Clinical Course Of Ulcerative Colitis Research Articles

Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis-results from the IBSEN III inception cohort.

The introduction of biologic therapies and the 'treat-to-target' treatment strategy may have changed the disease course of ulcerative colitis (UC). To describe the early disease course and disease outcome at 1-year follow-up in a population-based inception cohort of adult patients with newly diagnosed UC. The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study with prospective follow-up. Patients newly diagnosed with inflammatory bowel disease during 2017-2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1-year follow-up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1-year follow-up. We included 877 patients with UC (median age 36 years (range: 18-84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left-sided colitis and 36.0% extensive colitis. At the 1-year follow-up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid-free clinical remission was observed in 76.6%, and steroid-free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. In this population-based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1-year follow-up. The use of biologic therapy increases, consistent with findings from previous studies.

Influence of vitamin D receptor signaling and vitamin D on colonic epithelial cell fate decisions in ulcerative colitis.

Epidemiological studies have shown that subnormal levels of vitamin D (25(OH)D) are associated with a more aggravated clinical course of ulcerative colitis (UC). Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor (VDR) signaling, the mechanisms underlying the effects of the vitamin D-VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25(OH)2D3)/VDR signaling in human organoids could influence the maintenance of the colonic epithelium. Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterize the functional and transcriptional effects of 1,25(OH)2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9. Our results suggest that 1,25(OH)2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25(OH)2D3/VDR signaling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC. We identified an important role of vitamin D signaling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D-VDR signaling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC.

Clinical statistical analysis plan for the ACCURE trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial

BackgroundThe primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial.Design and methodsThe ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life.DiscussionThe ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients.Trial registrationDutch Trial Register (NTR) NTR2883. Registered May 3, 2011. ISRCTN, ISRCTN60945764. Registered August 12, 2019.

P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative Colitis

Abstract Background Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors. Methods We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC&amp;lt;6.2 were defined as low MUC group and others as high MUC group. Results A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups. Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups. Conclusion Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.

P955 The effect of appendicectomy on the clinical course of Ulcerative Colitis: Preliminary results

Abstract Background Emerging evidence indicates an immunomodulatory role of the appendix in ulcerative colitis (UC). Previous studies have suggested a beneficial effect of appendicectomy in inducing and maintaining remission. Therefore, appendicectomy may be considered as an alternative or adjunctive treatment in UC. Aim To evaluate the efficacy of appendicectomy in maintaining remission in UC patients. Methods Adult patients with established UC in complete clinical and endoscopic remission (defined as Mayo score &amp;lt;3 with endoscopic subscore of 0 or 1) following medical induction treatment for disease relapse within 12 months prior to randomisation, were enrolled in the Netherlands and United Kingdom. Patients were randomised (1:1) to undergo appendicectomy (intervention group) or continue maintenance medical therapy (control group). The primary outcome was the one-year UC relapse rate (defined as a total Mayo-score score ≥5 with endoscopic subscore of ≥2). To detect a clinically relevant decrease in relapse rate from 40% to 20%, 82 patients per study arm were needed to achieve 80% power. The last patient was included in September 2022, so analysis of the primary outcome parameter is expected to start soon. Trial progress, including the accumulated number of (serious) adverse events (SAE) in both groups, were presented annually to the Data Safety Monitoring Board. Therefore safety data is available. Results In total, 99 patients were included in the intervention group and 99 patients in the control group. There were 86 males and 112 females, with a median age of 41 years (IQR 33-52). Baseline characteristics were comparable in both groups, with the majority of patients having proctitis (38.9%) or left sided colitis (35.9%). Three SAEs were reported in the appendicectomy group, 2 of which were related to the surgical procedure (reintervention for obstructive ileus and postoperative hematoma) and one hospitalisation for clostridium infection. One SAE was reported within the first year in the control group (appendicitis). The one-year reported colitis-associated adverse event rate was significantly lower in the appendicectomy group when compared to the control group (46.4% vs. 63.9%, P=0.02). During follow up there were no colectomies in the appendicectomy group, whereas three patients underwent colectomy for therapy-refractory disease in the control group. Conclusion Appendicectomy in patients with UC has the possibility to decrease the rate of colitis-associated (serious) adverse events. These results suggest that the final analysis of the primary outcome parameter (relapse rate) could demonstrate that appendicectomy is superior to standard medical therapy alone in maintaining remission in these patients.

