluate for concomitant IBD even if asymptomatic at the time of diagnosis. The cumulative absolute risk of CRC or dysplasia in patients with both PSC and UC is approximately 5 to 6 times higher than CRC in UC alone. The classic presentation of PSC is marked by abnormal liver enzymes or cholestatic symptoms. Subsequent colonoscopy identifies underlying IBD in up to 80% of cases which often progresses to CRC. We describe the case of a healthy 29-year-old male newly diagnosed with PSC. Colonoscopy revealed an extremely rare presentation of adenocarcinoma without apparent underlying IBD. CASE DESCRIPTION/METHODS: 29-year-old active-duty male presented with 6 days of nausea, vomiting, scleral icterus and abdominal discomfort. Initial total bilirubin was 11.7 mg/dL with transaminitis, elevated alkaline phosphatase and CA 19-9. IBD panel and infectious workup were negative. RUQUS and abdominal CT revealed segmental dilatation of common bile duct and mural thickening of the sigmoid colon. Follow-up MRCP / ERCP showed severely stenotic main bile duct limiting further evaluation (Figure 1). Colonoscopy found a hemicircumferential, ulcerated, friable 4 cm × 3 cm mass in the sigmoid colon, with otherwise normal colonic mucosa (Figure 2). Histologic examination demonstrated invasive poorly differentiated adenocarcinoma. His bilirubin continued to rise to 19.4 mg/dL and required biliary drain placement. Subsequent CT chest showed multiple scattered, solid nodules and the patient was transferred for further staging and potential liver transplant. DISCUSSION: This case is notable as our patient’s PSC diagnosis was immediately followed by the discovery of colon adenocarcinoma without underlying IBD. Though IBD in patients with PSC tends to be asymptomatic at the time of diagnosis, the endoscopic and histologic appearance of the colon is nearly always consistent with underlying IBD. This case exemplifies that PSC may be a direct risk factor for the development of CRC even in the absence of underlying IBD.Figure 1.: ERCP with limited contrast transmission (arrow) due to the severely stenosed main bile duct.Figure 2.: Fungating Sigmoid Colon lesion prior to biopsy.

Alterations of the salivary and fecal microbiome in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease known for its frequent concurrence with inflammatory bowel disease. PSC can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. The etiopathogenesis of PSC remains poorly understood, and, as such, pharmacotherapy has yet to be definitively established. Little is known about the salivary microbiome in PSC and PSC-IBD. This study aimed to evaluate the oral microbiome of patients with PSC, with association to these patient's fecal microbial composition. Saliva, fecal samples and Food Frequency Questionnaires were collected from 35 PSC patients with or without concomitant inflammatory bowel disease and 30 age- and BMI-matched healthy volunteers. 16S rRNA gene sequencing was performed using Illumina MiSeq platform. The salivary microbial signature of PSC was significantly altered as compared to healthy controls, independent of concomitant IBD, and was comprised of 19 significantly altered species, of which, eight species were consistently overrepresented in both fecal and saliva of patients with PSC, including Veillonella, Scardovia and Streptococcus. PSC is characterized by microbial dysbiosis in the gut and the salivary microbiome, independently from IBD. The PSC dysbiotic signature includes a reduction in autochthonous bacteria and an increased relative abundance of pathogenic bacteria, including an invasion of oral bacteria to the gut. PSC is a strong modulator of the microbial profile, in the gut and the oral microbiome. These results may lead to the development of biomarkers for screening and early diagnosis or the development of personalized medicine in PSC.

Treatment of Juvenile Spondyloarthritis: Where We Stand

Juvenile spondyloarthritis is a subset of juvenile idiopathic arthritis (JIA) with onset in late childhood and adolescence and a strong association with human leukocyte antigen (HLA) B-27 positivity and familial aggregation that has the potential for axial involvement, potentially leading to ankylosing spondylitis. Current therapy for severe disease relies heavily on tumor necrosis factor inhibitors (TNFi). Treatment paradigms in children largely consist of extrapolation from studies on adults with spondyloarthritis. Additional therapies studied in adults include non-steroidal anti-inflammatory drugs (NSAIDs), blockade of the interleukin-17 (IL-17) and IL-23 axes, blockade of T-cell stimulation, phosphodiesterase (PDE)-4 inhibition, and Janus-activated kinase (JAK) pathway alteration. IL-17 blockade and IL-23 blockade are guideline approved after TNFi failure (and even as an alternative to TNFi) in adults, depending on concomitant inflammatory bowel and skin disease, with JAK and PDE-4 inhibition options following biologic failure. Neither pediatric nor adult guidelines address IL-6 blockade, T-cell co-stimulation blockade, or combination biologic therapy.

