June Hwa Bae, Su Hyun Park, Jung-Bin Park, Ji Eun Baek, Seung Wook Hong, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Kyeong Ok Kim, Byung Ik Jang, Mi Rae Lee, Eun Soo Kim, Sang Hyoung Park
Received April 18, 2024 Accepted July 15, 2024 Published online August 29, 2024
Background/Aims Video capsule endoscopy is rarely used to diagnose Crohn’s disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases.
Methods This multicenter study included patients with Crohn’s disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis.
Results Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn’s disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393–1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn’s disease-related hospitalization, and surgeries (log-rank test P< 0.05).
Conclusions Patients with Crohn’s disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.
Background/Aims Treatment using tumor necrosis factor-α (TNF-α) inhibitors is one of the risk factors for active tuberculosis (TB) in patients with Crohn’s disease (CD). Biologics, such as ustekinumab (UST) and vedolizumab (VDZ), are less likely to cause opportunistic infections. However, large-scale studies for active TB and biologics other than TNF-α inhibitors are limited. We aimed to investigate the association between biologics and active TB utilizing a Japanese medical claims database.
Methods We analyzed retrospectively the association of the risk of active TB development with treatment using TNF-α inhibitors and other biologics (UST and VDZ) in patients with CD using the Japanese Medical Data Vision (MDV) database between April 2008 and June 2022. The durations of each biologic and biologic-free treatment were calculated for each patient. Univariate and multivariate analyses were performed using the Cox proportional hazards model, with the utilization of biologics considered as time-dependent covariates.
Results We included 28,811 patients with CD in MDV database. Finally, 17,169 patients were analyzed. In total, 7,064 patients were categorized as biologic-naïve, while 10,105 were classified as biologic-experienced. Seventeen patients developed active TB, including 7 on infliximab, 5 on adalimumab, and 5 on no biologics. None of the patients treated with UST and VDZ developed active TB. Multivariate analysis suggested that TNF-α inhibitors were the risk factors for active TB (hazard ratio, 3.66; P= 0.020).
Conclusions TNF-α inhibitors, but not UST or VDZ, are risk factors for active TB in Japanese patients with CD.
Background/Aims Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn’s disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD.
Methods This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD.
Results Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=–0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification.
Conclusions LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.
Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
Background/Aims Crohn’s disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort.
Methods Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months.
Results A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91–11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60–21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P= 0.011).
Conclusions Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.
Nonalcoholic fatty liver disease (NAFLD) has been shown to be linked to inflammatory bowel disease (IBD) due to established risk factors such as obesity, age, and type 2 diabetes in numerous studies. However, alternative research suggests that factors related to IBD, such as disease activity, duration, and drug-induced toxicity, can contribute to NAFLD. Recent research findings suggest IBD relapses are correlated with dysbiosis, mucosal damage, and an increase in cytokines. In contrast, remission periods are characterized by reduced metabolic risk factors. There is a dichotomy evident in the associations between NAFLD and IBD during relapses and remissions. This warrants a nuanced understanding of the diverse influences on disease manifestation and progression. It is possible to provide a holistic approach to care for patients with IBD by emphasizing the interdependence between metabolic and inflammatory disorders.
Background/Aims Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn’s disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE.
Methods Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated.
Results Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 μg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 μg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman’s rank correlation coefficient ρ = 0.681, P< 0.001).
Conclusions An LRG cutoff value of 14 μg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 μg/mL may be useful in predicting the absence of SB inflammatory findings.
Background/Aims Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.
Methods This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.
Results Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).
Conclusions Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.
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Background/Aims Transabdominal ultrasonography (US) helps evaluate Crohn’s disease (CD) activity. We investigated whether the US could predict subsequent adverse outcomes for patients with CD in clinical remission.
Methods This single-center retrospective study included patients with CD in clinical remission who underwent US between April 2011 and April 2021, focusing on the predictability of subsequent adverse outcomes within 5 years. We used the US-CD, which was calculated using multiple US findings. Predictive variables were assessed using Cox proportional hazards regression analysis, and the predictive value was evaluated using receiver operating characteristic curves.
Results Seventy-three patients were included. During a median follow-up of 1,441 days (range, 41–1,825 days), 16.4% (12/73) experienced clinical relapse, 9.6% (7/73) required endoscopic balloon dilation (EBD), 58.9% (43/73) required enhanced treatment, and 20.5% (15/73) underwent surgery. In the multivariate analysis, US-CD was significantly associated with clinical relapse (P= 0.038) and the need for enhanced treatment (P= 0.005). The area under the receiver operating characteristic curve for predicting clinical relapse and the need for EBD was 0.77 and 0.81, respectively, with US-CD (cutoff value = 11), and that for requiring enhanced treatment was 0.74 with US-CD (cutoff value = 6). Patients with US-CD ≥ 11 demonstrated a significantly higher occurrence of clinical relapse (P= 0.001) and EBD (P= 0.002) within 5 years. Patients with US-CD ≥ 6 experienced a significantly higher likelihood of requiring enhanced treatment (P< 0.001) within 5 years.