Linking microbial genes to plasma and stool metabolites uncovers host-microbial interactions underlying ulcerative colitis disease course

Understanding the role of the microbiome in inflammatory diseases requires the identification of microbial effector molecules. We established an approach to link disease-associated microbes to microbial metabolites by integrating paired metagenomics, stool and plasma metabolomics, and culturomics. We identified host-microbial interactions correlated with disease activity, inflammation, and the clinical course of ulcerative colitis (UC) in the Predicting Response to Standardized Colitis Therapy (PROTECT) pediatric inception cohort. In severe disease, metabolite changes included increased dipeptides and tauro-conjugated bile acids (BAs) and decreased amino-acid-conjugated BAs in stool, whereas in plasma polyamines (N-acetylputrescine and N1-acetylspermidine) increased. Using patient samples and Veillonella parvula as a model, we uncovered nitrate- and lactate-dependent metabolic pathways, experimentally linking V.parvula expansion to immunomodulatory tryptophan metabolite production. Additionally, V.parvula metabolizes immunosuppressive thiopurine drugs through xdhA xanthine dehydrogenase, potentially impairing the therapeutic response. Our findings demonstrate that the microbiome contributes to disease-associated metabolite changes, underscoring the importance of these interactions in disease pathology and treatment.

Appendectomy and Risk of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study.

The aim of this study was to examine the association between appendectomy and advanced colorectal neoplasia (aCRN) in patients with inflammatory bowel disease (IBD). Inflammatory bowel disease patients diagnosed in Denmark in the period 1977 to 2017 were identified from the Danish National Patient Registry. Inflammatory bowel disease patients who underwent appendectomy were matched with up to 10 IBD patients without appendectomy and followed until aCRN, death, or emigration. Absolute risks of aCRN were calculated, treating death and bowel resections as competing risks. Stratified Cox regression was used to calculate adjusted hazard ratios (aHRs) of aCRN, comparing IBD patients with appendectomy to IBD patients without appendectomy. We identified 3789 IBD patients with appendectomy and 37 676 IBD patients without appendectomy. A total of 573 patients (1.4%) developed aCRN, with an absolute risk of aCRN at 20 years of 4.9% (95% confidence interval [CI], 2.9%-7.7%) for ulcerative colitis (UC) patients with appendectomy after UC diagnosis compared with 2.8% (95% CI, 2.3%-3.3%) for UC patients without appendectomy. Appendectomy after UC was associated with an increased rate of aCRN 5 to 10 years (aHR, 2.5; 95% CI, 1.1-5.5) and 10 to 20 years after appendectomy (aHR, 2.3; 95% CI, 1.0-5.5). Appendectomy prior to UC diagnosis was not associated with an increased rate of aCRN, and Crohn's disease was not associated with the rate of aCRN, regardless of timing or histological diagnosis of the appendix specimen. Although appendectomy may have a positive effect on the clinical course of UC, our study suggests that this may come at the expense of a higher risk of aCRN.

Impact of Dextran-Sodium-Sulfate-Induced Enteritis on Murine Cytomegalovirus Reactivation.

(1) Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the intestines, which participates in human cytomegalovirus (HCMV) reactivation from its latent reservoir. CMV-associated colitis plays a pejorative role in the clinical course of UC. We took advantage of a model of chemically induced enteritis to study the viral reactivation of murine CMV (MCMV) in the context of gut inflammation. (2) Methods: Seven-week-old BALB/c mice were infected by 3 × 103 plaque-forming units (PFU) of MCMV; 2.5% (w/v) DSS was administered in the drinking water from day (D) 30 to D37 post-infection to induce enteritis. (3) Results: MCMV DNA levels in the circulation decreased from D21 after infection until resolution of the acute infection. DSS administration resulted in weight loss, high disease activity index, elevated Nancy index shortening of the colon length and increase in fecal lipocalin. However, chemically induced enteritis had no impact on MCMV reactivation as determined by qPCR and immunohistochemistry of intestinal tissues. (4) Conclusions: Despite the persistence of MCMV in the digestive tissues after the acute phase of infection, the gut inflammation induced by DSS did not induce MCMV reactivation in intestinal tissues, thus failing to recapitulate inflammation-driven HCMV reactivation in human UC.

