Complications In Inflammatory Bowel Disease Patients Research Articles

P1108 Factors Associated with Delayed Diagnosis of Inflammatory Bowel Disease and Risk of Complications: Analysis of the Brazilian National Registry

Abstract Background The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) has established a national registry of inflammatory bowel disease (IBD). Timely diagnosis and treatment of the disease are crucial to mitigate the risk of complications in this patient population. Therefore, this study aimed to assess the variables associated with delayed diagnosis and the frequency of complications in IBD patients in Brazil. Methods A cohort study was conducted from August 2020 to August 2023. Data were obtained from medical records and patient consultations using the REDCap platform, with approvals from the ethics boards of participating institutions. Patients were categorized based on the time from symptom onset to diagnosis: < 1 year, 1 to 1 year 11 months, and ≥ 2 years. Socioeconomic and clinical data, such as disease extension, use of biological therapy, and complications like the need for surgery or hospitalization, were evaluated. Results The study included 2,436 patients, with 1,147 diagnosed with ulcerative colitis (UC) and 1,289 with Crohn's disease (CD). Of these, 62% were managed in public centers, and 38% in the private system. The age at diagnosis was 38 ± 15.5 years for UC and 33.7 ± 14.9 years for CD, with females predominating (64.5% for UC and 53.4% for CD). Among UC patients, disease extension included pancolitis (43.5%), left colitis (28.8%), and proctitis (27.7%). The time between symptom onset and diagnosis was longer in CD patients (p<0.001), as follows: < 1 year (UC 58.4% and CD 50.9%), 1 to 1 year 11 months (UC 22.3% and CD 21.1%), and ≥ 2 years (UC 19.3% and CD 28%). The shortest interval in UC patients was observed in private services (p<0.001), Southern and Northeastern regions of Brazil (p<0.001), and in patients without extraintestinal manifestations (EIM) (p=0.003). No differences were noted regarding disease extent, need for surgery, hospitalization, presence of cancer, or use of biological therapy. In CD patients, the shortest interval was observed in private services (p<0.001), the Southern region of Brazil (p<0.001), and was associated with a lower rate of hospitalization due to complications or disease activity (p=0.032). Among those who underwent surgery (35.6%), patients operated on in a public university hospital experienced a greater delay in diagnosis (p=0.014). No differences were observed regarding the presence of perianal disease, need for surgery, cancer, or use of biological therapy. Conclusion The window of opportunity is imperative to reduce complications, especially in CD. Further epidemiological studies are needed to shape national public health policies, emphasizing early diagnosis and appropriate treatment of IBD.

A MEDICAL AND NEUROPSYCHIATRIC MANAGEMENT SURVEY IN A BRAZILIAN COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD).

Inflammatory bowel disease (IBD) can be accompanied by several neurological disorders. Since 2004, we started a Brazilian cohort to assess neuropsychiatric complications in IBD patients. Changes in therapeutic strategy and differences in the prevalence and relevance of neuropsychiatric disorders have been reported in the literature. We conducted a short patient-reported survey about the medical management of IBD (with a special focus on neuropsychiatric management) and its complications. During the enrollment period (9/1/2021 to 8/31/2022), 279 patients with IBD answered the survey (128 patients with ulcerative colitis and 151 with Crohn's disease). This is the first medical management survey aimed to verify the level of perception of IBD patients about their neuropsychiatric conditions. We found a high prevalence of neurologic (59%), psychiatric (32%), and neuropsychiatric co-morbidities (69%). There is a marked discrepancy between the findings of neurological disorders reported in our studies over the first 10 years of the cohort in comparison with the current perception/knowledge among the patients registered in the present management survey. Patients tend to have a better understanding of central rather than peripheral nerve conditions. • What is already known? • The prevalence and spectrum of neuropsychiatric co-morbidities varies among different epidemiologic studies. • What is new here? • Patients self report a high percentage of neuropsychiatric diseases but tend to better recognize central rather than peripheral nervous system disorders. • How can this study help patient care? • This study may guide practioners to educate IBD patients about their neuropsychiatric co-morbidities.