Conclusions High US-CD is associated with subsequent adverse outcomes in patients with CD.
Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a nonspecific chronic inflammation of the gastrointestinal tract. Despite recent advances in therapeutics and newer management strategies, IBD largely remains untreatable. Helminth therapy is a promising alternative therapeutic for IBD that has gained some attention in the last two decades. Helminths have immunomodulatory effects and can alter the gut microbiota. The immunomodulatory effects include a strong Th2 immune response, T-regulatory cell response, and the production of regulatory cytokines. Although concrete evidence regarding the efficacy of helminth therapy in IBD is lacking, clinical studies and studies done in animal models have shown some promise. Most clinical studies have shown that helminth therapy is safe and easily tolerable. Extensive work has been done on the whipworm Trichuris, but other helminths, including Schistosoma, Trichinella, Heligmosomoides, and Ancylostoma, have also been explored for pre-clinical and animal studies. This review article summarizes the potential of helminth therapy as an alternative therapeutic or an adjuvant to the existing therapeutic procedures for IBD treatment.
Background/Aims Assessment of quality of magnetic resonance enterography (MRE) in small bowel Crohn’s disease (CD) activity evaluation has received little attention. We assessed the impact of bowel distention and motion artifact on MRE activity indices in ileal CD.
Methods A cohort of patients who underwent contemporaneous MRE and colonoscopy for ileal CD assessment between 2014 and 2021 at 2 centers were audited. An abdominal radiologist blinded to clinical data reviewed each MRE, graded bowel distention and motion artifact upon a pre-specified 3-point scale and calculated the original magnetic resonance index of activity (MaRIA) and simplified MaRIA (sMaRIA), London index and CD MRE index (CDMI). Ileal endoscopic activity was graded via the Simplified Endoscopy Score for CD (SES-CD). The performance of MRE indices in discriminating active disease (SES-CD ≥3) stratified by MRE quality was measured by receiver operator characteristic analyses.
Results One hundred and thirty-seven patients had MRE and colonoscopy within a median of 16 days (range, 0–30 days) with 63 (46%) exhibiting active disease (SES-CD ≥3). Forty-four MREs (32%) were deemed low quality due to motion artifact and/or moderate to poor distention. Low-quality MREs demonstrated reduced discriminative performance between ileal SES-CD ≥3 and MRE indices (MaRIA 0.838 vs. 0.634, sMaRIA 0.834 vs. 0.527, CDMI 0.850 vs. 0.595, London 0.748 vs. 0.511, P<0.05 for all). Individually the presence of any motion artifact markedly impacted the discriminative performance (e.g., sMaRIA area under the curve 0.544 vs. 0.814, P<0.05).
Conclusions Image quality parameters can significantly impact MRE disease activity interpretation. Quality metrics should be reported, enabling cautious interpretation in lower-quality studies.
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Results Hemoglobin, platelet count, C-reactive protein, leucine-rich alpha-2 glycoprotein (LRG), fecal calprotectin, and fecal hemoglobin all showed significant difference in those with ulcers found on BAE. LRG and fecal calprotectin showed the highest areas under the curve (0.841 and 0.853) for detecting ulcers. LRG showed a sensitivity of 78% and specificity of 80% at a cutoff value of 13 μg/mL, whereas fecal calprotectin showed a sensitivity of 91% and specificity of 67% at a cutoff value of 151 μg/g. Dual positivity for LRG and fecal calprotectin, as well as LRG and fecal hemoglobin, both predicted ulcers with an improved specificity of 92% and 100%. A positive LRG or fecal calprotectin/hemoglobin showed an improved sensitivity of 96% and 91%. Positivity for LRG and either of the fecal biomarkers was associated with increased risk of hospitalization, surgery, and relapse.
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Background/Aims Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD).
Methods Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies.
Results One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively.
Conclusions Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.
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Background/Aims The study objective is to investigate the ultrasound features that allow suspecting the presence of submucosal fat deposition, called the fat halo sign (FHS), in the intestinal wall of patients with Crohn’s disease.