Depression is associated with increased disease activity in patients with ulcerative colitis: A propensity score-matched analysis using a nationwide database in Japan.

The incidence and prevalence of psychiatric disorders are elevated in patients with inflammatory bowel disease (IBD). Whether psychiatric disorders could affect the clinical course of IBD is uncertain and controversial. We aimed to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD using a nationwide database in Japan. We collected data on admissions with IBD using the Diagnosis Procedure Combination database system introduced in Japan. We divided eligible admissions into IBD with and without depression groups using propensity score matching and compared the rates of surgery, use of molecular targeted drugs and biologics, systemic steroid administrations, and in-hospital death. We also conducted a logistic regression analysis to identify clinical factors affecting surgery, the use of molecular targeted drugs and biologics, and systemic steroid administrations. The rates of surgery, use of two or more molecular targeted drugs, systemic steroid administrations, and in-hospital deaths in the ulcerative colitis (UC) with depression group were higher than in the UC without depression group. Multivariate analysis of UC showed that depression increased the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery. However, analysis of Crohn's disease showed that only steroid administrations were associated with depression. Our study demonstrated an association between a worse clinical course of UC and depression. Although this result indicates that depression might be associated with increased disease activity in patients with UC, the causal relationship is still unclear. Further prospective studies are warranted.

How has the disease course of pediatric ulcerative colitis changed throughout the biologics era? A comparison with the IBSEN study.

BACKGROUNDIn Korea, infliximab was approved for use in children with ulcerative colitis (UC) in October 2012. AIMTo compare the clinical course of UC before and after the introduction of biological agents, and to compare with the IBSEN study. METHODSPatients under 18 years of age, who were diagnosed with UC and followed from January 2003 to October 2020, were included in the study. Group A (n = 48) was followed for at least 2 years between January 2003 and October 2012, and Group B (n = 62) was followed for at least 2 years between November 2012 and October 2020. We compared endoscopic remission, drug composition, relapse rate, steroid-free period, and the quality of life of each group. We plotted the clinical course of the included patients using the pediatric UC activity index score, and compared our patients with those in the IBSEN study. RESULTSAfter 2 years of treatment, colonoscopy evaluation revealed different outcomes in the two treatment groups. Remission was confirmed in 14 patients (29.2%) of Group A, and in 31 patients (50.0%) of Group B (P < 0.012). The median cumulative corticosteroid-free period was 3.0 years in Group A and 4.4 years in Group B. Steroid-free period of Group B was significantly longer than that of Group A (P < 0.001). There was a statistically significant difference between the two groups in evaluation of the relapse rate during the observation period (P < 0.001). The plotted clinical course graphs of Group A showed similar proportions to the graphs in the IBSEN study. However, in Group B, the proportion of patients corresponding to curve 1 (remission or mild severity after initial high activity) was high at 76% (47/62). CONCLUSIONThe incidence of relapse has decreased and the steroid-free period has increased after the introduction of the biological agent. The clinical course also showed a different pattern from that of IBSEN study. The active use of biological agents may change the long-term disease course in moderate to severe pediatric UC.

Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour

BackgroundThe clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour.MethodsUC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses.ResultsTwenty-four UC patients were included (age [median, range]) 55 [21–72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016).ConclusionReduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.

Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study

PurposeThe clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC.MethodsEPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months.ResultsOf the 307 out of 311 participants (4 patients did not meet the inclusion criteria “confirmed diagnosis of active UC within the last 6 months” (n = 2) and “immunosuppressive-naïve” (n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p < 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed.ConclusionOur study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.