Thrombotic Complications in Inflammatory Bowel Disease: The Role of Coagulation Markers and Family History

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized mainly by intestinal pathology. The risk of thrombosis increases in IBD patients, increasing overall disease morbidity and mortality. We aim to investigate the role of coagulation markers in determining the risk of thrombotic complications in IBD patients compared to healthy controls. Methods: The study was approved by the institutional review board. All patients aged 16 or over, diagnosed with IBD and followed at our center from January 2012 -2022, were included. We investigated the family history and the hemostatic profiles of these patients. Descriptive statistics were computed for continuous variables, including means, standard deviations (SDs), minimum and maximum values, as well as 95% confidence intervals (CIs), where appropriate, and frequencies for categorical variables. Fisher exact test was used for categorical variables. Student t-test was used for continuous variables. Results: A total of 100 patients were included in the study, comprising of 51 (24%) females and 158 (76%) males. 73% of patients were diagnosed with Crohn's disease (CD), and 27% with ulcerative colitis (UC). Deep vein thrombosis (DVT) was observed in 5 (2.3%) of patients. In patients with a family history of DVT, 1.9% had developed a thrombotic event. Among continuous variables, prothrombin time, thrombin clotting time, and fibrinogen levels had mean values significantly different for patients with thrombosis than those without thrombosis ( p-values 0.01, 0.01, and 0.03, respectively). Conclusions: Patients with both UC and CD are at an increased risk of thrombosis. A family history of IBD can increase the risk of these events. The coagulation markers, including PT, TTC, and fibrinogen levels, can be used as biomarkers to predict the risk of thrombosis and the evaluation of the hemostatic profiles of IBD patients regularly, which can help prevent serious thrombotic complications and thus reduce morbidity and mortality resulting from these events. Therefore, such evaluation should be included in the routine examination protocols of high-risk IBD patients. This study may help better understand the biology of disease.

Splanchnic Vein Thrombosis in Inflammatory Bowel Disease: An Observational Study from the ENEIDA Registry and Systematic Review

Background: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD. Aims: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series. Methods: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients. Results: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn’s disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients. Conclusions: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.

Risk assessment of venous thromboembolism in inflammatory bowel disease by inherited risk in a population-based incident cohort.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the digestive tract with increasing prevalence globally. Although venous thromboembolism (VTE) is a major complication in IBD patients, it is often underappreciated with limited tools for risk stratification. To estimate the proportion of VTE among IBD patients and assess genetic risk factors (monogenic and polygenic) for VTE. Incident VTE was followed for 8465 IBD patients in the UK Biobank (UKB). The associations of VTE with F5 factor V leiden (FVL) mutation, F2 G20210A prothrombin gene mutation (PGM), and polygenic score (PGS003332) were tested using Cox hazards regression analysis, adjusting for age at IBD diagnosis, gender, and genetic background (top 10 principal components). The performance of genetic risk factors for discriminating VTE diagnosis was estimated using the area under the receiver operating characteristic curve (AUC). The overall proportion of incident VTE was 4.70% in IBD patients and was similar for CD (4.46%), UC (4.49%), and unclassified (6.42%), and comparable to that of cancer patients (4.66%) who are well-known at increased risk for VTE. Mutation carriers of F5/F2 had a significantly increased risk for VTE compared to non-mutation carriers, hazard ratio (HR) was 1.94, 95% confidence interval (CI): 1.42-2.65. In contrast, patients with the top PGS decile had a considerably higher risk for VTE compared to those with intermediate scores (middle 8 deciles), HR was 2.06 (95%CI: 1.57-2.71). The AUC for differentiating VTE diagnosis was 0.64 (95%CI: 0.61-0.67), 0.68 (95%CI: 0.66-0.71), and 0.69 (95%CI: 0.66-0.71), respectively, for F5/F2 mutation carriers, PGS, and combined. Similar to cancer patients, VTE complications are common in IBD patients. PGS provides more informative risk information than F5/F2 mutations (FVL and PGM) for personalized thromboprophylaxis.

P370 Correlation of the IBD Disk with intestinal ultrasound in patients with inflammatory bowel disease