LIVER TRANSPLANTATION FOR PRIMARY SCLEROSING CHOLANGITIS

Introduction: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin. Liver transplantation (LT) is require in more than half of this patients. In this study, we analyzed our results in the patients with LT owing to PSC. Materials and Methods: A total of 649 LT were performed in our center between December 1988 and December 2019. The results were retrospectively analyzed from 12 patients, who underwent LT for PSC. Demographic features, presence of any concomitant inflammatory bowel disease (IBD), time to LT, and outcome data were recorded. Results: There were 12 patients (8 men and 4 women). Ten of the patients were adult and 2 of them were pediatric patient. Mean age of these patients was 27 ± 12 (range, 5 to 40 years). Seven of the transplantations were living donor liver transplantation. Mean follow-up period was 123±49 months. Bile duct reconstruction was performed with hepaticojejunostomy in 7 patients and duct to duct in 5 patients. Biliary leakage was detected in 4 patients postoperatively and they were treated with interventional radiological techniques successfully. Biliary stenosis developed in 4 patients in the late period and 3 of them were treated with interventional radiological methods. In 1 patient surgical treatment was applied. In 1 patient PSC recurred 11 years after LT and retransplantation was performed. Two patients passed away during the follow up period due to sepsis. Conclusions: LT in PSC resulted in favorable outcomes regarding postoperative morbidity and mortality compared with other etiologies.

Long-term oral vancomycin for refractory inflammatory bowel diseases without Clostridium difficile infection: Lessons from primary sclerosing cholangitis

Dysbiosis is a prominent feature of inflammatory bowel diseases (IBD). However, the efficacy of using antibiotics aiming at the aberrant gut microflora for IBD treatment are either unsuccessful or not persistent. In contrast, long-term oral vancomycin has been proved effective in controlling both the bile duct and gut inflammation of primary sclerosing cholangitis (PSC), an autoimmune disease against the intra- and extrahepatic bile ducts that holds a high rate of concomitant IBD and shares many common characteristics with IBD, including similar dysbiosis patterns. Two discrepancies of antibiotic usage might explain the dramatically different responses of the two diseases toward this strategy. First, the vast majority of antibiotic formulas for IBD management consist of broad-spectrum antibiotics mainly targeting gram-negative bacteria with some covering anaerobes and gram-positive ones, while vancomycin used for PSC treatment almost exclusively targets gram-positive bacteria. Several lines of clues suggested that gram-positive microorganisms might be responsible for the chronic inflammation observed in IBD and PSC. Second, improvement of liver test in PSC patients is usually observed after a relatively long period of oral vancomycin treatment (more than 12 weeks) and it takes even longer for gut mucosal healing. Moreover, long-term low dose oral vancomycin is required to prevent PSC recurrence. However, most trials of using antibiotics for IBD management is aiming at inducing remission with short treatment course (most less than 2 weeks) without maintenance. We hypothesize that the host antimicrobial response favors the growth of certain gram-positive intestinal bacteria in genetically predisposed individuals which is responsible for the aberrant immunological reaction towards the gut mucosa. Oral vancomycin induces disease remission by suppressing the pathogenic gram-positive microorganisms, but long course is needed since the gut inflammation is usually severe than that concomitant with PSC. Moreover, long-term maintenance is required to prevent the rebound of the pathogens and flare of the intestinal inflammation.

Autoimmune pancreatitis type 2.

Type 2 autoimmune pancreatitis (AIP) is a rare inflammatory disease of the pancreas. Very few data have been published on this particular subtype, which differs from the 'classical' IgG4-related type 1 AIP in terms of pathological features, epidemiology and risk of relapse. The aim of the current review is to summarize the available literature, suggesting a diagnostic and therapeutic approach to this disease. Based on the International Consensus Diagnostic Criteria, to achieve a 'definitive' diagnosis of type 2 AIP, histology is required. If a definitive histological diagnosis is lacking (not-performed or inconclusive), concomitant presence of inflammatory bowel disease (IBD) and effective response to steroids are needed for a 'probable' diagnosis of type 2 AIP. Type 2 AIP is a selective pancreatic disease, without association to other organ involvement. The lack of validated serological markers makes the diagnosis challenging in clinical practice, particularly in focal forms. A careful evaluation of the clinical profile (especially of a concomitant IBD), associated with an accurate imaging, might help in clinical practice to suspect type 2 AIP. Response to steroids is crucial to achieve diagnosis in patients without a diagnostic histology.