P130 Comparison of the clinical course of Ulcerative Colitis according to the presence or absence of clinical symptoms at the time of diagnosis

Abstract Background Asymptomatic ulcerative colitis (UC) is increasingly detected by improved screening tests such as the fecal immunochemical test. However, there have been few reports on the difference in the clinical course of UC according to the presence or absence of symptoms at diagnosis. The purpose of this study was to compare the clinical course of UC according to the presence or absence of clinical symptoms at the time of diagnosis. Methods Data were obtained from a retrospective chart review of 64 consecutive patients with UC diagnosed at our hospital between 2014 and 2020. Patients were grouped according to the presence or absence of clinical symptoms at the time of UC diagnosis, and clinical characteristics (age, sex, extent of disease, Mayo Score, endoscopic severity, and hematological findings) at the time of diagnosis were subjected to univariate and multivariate analyses. In the clinical characteristics, propensity score matched analysis was performed, and systemic steroids use, hospitalization within 1 year, and the introduction of therapies for refractory UC were evaluated. Patients with a clinical course of less than 1 year after UC diagnosis, patients intolerant to 5-aminosalicylic acid, patients with carcinoma, pregnant women, and patients under 15 years of age were excluded. Results Eligible patients were 64 UC patients (19 asymptomatic and 45 symptomatic) diagnosed at our hospital during the period of the study. The symptomatic group included 32 cases of bloody stools, 30 cases of diarrhea, 7 cases of abdominal pain, and 4 cases of fever. Multivariate analysis of clinical features at diagnosis showed significant differences in Mayo Score (p=0.003, odds ratio: 3.650, 95% confidence interval: 1.541–8.647) and serum hemoglobin level (p=0.021, odds ratio: 0.367, 95% confidence interval: 0.157–0.859). As a result of propensity score matched analysis, 24 patients (12 asymptomatic, 12 symptomatic) were selected. There were no significant differences in the rates of systemic steroid use (16.7% vs. 16.7%), hospitalization within 1 year (16.7% vs. 8.3%), and the introduction of therapies for refractory UC (16.7% vs. 8.3%) between the two groups (p=1.000 in all items). Conclusion There was no difference in the prognosis of the asymptomatic group compared with the symptomatic group using propensity score matched analysis. The results suggest that asymptomatic UC detected by colonoscopy may be acceptable for follow-up without treatment.

P455 Aminosalicylates in Ulcerative Colitis: old but gold?

Abstract Background The clinical course of ulcerative colitis (UC) is characterized by periods of exacerbation and remission. 5-aminosalicylic acid (5-ASA) remains the treatment of choice in patients with mild-to-moderate UC, due to its beneficial effect in preventing relapse. Treatment options (immunomodulators [IMM] and biological agents) have increased, so it is important recognizing patients at risk of medical therapy failure that can appropriately optimize treatment escalation for better control of the disease. Little is known about the long-term course of the disease among patients in remission with 5-ASA. Aims To assess long-term efficacy of 5-ASA (no IMM, biological therapy or colectomy) and to identify predictive factors of non-response. Methods An observational, retrospective, single-centre, case-control study was performed. All consecutive patients with UC followed in our Hospital from January 2000 until June 2020 initially treated with 5-ASA (±steroids) with a minimum follow-up of 1 year were screened for eligibility. Exclusion criteria were 5-ASA toxicity/intolerance or initial treatment with IMM/biologic agents.Time until step-up was recorded. Demographic, clinical, endoscopic, biochemical, and histological variables at the diagnosis were recorded and a Cox regression was performed to identify predictive factors for step-up strategy. Results 218 patients (mean age 41,4±14,6 years; 54,5% female; mean follow-up10,1±1,9 years) were analysed, 28% needed treatment with biologics or IMM, mainly due to steroid-dependence. Among “5-ASA responders”, 72% and 48% had sustained endoscopic and histological remission, respectively. The probability of step-up at 1 year, 5 years and 10 years was 10, 18 and 25%, respectively. “Step-up patients” had higher rates of hospitalization, disease extent progression, extraintestinal manifestations and colonic stenosis and/or pseudo-polyps (p&amp;lt;0,05). Montreal E3 (HR:2,31;95% CI: 1,12-4,68), steroids at first flare (HR:3,45;95% CI: 1,26-7,29), lower 5-ASA maintenance dose (HR: 1,97;95%;CI:1,12-3,29), lower haemoglobin level (HR:1,45;95% CI: 1,11-3,24) and DUBLIN Score≥4 (HR:1,81;95% CI: 1,269-4,59) were factors associated with the step-up strategy, in multivariate analysis. Conclusion 5-ASA is an effective maintenance therapy; a satisfactory response was achieved in 72% of the patients after a mean time of follow-up of 10 years. Extensive colitis, higher DUBLIN Score, lower doses of 5-ASA, need for steroid and anaemia can predict a worse prognosis at the initial diagnosis and are associated with higher therapeutic requirements. These findings may be used in our clinical practice to identify patients that might benefit from an early step-up approach and minimize the morbidity associated with uncontrolled disease.