Abstract Background The Inflammatory Bowel Disease (IBD) Disk represents a self-administered questionnaire that can facilitate, in real time, assessment of IBD related disability, and IBD-related daily life burden. Surrogate markers of IBD activity tend to associate with increased disability. Intestinal ultrasound (IUS) is a non-invasive tool that can objectively and accurately define disease activity and complications in IBD patients. We investigated the correlation between IBD-Disk and IUS in IBD patients. Methods We performed a cross-sectional study that included formally diagnosed IBD patients who underwent IUS and subsequently completed the IBD-Disk questionnaire. Active disease on IUS was defined as bowel wall thickness (BWT) >3 mm at the most affected bowel segment. The overall IBD-Disk score was calculated as the sum of its 10 components, ranging from 0 to 100 (best score: 0, worst score: 100). We explored the correlation between IBD-Disk and its components with IUS. We additionally investigated the correlation of IBD-related daily life burden with IUS. (IBD-Disk total score > 40: high IBD related daily life burden vs IBD-Disk total score ≤ 40: low IBD related daily life burden). Results We included 49 patients (table 1), who underwent IUS for disease monitoring (59.2%) and symptoms suggestive of disease flare (40.8%). Median IBD-Disk total score in our cohort was 48 (IQR 18-58). Median IBD-Disk total score was 52 (IQR 47.3-61.5) in IUS active vs 16 (IQR 5-25) in IUS inactive patients (p<0.001). The area under the ROC curve of IBD-Disk total score in predicting IUS activity was 0.88 (95% C.I: 0.77-0.99, p<0.001, Figure 1). IBD-Disk score >31 predicted disease activity in IUS with 90.6% sensitivity and 88.2% specificity. We observed a moderate correlation between IBD-Disk score and BWT (ρ=0.61, p<0.001) as well as between IBD-Disk score and C-reactive protein (ρ=0.66, p<0.001). Among the components of the IBD-Disk, 8/10 manifested a moderate correlation with BWT (table 2). IBD-Disk score > 40 was found in 27/32 (84.4%) of IUS active and 2/17 (11.8%) of IUS inactive patients, while IBD-Disk score ≤ 40 was found in 5/32 (15.6%) of IUS active and 15/17 (88.2%) of IUS inactive patients respectively (p<0.001). Median BWT was 1.95 mm (IQR 1.53-4.40) in patients with IBD-Disk score ≤ 40 and 5.9 mm (IQR 4.8-6.8) in patients with IBD-Disk score > 40 (p<0.001). Conclusion IBD-Disk displayed a significant correlation with IUS evidence of disease activity in IBD patients. Active disease in IUS was significantly correlated with a high IBD-related daily life burden as expressed by IBD-Disk total score > 40. IBD-Disk could be used in clinical practice to evaluate disease activity and severity in IBD patients.

The Effect of Anti-Tumor Necrosis Factor-Alpha Therapy within 12 Weeks Prior to Surgery on Postoperative Complications in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

The rate of abdominal surgical interventions and associated postoperative complications in inflammatory bowel disease (IBD) patients is still substantially high. There is an ongoing debate as to whether or not patients who undergo treatment with anti-tumor necrosis factor-alpha (TNF-α) agents may have an increased risk for general and surgical postoperative complications. Therefore, a systematic review and meta-analysis was conducted in order to assess the effect of anti-TNF-α treatment within 12 weeks (washout period) prior to abdominal surgery on 30-day postoperative complications in patients with IBD. The results of previously published meta-analyses examining the effect of preoperative anti-TNF-α treatment on postoperative complications reported conflicting findings which is why we specifically focus on the effect of anti-TNF-α treatment within 12 weeks prior to surgery. PubMed, Cochrane, Scopus, Web of Science, World Health Organization Trial Registry, ClinicalTrials.gov and reference lists were searched (June 1995−February 2022) to identify studies, investigating effects of anti-TNF-α treatment prior to abdominal surgery on postoperative complications in IBD patients. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated and subgroup analyses were performed. In this case, 55 cohort studies (22,714 patients) were included. Overall, postoperative complications (OR, 1.23; 95% CI, 1.04−1.45; p = 0.02), readmission (OR, 1.39; 95% CI, 1.11−1.73; p = 0.004), and intra-abdominal septic complications (OR, 1.89; 95% CI, 1.44−2.49; p < 0.00001) were significantly higher for anti-TNF-α-treated patients. Significantly higher intra-abdominal abscesses and readmission were found for anti-TNF-α-treated CD patients (p = 0.05; p = 0.002). Concomitant treatment with immunosuppressives in <50% of anti-TNF-α-treated patients was associated with significantly lower mortality rates (OR, 0.32; 95% CI, 0.12−0.83; p = 0.02). Anti-TNF-α treatment within 12 weeks prior to surgery is associated with higher short-term postoperative complication rates (general and surgical) for patients with IBD, especially CD.