THU0340 DURATION AND SYSTEMIC SCLEROSIS SUBTYPE ARE ASSOCIATED WITH DIFFERENT GUT MICROBIOME PROFILES

Background:A growing body of evidence suggests that the gut microbiota plays a significant role in the development of autoimmune diseases. Altered microbiota composition was associated with gastrointestinal and extraintestinal features in systemic sclerosis (SSc) patients.Objectives:To look for differences in gut microbiota between SSc patients regarding disease duration, disease subset and occurrence of digital ulcers (DU).Methods:SSc patients seen at our center were recruited in a prospective study. The exclusion criteria included antibiotic or probiotic treatment during the month prior to recruitment, recent hospitalization, BMI&gt;30, diabetes mellitus or concomitant inflammatory bowel disease. Fecal samples were processed and 16S rRNA gene sequences were analyzed using the QIIME2 packageWeighted (quantitative) and unweighted (qualitative) UniFrac distances, alpha diversity for richness and homogeneity, taxa plots for species and phyla and ANCOM analyses were performed.Results:During July 2018-May 2019, 26 SSc patients (mean age [SD] 53[12.7] years) and disease duration 8.8 [7.1] years) fulfilled the criteria and were willing to participate in the study. Thirteen patients had diffuse SSc, 16 patients had active DU, 8 patients had Raynaud’s phenomenon only without DU, 2 patients had past DU. The microbiota was significantly more similar between patients without active DU compared to those with active DU (P=0.024), but species richness did not differ. Patients with SSc duration less than 6 years had significantly different microbiota compared to long-lasting SSc (unweighted PCoA – q=0.031). Significant variations concerning quantitative and qualitative UniFrac distances (q=0.063, q=0.005) and species richness (q=0.009) were found among patients with diffuse compared to limited SSc. Limited SSc was associated with greater species richness. Taxa plot analysis revealed higher relative abundance of Firmicutes in diffuse disease and of Actinobacteria and Bacteroidetes in limited SSc.Conclusion:Disease duration, disease subset and active DU were associated with shifts in the microbiome of SSc patients. The impact of these changes on disease progression needs further elucidation.Figure:Disclosure of Interests:Yolanda Braun-Moscovici: None declared, Shira Ben Simon: None declared, Katya Dolnikov: None declared, Sami Giryes: None declared, Doron Markovits: None declared, Yonit Tavor: None declared, Kohava Toledano: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Omry Koren: None declared

P401 Sarcopenia in children and young adults with primary sclerosing cholangitis and IBD

Abstract Background Malnutrition is common in children with inflammatory bowel disease (IBD) and in liver diseases. The nutritional status can be assessed by evaluating for sarcopenia, which is described as the loss of muscle mass and/or strength that are reflected by decreased psoas muscle surface area (PMSA). Accumulating data shows association of PSMA with chronic diseases, however, literature regarding sarcopenia in children is still limited. The aim of this study is to assess sarcopenia in children and young adults with sclerosing cholangitis (PSC) with or without IBD. Methods Retrospective analysis of patients below 25 years of age diagnosed with PSC between the years 2010–2018 was done. Patients who performed magnetic resonance imaging (MRI) were included in the study. Detailed clinical, anthropometric, laboratory and imaging findings were recorded. The control group was comprised of children who underwent MRI due to suspected scoliosis or kidney structural anomalies and had normal study. PMSA was determined at intervertebral disc L3. Results Sixty-five patients were included in the study. Twenty with PSC with a mean age of 15.2 ± 5 years, 12 were female and 9 had IBD. The control group comprised of 45 healthy subjects with no significant difference in age, gender and BMI from the study group. There was no significant difference in PMSA between groups. However, PMSA significantly correlated with aspartate transaminase (AST) and Platelet Ratio Index (APRI) score (marker for hepatic fibrosis, r = −0.49, p = 0.02). Additionally, PMSA was significantly higher in patients who had both PSC and IBD (475.61 ± 136 vs. 789 ± 328, p = 0.01). Conclusion Children and young adults with concomitant PSC and IBD were in a better nutritional status in comparison to patients with PSC alone, as evidenced by a lesser degree of sarcopenia. Additionally, sarcopenia correlates to the degree of liver fibrosis assessed by APRI score. Further larger studies are warranted in order to corroborate the importance of sarcopenia in patients with PSC.