Analysis of the disease activity of ulcerative colitis with and without concomitant primary sclerosing cholangitis: An investigation using a nationwide database in Japan.

AimsPrimary sclerosing cholangitis (PSC) is a relatively common complication of ulcerative colitis (UC). Only a few studies have investigated the impact of PSC on the clinical course of UC, and their conclusions are contradictory. Therefore, we aimed to compare the disease activity of UC with and without PSC.Methods and ResultsWe collected UC patient data using the Diagnosis Procedure Combination database system in Japan and classified eligible admissions into two groups based on their diagnosis of either UC alone or UC associated with PSC. We then compared therapeutic details (medical treatment and surgery) between the two groups. Multivariable logistic regression analysis and propensity score matching was also performed. The rates of systemic steroid injection and infliximab administration in patients with PSC were lower than those in patients without PSC (21% vs. 28%, P = 0.012, 9.6% vs. 16%, P = 0.01, respectively). The rates of surgery, colorectal cancer, duration of hospital stay, and in‐hospital mortality did not differ between the two groups. Multivariable analysis revealed that concomitant PSC was a clinical factor that reduced the odds of systemic steroid injection (odds ratio [OR] = 0.66, 95% confidence interval [CI]: 0.49–0.90, P = 0.008) and infliximab (OR = 0.48, 95% CI: 0.32–0.74, P = 0.0008) administration.ConclusionUC patients with PSC might have less UC disease activity than those with UC alone.

Effects of tissue cytomegalovirus quantitative polymerase chain reaction in the management of ulcerative colitis flare-ups: Should we wave aside?

Background and Study AimsThe role of cytomegalovirus (CMV) infection for disease reactivation in ulcerative colitis (UC) patients remains controversial and diagnostic tests are yet to be standardized. We aimed to define the clinical relevance of CMV detection by mucosal polymerase chain reaction (PCR) in UC patients by comparing the clinical course of UC in CMV-treated and CMV-untreated groups in tissue CMV-PCR positive cases. Patients and MethodsIn this retrospective study, 141 patients diagnosed with moderate-to-severe UC admitted to our clinic with disease flare, colonic tissue CMV PCR was assessed. ResultsThe median age of the study population was 39 years, and 99 (70.2%) patients were male. Eighty-eight (62.4%) patients were CMV-PCR (+) and 53 (37.6%) were CMV PCR (-). The CMV-PCR (+) and CMV PCR (-) groups showed no significant difference concerning age, sex, disease duration, site of involvement and disease activity and administered treatments. The median tissue CMV-PCR was 41,098 IU/mL (IQR:2,344.25–136,192). Thirty-four of 88 CMV-PCR (+) patients received antiviral therapy. The tissue CMV-PCR level of patients who received antiviral therapy was 124,381 IU/mL (IQR: 19,309–412,335), and it was 6,292 IU/mL (IQR: 997–71,154) in patients who did not receive antiviral therapy; (p < 0.001). Sixteen (47.1%) of 34 patients who received antiviral therapy achieved remission. Two of the non-responders underwent colectomy (one because of dysplasia and one who did not respond subsequent biologic agent either). Remaing 16 achieved remission by escalating the immunsuppresive/biologic agent therapy. ConclusionCMV infection is responsible for only a minority of cases of UC flares and all are steroid-resistant cases. Most of the patients non-responsive to antiviral treatment respond to increased anti-inflammatory treatment. Hesitancy in the decision of escalating immunsuppresive treatment rather than CMV disease may be responsible for worsening disease course and increased colectomy rate in a significant number of the patients who are tissue CMV-PCR (+).