S770 Risk of Cardiovascular, Thrombotic and Renal Complications After COVID-19 in Patients With Inflammatory Bowel Disease: A Propensity-Matched Cohort Study

Introduction: Studies have demonstrated that patients with Coronavirus disease 2019 (COVID-19) are at an increased risk of incident cardiovascular disease (CVD) including cerebrovascular disease, dysrhythmias, ischemic heart disease, myocarditis, pericarditis, heart failure and thromboembolic disease. Renal complications are also frequently reported in patients with COVID-19. Little is known regarding the short and long-term risk of COVID-19 related complications in patients with inflammatory bowel disease (IBD) Methods: We compared the 1 year risk of cardiac complications (arrhythmias, heart failure, myocarditis and pericarditis), venous thromboembolism (VTE), peripheral artery disease (PAD), ischemic stroke and acute kidney injury (AKI) in patients between IBD and non-IBD cohort after COVID-19 using TriNetX, a multi-institutional database. Sub-group analysis was performed based on vaccination status, disease activity and IBD medications. Active disease was defined as patients requiring IV or PO steroids or initiation of new biologic agent within 6 months prior to diagnosis of COVID-19. Patients with stable disease were steroid free or were not initiated on new biologic for at least 1 year prior to diagnosis of COVID-19. 1:1 propensity-score matching was performed for age, gender, race, ethnicity and all major risk factors of COVID-19 between all cohorts. Adjusted odds ratios (aOR) with 95% confidence interval (CI) were calculated. Results: The IBD cohort (n = 8,773) had an increased risk for cardiac complications (aOR 1.52, 95% CI 1.33 – 1.73), VTE (1.77, 1.53-2.04), ischemic stroke (2.04, 1.74 – 2.38), AKI (1.34, 1.14 – 1.58) and PAD (1.70, 1.34 – 2.15) after COVID-19 compared to non-IBD cohort. There was no difference between the vaccinated IBD cohort (≥2 vaccine doses) and vaccinated non-IBD cohort for composite outcome of CVD, VTE and AKI (aOR 1.28, 95% CI 0.52 – 3.15). Patients with active disease and COVID19 infection had a higher risk for cardiac complications, VTE and AKI (Figure). There was no difference in the risk of CVD, VTE or AKI in IBD patients on tumor necrosis factor inhibitor (TNFi), immunomodulators, non-TNFi and chronic prednisone compared to patients on 5-aminosalicyclic acid (5-ASA) (Table). Conclusion: Patients with IBD who are unvaccinated or with active disease are at an increased risk for CVD, thrombotic and renal complications after COVID-19. These patients may benefit from close follow up and aggressive CVD risk factor modification.Figure 1.: 1 year risk of CVD, thrombotic and renal complications in IBD patients after COVID-19 based on disease activity. Table 1. - Risk of CVD, thrombotic and renal complications after COVID-19 in IBD patients on TNFi, non-TNFi, chronic steroids and immunomodulators compared to 5-ASA Complication IBD medication (%) OR 95% CI TNFi 5-ASA Composite 10.79 10.83 0.99 0.64 – 1.52 Cardiac complication 8.36 7.52 1.12 0.70 – 1.77 VTE 4.60 3.72 1.24 0.70 – 2.22 Ischemic stroke 4.87 4.15 1.18 0.68 – 2.04 PAD 2.33 1.56 1.5 0.67 – 3.38 AKI 2.86 3.17 0.89 0.46 – 1.74 Immunomodulators 5-ASA Composite 14.14 14.06 1 0.68 – 1.47 Cardiac complication 8.50 11.30 0.72 0.48 – 1.08 VTE 6.90 6.50 1.06 0.71 – 1.60 Ischemic stroke 6.45 4.81 1.36 0.87 – 2.12 PAD 2.48 2.13 1.17 0.62 – 2.18 AKI 5.93 4.74 1.26 0.80 – 1.98 Non-TNFi 5-ASA Composite 12.50 12.50 1 0.55 – 1.79 Cardiac complication 8.15 11.62 0.67 0.36 – 1.24 VTE 4.74 3.86 1.24 0.54 – 2.81 Ischemic stroke 3.44 5.28 0.64 0.28 – 1.45 PAD 3.24 3.24 1 0.41 – 2.45 AKI 4.61 3.49 1.33 0.57 – 3.09 Steroid 5-ASA Composite 17.4 14.9 1.20 0.91 – 1.58 Cardiac complication 12.9 12.4 1.04 0.80 – 1.137 VTE 7.6 7.2 1.05 0.79 – 1.40 Ischemic stroke 7.9 6.07 1.33 0.99 – 1.78 PAD 2.3 2.1 1.09 0.69 – 1.74 AKI 7.01 5.97 1.18 0.87 – 1.61

Urotensin II levels in patients with inflammatory bowel disease.