Methods Computed tomography (CT) examinations over a period of 10 years were reviewed for the presence of the FHS in the bowel wall. A measurement of less than –10 Hounsfield units was regarded as indicative of fat. We included only patients who had undergone ultrasound examinations 3 months before or after CT. The study cohort group comprised 68 patients. Wall and submucosal thickness were measured on longitudinal ultrasound sections. A receiver operating characteristic curve was constructed to determine the best cutoff of ultrasound submucosal wall thickness value for predicting FHS in the bowel wall determined on CT.
Results The FHS was present in 22 patients (31%) on CT. There were significant differences between submucosal thickness of patients with FHS and patients without FHS (4.19 mm vs. 2.41 mm). From the receiver operating characteristic curve, a threshold value of 3.1 mm of submucosal thickness had the best sensitivity and specificity to suspect FHS (95.5% and 89.1%, respectively; area under the curve, 0.962), with an odds ratio of 172. All of 16 patients with a submucosal thickness >3.9 mm had FHS.
Conclusions FHS in patients with Crohn’s disease can be suspected on ultrasound in cases with marked thickening of the submucosa layer. In these cases, the activity of the disease should be measured by other parameters such as the color Doppler.
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Background/Aims The data on the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD) are conflicting. The present systematic review was thus conducted to study the prevalence of HBV and HCV markers in patients with IBD.
Methods A comprehensive literature search of 3 databases was conducted from 2000 to April 2022 for studies evaluating the prevalence of HBV or HCV in patients with IBD. Pooled prevalence rates across studies were expressed with summative statistics.
Results A total of 34 studies were included in the final analysis. The pooled prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies were 3.3% and 14.2%, respectively. In HBsAg positive IBD patients, hepatitis B e antigen positivity and detectable HBV DNA were seen in 15.3% and 61.0% of patients, respectively. Only 35.6% of the IBD patients had effective HBV vaccination. The pooled prevalence of anti-HCV and detectable HCV RNA were 1.8% and 0.8%, respectively. The pooled prevalence of markers of HBV infection was higher in Asian studies, while the prevalence of markers of HCV infection was higher in European studies. The prevalence of viral hepatitis markers was similar between IBD patients and the general population and that between ulcerative colitis and Crohn’s disease.
Conclusions The prevalence of markers of viral hepatitis remains same as the general population with significant regional variations, although the quality of evidence remains low due to publication bias. Only a small proportion of IBD patients had an effective HBV vaccination, requiring improvement in screening and vaccination practices.
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Background/Aims The inflammatory bowel disease (IBD)-disk is a validated, visual, 10-item, self-administered questionnaire used to evaluate IBD-related disability. The present study aimed to evaluate IBD-disk in assessment of IBD daily life burden and its relation with disease activity. Methods: A cross-sectional study was conducted between June 2021 and December 2021. Patients with IBD were asked to complete the IBD-disk and a visual analogue scale of IBD daily-life burden (scored from 0–10, score >5 indicative of high burden). The internal consistency of IBD-disk, correlation with IBD daily life burden and disease activity (assessed by partial Mayo score and Harvey Bradshaw Index in patients with ulcerative colitis [UC] and Crohn’s disease [CD], respectively) and diagnostic performance of IBD-disk to detect high burden were analyzed. Results: Out of the 546 patients (mean age 40.33±13.74 years, 282 [51.6%] males) who completed the IBD-disk, 464 (84.98%) had UC and the remaining (n=82, 15.02%) had CD. A total of 311 patients (291 UC and 20 CD; 56.95%) had active disease. The mean IBD-disk total score and IBD daily life burden were 18.39±15.23 and 2.45±2.02, respectively. The IBD-disk total score correlated strongly with the IBD daily life burden (ρ=0.94, P<0.001), moderately with partial Mayo score (ρ=0.50) and weakly with Harvey Bradshaw Index (ρ=0.34). The IBD-disk total score >30 predicted high IBD daily-life burden. Conclusions: The IBD-disk accurately predicts the daily life burden and parallels disease activity in patients with IBD and can be applied in clinical practice. (Intest Res, Published online)
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Intest Res 2023;21(1):43-60. Published online October 18, 2022
Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.
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Intest Res 2023;21(2):244-251. Published online August 8, 2022
Background/Aims Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes.
Methods Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients’ electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised.
Results The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863–9.021; P< 0.001) and Crohn’s disease (odds ratio, 3.552; 95% confidence interval, 1.590–7.934; P= 0.002).
Conclusions Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.
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After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn’s disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn’s primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.
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Background/Aims Abdominal aortic calcium (AAC) deposition has been suggested as a marker of early atherosclerosis. There is no published data on the evaluation of AAC in inflammatory bowel disease (IBD).