Role of Serum Proteinase 3 Antineutrophil Cytoplasmic Antibodies in the Diagnosis, Evaluation of Disease Severity, and Clinical Course of Ulcerative Colitis

Background/AimsProteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a serologic marker for granulomatosis with polyangiitis. However, recent studies have also shown their role as diagnostic markers for ulcerative colitis (UC). This study was performed to investigate the clinical roles of PR3-ANCAs in the disease severity, disease extension, and clinical course of UC.MethodsSerum PR3-ANCAs were measured in 173 UC patients including 77 patients with new-onset patients UC diagnosed within 1 month, 110 patients with Crohn’s disease, 48 patients with other intestinal diseases, and 71 healthy controls. Associations between the PR3-ANCA titer and clinical data, such as disease severity, disease extension, and clinical course, were assessed. The clinical utility of PR3-ANCA measurement was evaluated by receiver operating characteristic (ROC) analysis.ResultsPR3-ANCA ≥3.5 U/mL demonstrated 44.5% sensitivity and 95.6% specificity for the diagnosis of UC in all patients. PR3-ANCA positivity was more prevalent in the 77 new-onset UC patients (58.4%). In this group, the disease severity and extension were more severe in PR3-ANCA positive patients than in PR3-ANCA negative group (p<0.001). After treatment, the partial Mayo scores were significantly decreased with the PR3-ANCA titers. The proportion of patients who required steroids for induction therapy was significantly higher among PR3-ANCA positive than negative group. ROC analysis revealed that PR3-ANCA ≥3.5 U/mL had 75% sensitivity and 69.0% specificity for steroid requirement in new-onset UC patients.ConclusionsOur results indicate that PR3-ANCA measurement is useful not only for diagnosing UC but also for evaluating disease severity and extension and predicting the clinical course.

ABCC7/CFTR Expression Is Associated with the Clinical Course of Ulcerative Colitis Patients.

Inflammatory bowel disease includes ulcerative colitis (UC) and Crohn's disease (CD) of unknown etiology. The expression of ATP-binding cassette (ABC) family proteins has been associated with drug resistance and development of UC. The cystic fibrosis transmembrane conductance regulator (CFTR) or also known as ABCC7 is involved in the inflammatory chronic response. The aim of this study was to evaluate the role of ABCC7/CFTR in UC patients and normal controls without inflammation. This is an exploratory, observational, and cross-sectional study that included a total of 62 patients with UC and normal controls. Gene expression of CFTR was measured by RT-PCR, and protein expression of CFTR was determined by western blot analysis. We found a significant downregulation of the CFTR gene expression in patients with active UC compared to normal controls without inflammation (P < 0.004); even the gene expression of CFTR was decreased in remission UC patients compared to normal controls without inflammation (P = 0.04). The CFTR gene expression was associated with the clinical course of UC and the protein expression of CFTR was decreased in active UC patients compared to normal controls without inflammation suggesting that this molecule might play a role in the inflammation in UC patients.

Mucosa-associated gut microbiota reflects clinical course of ulcerative colitis

This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC.

Treatment and outcome of ulcerative colitis during the first 10 years after diagnosis in a prospectively followed population-based cohort

Background and aims There is a shortage of studies evaluating the effect of prevalent use of immunomodulators (IMMs) and biologicals on the clinical course of ulcerative colitis (UC) during 10 years. The aim of the present study is to report the use of drugs and surgery as well as mortality in a population based setting. Methods Between 2005 and 2009, we identified 330 patients in all ages (3–86 years) with an incident diagnosis of UC in the County of Uppsala, Sweden. They were followed prospectively and the medical notes were retrospectively analysed with special reference to the use of drugs, surgery and mortality. Results Median follow-up was 11.2 years (inter-quartile range 10.2–12.7). Out of the 330 patients, 298 (90.3%) could be followed for at least 10 years or until death. The cumulative exposure to different drugs was as follows: 5-ASA 96.6%, steroids 73.3%, IMMs 35.4% and biologicals 11.4%. Fourteen patients (4.6%) needed a colectomy during the observation time. Overall mortality in 10 years was 7% (23/330) whereof three patients died as a consequence of the disease or its treatment. Three patients (0.9%) were diagnosed with colonic cancer of whom two also had sclerosing cholangitis. Conclusions A frequent use of IMMs and biologicals during 10 years, can result in a low need for colectomy without increased mortality compared to previous reports.