BACKGROUNDPatients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIMTo determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters.METHODSThis cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn’s disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer’s instructions.RESULTSIBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn’s disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn’s Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030).CONCLUSIONIt is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.

Systematic review and meta-analysis: risks of postoperative complications with preoperative use of anti-tumor necrosis factor-alpha biologics in inflammatory bowel disease patients.

The preoperative use of anti-tumor necrosis factor-alpha (anti-TNF) in inflammatory bowel disease (IBD) patients undergoing surgery has been controversial due to concern for increased risks of postoperative complications. We aimed to determine the effect of preoperative anti-TNF therapy on postoperative complications in IBD patients undergoing abdominal surgery. A literature search of Google Scholar, PubMed, The Cochrane Library, EMBASE, and CINAHL was performed through October 2019. Studies reporting postoperative complication rates of Crohn's disease (CD), ulcerative colitis (UC), and IBD-unspecified patients with preoperative anti-TNF treatment undergoing abdominal surgery compared to controls without preoperative anti-TNF treatment were included. The main outcomes measured were overall, infectious, and noninfectious postoperative complications. Forty-one studies totaling 20 274 patients were included. There was a significant increase in overall complications in all patients treated with anti-TNF vs. controls [odds ratio (OR) = 1.13, 95% confidence interval (CI), 1.01-1.25, P = 0.03, I2 = 6%] with an absolute risk increase (ARI) of 5.5% and a number needed to harm (NNH) of 18. There was also a significant increase in infectious complications in CD patients (OR = 1.44; 95% CI 1.02-2.03, P = 0.04, I2 = 49%, ARI = 5.5%, NNH = 20) only. Contrastingly, there was a significant increase in noninfectious complications in all patients (OR = 1.44, 95% CI 1.13-1.85, P = 0.003, I2 = 8%, ARI = 6.4%, NNH = 16) and UC patients (OR = 1.57, 95% CI 1.15-2.14, P = 0.005, I2 = 25%, ARI = 8.5%, NNH = 12) only. Preoperative use of anti-TNF agents in IBD patients undergoing abdominal surgery is associated with increases in overall postoperative complications in all patients, infectious postoperative complications in CD patients, and noninfectious postoperative complications in UC patients.

The New Proactive Approach and Precision Medicine in Crohn's Disease.

The proactive approach to Crohn’s disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.

P746 Prevalence, features and outcomes of splachnic vein thrombosis in inflammatory bowel disease. A nationwide, retrospective study from the ENEIDA registry

Abstract Background The risk of splanic vein thrombosis (SVT) -as defined as that involving the portal vein and/or its intrahepatic branches, mesenteric, splenic and/or suprahepatic veïns is mainly observed, among others, in inflammatory abdominal conditions. Thromboembolic complications are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, characteristics, risk factors and evolution of SVT in patients with IBD. Our aims were to describe the characteristics of SVT in patients with IBD, diagnostic explorations, treatment and evolution. Methods Retrospective, multicentre, descriptive study of the ENEIDA registry with a diagnosis of SVT. In addition to epidemiological and clinical features of IBD, we recorded specifically diagnosis, treatment, disease activity at the time of SVT and outcome of SVT. Results Over 59,000 IBD patients in the ENEIDA registry, only 49 episodes of SVT were identified (35 Crohn’s / 14 Ulcerative Colitis); 69% men, median age 42 years old, 35% smokers. 37% had a past history of surgery and/or abdominal inflammatory conditions, 16% extra-intestinal neoplasia, 23% baseline immune or hematologic conditions and 14% liver disease. Finally, 16% had a previous episode of venous thrombosis. The most frequent forms of clinical presentation were abdominal pain with/without fever (59%), and radiological findings in the setting of active IBD (25%). ST coincided with IBD activity in 76% of cases. The diagnosis of SVT was based in the findings of an abdominal CT in 82%. The most frequent localition of SVT were intrahepatic portal branches (51%) and superior mesenteric vein (47%). Only 47% had a basic aetiological study, and 37% underwent gastroscopy (median 7 months from the diagnosis of SVT) showing oesophageal varices in 67%. Anticoagulation therapy was prescribed in 94% of the episodes (74% within the first month since diagnosis), for a median of 7 months. In 90% of the cases, there was a further radiological assessment, 61% of which showing the resolution of the SVT (median of 5 months from the beginning anticoagulation treatment). Conclusion SVT seems to be a rare (or underdiagnosed) complication in IBD patients, it is mostly associated with disease activity and evolves suitably when anticoagulation therapy is suitably started.