P231 Epidemiological profile and long-term outcomes from a large PSC-IBD cohort

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic disease associated with inflammatory bowel diseases (IBD) in 70% of cases.1 When combined, they present as one distinct phenotypical disease referred to as PSC-IBD with milder clinical course, despite more extensive colonic involvement and an increased risk of malignancies. The aim of this study was to assess clinical features and long-term outcomes of PSC-IBD patients from a quaternary hospital in Brazil. Methods We retrospectively reviewed all PSC-IBD patients registered and followed-up in our outpatient clinic between January 2000 and July 2019. Conventional colonoscopic and histological criteria were used to diagnose IBD, whereas radiographic or histological criteria for PSC. Medical records were abstracted for the following data: demographic characteristics; duration, extent, and treatment of IBD; duration, extent, and treatment of PSC; colorectal neoplasia (dysplasia and cancer); surgical treatment for IBD; liver transplantation and death. Results In total, 92 patients with concurrent PSC and IBD were identified. Of 92 cases, 80 (87%) had ulcerative colitis (UC) and 12 (13%) were diagnosed with Crohn’s disease (CD). There was a slight predominance of male, 51 (55%). The mean age at both IBD and PSC diagnosis was 31 and 35 years, respectively. Most of them were diagnosed with IBD prior to PSC (53%). The mean IBD duration was 15 years and 10 years in PSC subjects. The prevalence of pancolitis in UC patients was 91%. All CD cases presented ileocolonic involvement. Present or past smoking history was reported in 6% of the cohort. Aminosalicylates were the most common treatment used for IBD in 59 patients (64%). 15 of them (16%) were on monotherapy with immunobiologics and 7 patients (8%) were on combotherapy. Only 3 subjects were on anti-integrin. In our cohort, 61 cases (66%) were treated with ursodeoxycholic acid. Colorectal neoplasia and cholangiocarcinoma were observed in 6 (7%) and 3 patients (3.3%), respectively. Colorectal dysplasia was found in 20 subjects (22%) on a routine colonoscopy. Overall, 17 patients (19%) required proctocolectomy and 11 cases (12%) have undergone orthotopic liver transplant. There were 12 deaths, mainly PSC and cancer-related. Conclusion Herein we present the largest cohort of concomitant PSC and IBD in Latin America. In our centre, we have found higher rates of extensive IBD, although few of them required colectomy. The present data on cancer and dysplasia are consistent with reports in the literature. Reference

P747 Adherence to ECCO guidelines for cancer surveillance is associated to the detection of early cancer: A retrospective, single-centre, cohort study

Abstract Background Patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) are at increased risk of developing gastrointestinal (GI) malignancies. The aim of this study is to assess the risk of malignancies in IBD patients and the impact of cancer screening according to the ECCO guidelines in a tertiary referral centre. Methods We retrospectively analysed the electronic database of all IBD patients followed by the IBD Centre of Humanitas Research Hospital, Milan, from January 2010 to October 2019, and collected all new diagnoses of solid and haematological tumours since 2010. The annual standardised incidence rate (SIR), rate of mortality and early cancer diagnosis were calculated and a descriptive analysis of drug exposure, disease duration, family history of any cancer, smoking habits was made. Results We included 5239 patients, with a total 19820 patient-years follow-up. Eighty-four malignancies in 81 patients were retrieved, 71 were included in the final analysis (38 CD, 32 UC, 31 females). Average age at tumour diagnosis was 52.9 years (range 19–78). 64% of patients were former or active smokers, 31% had a family history of cancer or IBD. Sixty-two per cent of patients were previously exposed or had 5-ASA at the time of cancer, 40% azathioprine, 43% anti-TNF or vedolizumab. The annual SIR for all kinds of malignancy was 0.358%. GI malignancies were the most frequent (n = 17, 23.9%, 47% UC, 53% in CD). Six over 8 GI tract malignancies in UC patients were found in the colon or rectum (mean disease duration 22.5 years), whereas in CD patients 5/9 were in the small-bowel (mean disease duration 7.0 years). Melanoma and breast cancer (n = 8 each) were the most common non-GI cancers, followed by prostate (n = 7) and bladder (n = 6). No significant difference in incidence was found between CD or UC. Non-Hodgkin lymphomas and leukaemia (3 and 1, respectively) only occurred in CD patients. Other tumours included thyroid (n = 5), lungs (n = 4), testicle (n = 3), ovary (n = 2), kidney (n = 2), head-nose-throat (n = 2), pancreas (n = 1), brain (n = 1), and non-melanoma skin cancer (n = 1). Death occurred in 11% of patients, 8 of them for late stage cancer. Only 2 were related to the concomitant IBD (1 colo-rectal and 1 anal cancer). In patients regularly screened according to the ECCO Guidelines (GI cancer, haematological and skin cancer), there was a significantly higher number of detection of early cancer (28 vs. 1, p = 0.003), although no differences in mortality rates were reported in the two groups (2 vs. 2, p = 0.10). Conclusion The overall incidence of cancer in our cohort was not different from the current literature available. Adherence to the ECCO Guidelines for cancer surveillance improves the detection of early cancer in IBD patients.