Methods AAC was quantified by computed tomography or enterography scans performed in 98 IBD patients and 1:1 age and sex matched controls. AAC deposition was correlated with IBD characteristics, disease activity or severity parameters, laboratory tests and cardiovascular disease (CVD) risk factors.
Results Moderate-severe grade of AAC was found in 35.7% of IBD patients compared to 30.6% of controls (P= 0.544). IBD with CVD and ulcerative colitis patients had significantly higher rates of more severe atherosclerotic lesions (P= 0.001 and P= 0.01, respectively). AAC deposition was similarly distributed in age groups ( < 45, 45–64, and ≥ 65 years) among patients and controls. Multivariate analysis after excluding CVD risk confounders for non-CVD patients found extensive disease (P= 0.019) and lifetime steroids (P= 0.04) as independent risk factors for AAC. Anti-tumor necrosis factor α (TNF-α) use was negatively associated with AAC deposition in non-CVD IBD patients (odds ratio, 0.023; 95% confidence interval, 0.001–0.594; P= 0.023).
Conclusions More than one-third of IBD patients have moderate to severe AAC. Better control of inflammation with anti-TNF-α agents seems to protect IBD patients from ACC deposition and subsequent atherosclerosis.
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Background/Aims Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India.
Methods A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD.
Results During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn’s disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD.
Conclusions Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.
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Kyunghwan Oh, Hee Seung Hong, Nam Seok Ham, Jungbok Lee, Sang Hyoung Park, Suk-Kyun Yang, Hyuk Yoon, You Sun Kim, Chang Hwan Choi, Byong Duk Ye, on behalf of the Korean Association for the Study of Intestinal Diseases
Intest Res 2023;21(1):137-147. Published online July 12, 2022
Background/Aims We investigated the real-world effectiveness and safety of ustekinumab (UST) as induction treatment for Koreans with Crohn’s disease (CD).
Methods CD patients who started UST were prospectively enrolled from 4 hospitals in Korea. All enrolled patients received intravenous UST infusion at week 0 and subcutaneous UST injection at week 8. Clinical outcomes were assessed using Crohn’s Disease Activity Index (CDAI) scores at weeks 8 and 20 among patients with active disease (CDAI ≥150) at baseline. Clinical remission was defined as a CDAI <150, and clinical response was defined as a reduction in CDAI ≥70 points from baseline. Safety and factors associated with clinical remission at week 20 were also analyzed.
Results Sixty-five patients were enrolled between January 2019 and December 2020. Among 49 patients with active disease at baseline (CDAI ≥150), clinical remission and clinical response at week 8 were achieved in 26 (53.1%) and 30 (61.2%) patients, respectively. At week 20, 27 (55.1%) and 35 (71.4%) patients achieved clinical remission and clinical response, respectively. Twenty-seven patients (41.5%) experienced adverse events, with serious adverse events in 3 patients (4.6%). One patient (1.5%) stopped UST therapy due to poor response. Underweight (body mass index <18.5 kg/m2) (odds ratio [OR], 0.085; 95% confidence interval [CI], 0.014–0.498; P=0.006) and elevated C-reactive protein at baseline (OR, 0.133; 95% CI, 0.022–0.823; P=0.030) were inversely associated with clinical remission at week 20.
Conclusions UST was effective and well-tolerated as induction therapy for Korean patients with CD.
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Background/Aims Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same.
Methods Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL.
Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy.
Results Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17.
Conclusions In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.
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Background/Aims Fecal S100A12 (FS) and serum S100A12 (SS) have been reported as novel biomarkers that accurately reflect intestinal inflammation. We evaluated if FS and SS in comparison to fecal calprotectin (FC) are associated with poor future outcomes in clinically quiescent Crohn’s disease (CD) patients.
Methods We prospectively enrolled 49 CD patients in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150 for the past 6 months). Patients were followed for a median period of 4.4 years (interquartile range [IQR], 4.3–4.5). The following outcomes were evaluated: clinical relapse, CD-related hospitalization, step-up of medical treatment, and CD-related intestinal resection. Cox proportional-hazard regression model was constructed to assess the association of baseline markers with time-to-event outcomes.