P753 Elevation of liver enzymes in a large cohort of patients with inflammatory bowel disease

Abstract Background Elevation in liver enzymes (ELE) is often seen in patients with inflammatory bowel disease (IBD). The aim of this study is to assess the incidence, character, chronicity, degree, and etiology of ELE in within the validated epiIIRN cohort which includes all IBD patients in Israel (n = 45,074). Methods We current analysis was performed on data from three of four Health Maintenance Organisations (HMOs), covering 48% of the Israeli population. The identification of Crohn’s disease (CD) and ulcerative colitis (UC) utilised previously validated algorithms. Retrieved data included demographics, anthropometric measures, liver enzymes, medications and other diagnoses codes. Mild ELE was defined from upper normal limit (UNL) to X2 UNL, moderate X3 UNL and severe elevation ≥X4 UNL). The pattern of elevation was defined as hepatocellular (isolated elevation of ALT and/or AST), cholestatic (elevated GGT and/or ALK and bilirubin) and mixed pattern. Chronicity of ELE was defined as brief (&amp;lt;30 days) to chronic (&amp;gt;180 days). Results The total incidence (ever) of ELE in CD patients was 33% (3098/9421) and 28% in UC (2001/7040); p &amp;lt; 0.001. The mean age at ELE was 29.9 years (IQR 17.2–47.5) in CD and 37.9 years (23.2–53.8) in UC (p &amp;lt; 0.001). Hepatocellular pattern had more commonly in UC (54% vs. 47%, p &amp;lt; 0.001) as mixed pattern (22% vs. 20%, p = 0.01), while cholestatic pattern had more commonly in CD (31% vs. 26%, p &amp;lt; 0.001). The ELE was transient in 609 (9%) patients, while 4054 (62%) had chronic ELE. Mild ELE was recorded in 860 (22%) CD patients and 460 (19%) UC, and severe in 328 (8%) CD and 253 (10%) UC. ELE was recorded during the first three months after initiation of thiopurines in 604 (15%) CD and 201 (8%) UC patients (p &amp;lt; 0.001), after biologics in 346 (9%) CD and 62 (3%) UC (p &amp;lt; 0.001), after steroids in 538 (14%) and 272 (11%), respectively (p = 0.01) and after methotrexate in 76 (2%) and 15 (0.6%), respectively (p = 0.001). The incidence of fatty liver was most common in UC (5% vs. 3%, p = 0.006). Conclusion ELE is common complication in IBD patients, more so in UC. When enzymes do increase in CD they tend to reach higher levels. Drug induced liver injury was more common in CD. This study was supported by a grant from the Leona M. and Harry B. Helmsley Charitable Trust.

2518 Transitory Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) in a Child With Very Early Onset (VEO) of Ulcerative Colitis (UC) Complicated With Primary Sclerosing Cholangitis (PSC)

INTRODUCTION: VEO - Inflammatory bowel disease (IBD), in children younger than 6 years of age, is frequently associated with a more severe course and distinct genetic profile compared with later onset IBD. We report the case of a child with VEO - UC complicated with PSC and HLH/MAS. CASE DESCRIPTION/METHODS: A 10-year-old male, presented with bloody diarrhea, hepatomegaly and elevated transaminases when he was 30 months old. He had moderate pancolitis associated with C difficile (Cdiff) infection. He improved after metronidazole and sulfasalazine (SFZ) treatment. Two months later, he had hematochezia and endoscopic worsening of his colitis, which improved after discontinuing SFZ and receiving steroids and 6-MP. MRCP was consistent with PSC (Figure 1) and he was started on ursodiol. At ∼ 7 years of age, while receiving treatment with 6MP and Infliximab, he was hospitalized due to fever, hepatomegaly, diarrhea and pancytopenia. Blood and stool cultures, and tests for Cdiff, EBV, CMV, rota and parvovirus were negative. Triglyceride and ferritin levels were normal. He improved clinically and his pancytopenia resolved after 5 days of empirical antibiotic treatment (AbTx). Bone marrow biopsy (BMBx) was deferred. Metabolites of 6MP were normal but 6MP was held temporarily. Six months later, he had fever and diarrhea associated with pancytopenia and high levels of ESR, CRP, ferritin, triglyceride and interleukin 2 receptor. Number and function of NK cells were decreased. Stools and blood cultures, and tests for EBV, HSV and CMV were negative. Cdiff stool antigen was positive but PCR was negative. BMBx showed histiocytosis and erythophagocytosis (Figure 2). Lymphocyte flow cytometry was negative for lymphoproliferative disorder. After AbTx he improved and pancytopenia and ferritin level corrected within one week. Routine immunodeficiency tests were normal. Gene mutations associated with familial HLH: PRF1, Rab27A, SH2D1A, STX11, STXBP2, UNC 13D and XIAP were negative. 6MP was held. Infliximab initially, and subsequently Adalimubab, were discontinued because of high antibodies and allergic reactions. Five months later 6MP was restarted. He has been in remission of UC for 16 months. DISCUSSION: HLH/MAS is a very rare, potentially fatal complication in IBD patients. Our patient has a history of VEO - UC, PSC and two episodes of pancytopenia not associated with EBV or CMV - one of which fulfilled criteria for HLH/MAS. Remarkably, he recovered within one week after empirical AbTx without steroids or other treatment for HLH/MAS.

Renal and Urinary Manifestations of Inflammatory Bowel Disease

The incidence of inflammatory bowel disease (IBD) is increasing rapidly and extra-intestinal manifestations in IBD are also increasing. The prevalence of renal and urinary involvement in IBD ranges from 4-23%. Nephrolithiasis is the most common urinary complication in IBD patients. Parenchymal renal disease is rare but has been well documented and presents most commonly as glomerulonephritis or tubulointerstitial nephritis. The overall morbidity of IBD-related renal manifestations is significant. Therefore, a high index of clinical suspicion and optimal monitoring of the renal function are needed for the early diagnosis and prevention of IBD-related renal manifestations and complications.

Increased Risk of Influenza and Influenza-Related Complications Among 140,480 Patients With Inflammatory Bowel Disease.

Diseases of immune dysregulation are associated with an increased risk of viral infections, some of which may be preventable. To date, there are very limited data on the incidence and risk of influenza and related complications in patients with inflammatory bowel disease (IBD). Furthermore, the impact of immunosuppressive medications on that risk is unclear. Therefore, the aim of this study was to estimate the incidence and severity of influenza infections in IBD patients. In addition, we looked specifically at the effect of medications on influenza risk. Using the MarketScan Database (January 2008 to December 2011), we conducted a retrospective cohort study to estimate the incidence of influenza and risk of related complications in IBD patients compared with those without IBD. We employed a nested case-control study design to evaluate the potential independent effect of IBD medications on influenza risk. A total of 140,480 patients with IBD and non-IBD controls were studied. There were 2963 patients with influenza compared with 1941 non-IBD subjects. Inflammatory bowel disease patients had an increased influenza risk compared with those without IBD (incidence rate ratio, 1.54; 95% confidence interval [CI], 1.49-1.63). A higher rate of hospitalizations (162/2994 [5.4%] vs 36/1941 [1.85%]; P < 0.001) was noted. Systemic corticosteroids were found to be independently associated with influenza (odds ratio, 1.22; 95% CI, 1.08-1.38). Inflammatory bowel disease patients had an increased risk of influenza compared with those without IBD and were more likely to require hospitalization. Steroids were the only medication class independently associated with flu risk.

Systematic Review and Meta-analysis: Vedolizumab and Postoperative Complications in Inflammatory Bowel Disease.

Several studies have reported the surgical outcomes of inflammatory bowel disease (IBD) patients exposed to vedolizumab (VDZ) preoperatively, with conflicting results. This meta-analysis aims to evaluate the risk of postoperative complications in IBD patients preoperatively exposed to VDZ in comparison with patients exposed to anti-tumor necrosis factor (anti-TNF) treatment or no biologic therapy. A systematic review with a meta-analysis of the existing literature was conducted. The main outcomes included the odds of developing overall postoperative complications, infectious complications, surgical site infections, need for repeat surgery, and major postoperative complications, as defined by the Clavien-Dindo criteria. Four studies were included in the meta-analysis. The risk of all postoperative complications was not significantly different between IBD patients exposed preoperatively to VDZ vs anti-TNFs (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.21-1.88). In patients with ulcerative colitis (UC), the OR for complications was significantly lower in VDZ-exposed as opposed to anti-TNF-exposed patients (OR, 0.35; 95% CI, 0.14-0.85); the comparison was insignificant in Crohn's disease. There were no significant differences in the risk of infectious complications, surgical site infections, need for reoperation, or major surgical complications in patients exposed to VDZ vs anti-TNFs. There were no significant differences in outcomes when comparing patients exposed to VDZ with those not given biologic therapy. This meta-analysis did not detect an increased risk of postoperative complications with preoperative VDZ exposure; the risk of overall complications may be lower in UC patients in comparison with those with anti-TNF exposure. These results merit further verification in future studies.