Results The median levels of baseline FS, FC, and SS were 0.042 mg/kg (IQR, 0.005–0.179), 486.8 mg/kg (IQR, 203.5–886.8) and 1,398.2 ng/mL (IQR, 791.8–2,759.9), respectively. FS correlated with FC (r = 0.689), erythrocyte sedimentation rate (r = 0.524), C-reactive protein (r = 0.499), and albumin (r = –0.446), but not with CDAI (r = 0.045). Interestingly, increased FS (top quartile) was associated with a 4.9-fold increased rate of future CD-related hospitalization (P= 0.009) and a 2.8-fold increased rate of step-up of medical treatment (P= 0.032), whereas increased FC and SS were not. These findings remained significant after adjusting for age, sex, disease duration, current smoking, C-reactive protein, serum albumin, CDAI, and FC, individually.
Conclusions In this pilot study, increased FS and not FC or SS, was significantly associated with increased rates of future CD-related hospitalization and step-up of medical treatment among CD patients in clinical remission.
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Background/Aims Although anti-tumor necrosis factor (TNF)-α agents are important therapeutic drugs for Crohn’s disease (CD), data regarding their long-term sustained effects are limited. Herein, we evaluated the long-term loss of response (LOR) to anti-TNF-α agents in patients with CD.
Methods This retrospective study included patients with CD who started treatment with infliximab or adalimumab as a first-line therapeutic approach. The cumulative event-free, retention, and surgery-free rates after the start of biological therapy were analyzed. Secondary LOR was analyzed in patients who achieved corticosteroid-free clinical remission after the start of biological therapy. Cox proportional hazards models were used to analyze the predictive factors of secondary LOR.
Results The cumulative event-free rates at 1, 2, 5, and 10 years were 83.3%, 75.1%, 37.4%, and 23.3%, respectively. The incidence of LOR was 10.6% per patient-year of follow-up. At 12–14 weeks after the start of biological therapy, the proportion of patients with a C-reactive protein to albumin (CRP/ALB) ratio ≥0.18 was significantly higher in patients with LOR (P<0.001). Multivariate analysis indicates that a CRP/ALB ratio ≥0.18 (hazard ratio [HR], 5.86; 95% confidence interval [CI], 1.56–22.0; P=0.009) and upper gastrointestinal tract inflammation (HR, 3.00; 95% CI, 1.26–7.13; P=0.013) were predictive factors of secondary LOR.
Conclusions Although anti-TNF-α agents contributed to long-term clinical remission of CD, the annual incidence of secondary LOR was 10.6%. The CRP/ALB ratio at 3 months after the start of biological therapy and upper gastrointestinal tract inflammation were identified as predictive factors of secondary LOR.
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Intest Res 2022;20(3):361-369. Published online March 15, 2022
Background/Aims Tight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn’s disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD.
Methods Patients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used.
Results One hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P<0.001); the area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.70–0.88; P<0.001). The FC value that best reflected the activity in IUS was 100 μg/g with sensitivity, specificity, and positive and negative predictive values of 73.0%, 71.4%, 79.3% and 63.8%, respectively. There were no differences in FC concentration between patients with or without transmural complications. The addition of serum C-reactive protein to FC did not improve the ability to assess IUS activity.
Conclusions FC has a significant correlation with IUS to monitor ileal CD activity. This correlation is weak and it does not allow assessing the presence of CD complications. Both tests should be used in conjunction for tight control of ileal CD. More studies on noninvasive tests in this location are needed.
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Background/Aims Epidemiological data on steroid use in South Korean patients with inflammatory bowel disease (IBD) are limited. We documented the steroid use patterns in these patients, and whether physician education on appropriate steroid use affected these patterns.
Methods ACTION was an observational cohort study conducted in adults (≥19 years) with IBD. A retrospective chart review was performed at baseline (cohort 1) and 1 year after physician training (cohort 2). Eligible cases with excessive or inappropriate steroid use were identified, along with any associated risk factors.
Results Data were collected during May 2018-July 2019 from patients with Crohn’s disease (CD) and ulcerative colitis (UC) in cohort 1 (n=1,685) and cohort 2 (n=1,649). At baseline, 155 patients (9.2%) had received steroids within the previous 12 months, 46 (29.7%) of whom had used steroids excessively, 16 (34.8%) of these having inappropriately used excessive steroids. Although steroid exposure was similar in cohort 1 (9.2%) and cohort 2 (9.7%), the latter comprised fewer excessive steroid users (20.0% vs. 29.7%). Severe disease was associated with excessive steroid use in cases with UC, but not with CD.
Conclusions Although, overall steroid use was relatively low in South Korean patients with IBD, one-third of steroid users used them excessively, and one-third among these used excessive steroids inappropriately. High disease activity was the main risk factor for excessive steroid use which may potentially be reduced by physician education, especially in cases with UC. Active screening to minimize excessive and inappropriate steroid use through physician education should be considered.
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Methods A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.
Results A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%).
Conclusions In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.
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