The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

Validation and optimization of the Systemic Inflammation-Based modified Glasgow Prognostic Score in predicting postoperative outcome of inflammatory bowel disease: preliminary data

Systemic Inflammation-Based modified Glasgow Prognostic Score (mGPS) was developed as an objective tool to grade state of inflammation. However, the association between mGPS and postoperative complications for inflammatory bowel disease (IBD) patients was still unknown. In our study, 270 IBD patients [Crohn’s disease (CD), n = 186; Ulcerative colitis (UC), n = 84] from January 2013 and January 2016 who underwent elective bowel resection were retrospectively analyzed, and, the levels of preoperative C-reactive protein (CRP) and albumin were included as parameters of mGPS. The incidence of overall postoperative complications was 44.81% (121/270), including 46.77% (87/186) of CD and 40.48% (34/84) of UC. According to multivariate analysis, mGPS (CD: OR = 3.47, p = 0.003; UC: OR = 3.28, p = 0.019) was independently associated with an increased risk of postoperative complications. Patients with a higher mGPS also suffered longer postoperative stay and increased SSIs (both p < 0.05). Combining mGPS with neutrophil ratio improved its prognostic value with a better area under the curve (AUC), using receiver operating characteristic (ROC) method. Then we confirmed that mGPS was associated with postoperative complications in IBD patients undergoing elective bowel resection and the addition of neutrophil ratio enhanced its prognostic value.

Infectious Complications in Liver Transplant Patients Exposed to Vedolizumab for the Treatment of Inflammatory Bowel Disease

Introduction: Vedolizumab, a gut-selective antibody to α4β7 integrin, received FDA approval in May 2014 for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD). While integrated safety data from 6 trials of vedolizumab found low incidence of serious infections, there has yet to be published reports of infectious complications in an immunosuppressed population. Methods: Retrospective analysis of all patients with inflammatory bowel disease (IBD) who underwent liver transplant for primary sclerosing cholangitis (PSC) was performed. Patients exposed to vedolizumab post-liver transplant for the treatment of UC or CD were included. Data collected included patient demographics, IBD characteristics, vedolizumab treatment and duration, immunosuppression regimens for prevention of liver rejection, and infectious complications during vedolizumab therapy. Results: A total of 9 patients (6 UC, 3 CD) were included (Table 1). Eight (89%) were male; median age was 51 years (IQR 42 to 57). Indication for liver transplantation was PSC (n=6) or PSC-related cholangiocarcinoma (n=3). Patients were most commonly on tacrolimus (n=8, 89%) with or without prednisone (n=4, 67%) for prevention of rejection. Vedolizumab was initiated a median of 6 years (IQR 2-12 years) following liver transplantation. Patients had a median exposure time of 5 months (IQR 4.5-11.5 months) to vedolizumab at the time of data collection; the majority of patients (n=6, 67%) were on maintenance therapy as defined by receiving > 4 doses. Concurrent use of steroids and immunomodulator was 33% (n=3) and 0%, respectively. During exposure to vedolizumab, 6 patients (67%) experienced a total of 11 infections (Table 2): acute cholangitis (n=2, 4 infections), Clostridium difficile infection (n=2, 2 infections), and 5 other infections each with one occurrence. Three patients experienced infections that required four hospitalizations and one surgery: acute cholangitis requiring common bile duct stent placement (1) and ERCP for stent exchange (1), C. difficile infection requiring intravenous antibiotics, and a small bowel perforation with resultant fecal peritonitis and intra-abdominal abscess requiring surgical repair of perforation drainage of abscesses.Table: Table. Baseline characteristics of individuals with inflammatory bowel disease post-liver transplant on vedolizumabTable: Table. Infections in individuals with inflammatory bowel disease post-liver transplant on vedolizumabConclusion: Two-thirds of immunosuppressed IBD patients in our cohort of post-liver transplant individuals experienced infectious complications after initiation of vedolizumab. Larger case-control studies are needed to assess the risk of infectious complications in IBD patients receiving concurrent immunosuppressive therapy.