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Crohn’s disease (CD) is an idiopathic inflammatory bowel disease involving the small and/or large intestine. More than 50% of Western CD patients and up to 88% of Asian CD patients may have small intestinal involvement. Video capsule endoscopy (VCE) has a higher diagnostic yield than small bowel barium radiography and computed tomography enterography for the detection of small intestinal involvement of CD. VCE also provides diagnostic yields comparable to magnetic resonance- (MR-) based enterography or enteroclysis and may have several advantages over MR-based tests for the detection of early small intestinal lesions. Several studies have suggested the use of VCE-based disease activity scoring systems to evaluate small intestinal mucosal disease activity, although their clinical relevance needs to be further studied. A possible indication for VCE is recurrence monitoring after complete surgical excision of CD-involved segments but its usefulness and efficacy compared with conventional endoscopy should be evaluated. The capsule retention rate ranges from 0 to 5.4% in suspected CD patients and from 0 to 13.2% in established CD patients. If VCE is necessary, significant small bowel stricture should be ruled out before VCE by performing a patency capsule study and/or small bowel radiological study in suspected or established CD patients. [ABSTRACT FROM AUTHOR]

Fecal calprotectin (FC) is commonly used to assess Crohn's disease (CD) activity. However, standardized cut-off values accounting for bowel resection history and disease location are lacking. In this study, we analyzed data from patients with CD who underwent magnetic resonance enterography, ileocolonoscopy, and FC measurements from January 2017 to December 2018. In 267 cases from 254 patients, the FC levels in the 'operated' patients were higher when the disease was active compared with those who were in the remission group (178 vs. 54.7 μg/g; p < 0.001), and similar findings were obtained for the 'non-operated' patients (449.5 vs. 40.95 μg/g; p < 0.001). The FC levels differed significantly according to the location of inflammation, with lower levels in the small bowel compared to those in the colon. The FC cut-off levels of 70.8 μg/g and 142.0 μg/g were considered optimal for predicting active disease for operated and non-operated patients, respectively. The corresponding FC cut-off levels of 70.8 μg/g and 65.0 μg/g were observed for patients with disease only in the small bowel. In conclusion, different FC cut-off values would be applicable to patients with CD based on their bowel resection history and disease location. Tight control with a lower FC target may benefit those with a history of bowel resection or small-bowel-only disease. [ABSTRACT FROM AUTHOR]

Background and Aims: Reduced body muscle mass is a poor prognostic factor for inflammatory bowel disease (IBD). In this study, we investigated the prevalence of sarcopenia at diagnosis and its clinical significance in Korean patients with IBD. Methods: The prevalence of sarcopenia in IBD patients between June 1989 and December 2016 was investigated using a well-characterized referral center-based cohort. Abdominopelvic computed tomography within six months from IBD diagnosis was used for the evaluation. Sarcopenia was defined as an L3 skeletal muscle index of < 49 cm2/m2 for male and < 31 cm2/m2 for female. The clinical characteristics and outcomes were evaluated with respect to sarcopenia. Results: A total of 1,027 patients (854 Crohn's disease [CD]; 173 ulcerative colitis [UC]) were evaluated. Sarcopenia was found in 56.8% of the population (CD, 57.5%; UC, 53.2%), and male were more likely to be sarcopenic (CD, 94.3%; UC, 91.6%). There were no significant differences in the cumulative risk of using steroids, immunomodulators, biologics, and bowel resections (or colectomy) with or without sarcopenia during follow-up (median: CD, 5.8 years; UC, 3.7 years). In sarcopenic patients with CD, there was a significantly higher cumulative risk of perianal surgeries than in non-sarcopenic patients with CD (Log-rank test; P = 0.001). However, the risk of perianal surgeries was not significant in multivariate analysis (Odds ratio 1.368; 95% confidence interval 0.782–2.391; P = 0.272). Conclusion: Sarcopenia at diagnosis may have no significant prognostic value for medical treatment and bowel resection, but it may be associated with perianal CD. [ABSTRACT FROM AUTHOR]

Background: Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment.Methods: The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn's disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group.Results: Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014-1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262-3.066, p = 0.862).Conclusions: In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy. [ABSTRACT FROM AUTHOR]

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn's disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn's disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX (p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration. [ABSTRACT FROM AUTHOR]

Background: The Rutgeerts score is used to predict postoperative recurrence in CD patients after ileocolic resection and is primarily based on endoscopic findings at the neoterminal ileum. However, the optimal assessment of anastomotic ulcers (AUs) remains subject to debate. Aims: We aimed to investigate the association between anastomotic ulcers (AUs) and endoscopic recurrence in postoperative Crohn's disease (CD) patients. Methods: This single-center retrospective study, conducted between 2000 and 2016, evaluated postoperative CD patients with endoscopic remission at the first ileocolonoscopy within 1 year after ileocolic resection and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs in predicting endoscopic recurrence. Results: Among 116 patients who were in endoscopic remission defined as the RS of i0 to i1 at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the median 30.0 months (interquartile range, 21.3–53.3) of follow-up after the first ileocolonoscopy, 56.1% (55/98) of patients showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs, defined as either an ulcer occupying ≥ 1/4 of the circumference, ≥ 3 ulcers confined to anastomotic ring, or any ulcers extending to the ileocolonic mucosa, showed endoscopic recurrence. On multivariable analysis, AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87–10.0; P < 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95–79; P < 0.001) were associated with endoscopic recurrence. Conclusions: AUs are associated with a significantly high risk of endoscopic recurrence in postoperative CD patients who are in endoscopic remission. [ABSTRACT FROM AUTHOR]

Background and Aim: Acute severe lower gastrointestinal bleeding (LGIB) in patients with Crohn's disease (CD) is uncommon; however, it is a potentially life‐threatening complication, and its recurrence is common. We thus aimed to identify the predictors for rebleeding in CD patients with acute severe LGIB and particularly focused on whether anti‐tumor necrosis factor (TNF) therapy lowers the risk of rebleeding compared with conventional medical therapy (CMT) or surgery. Methods: The risk of rebleeding was analyzed in 131 CD patients with acute severe LGIB. Patients were classified into the CMT group (n = 99), anti‐TNF therapy group (n = 22), and surgery group (n = 10). No patients in the surgery group received anti‐TNF therapy. Results: During the median follow‐up of 98 months after the first episode of acute severe LGIB, rebleeding occurred in 50.5%, 18.2%, and 30.0% of the CMT group, anti‐TNF therapy group, and surgery group, respectively (P = 0.015). The cumulative risks of rebleeding at 1 and 10 years were 20.0% and 64.7% in the CMT group, 13.6% and 18.4% in the anti‐TNF therapy group, and 0% and 40.7% in the surgery group, respectively (P = 0.020). Multivariable Cox regression analysis showed that anti‐TNF therapy was associated with a lower risk of rebleeding compared with CMT (hazard ratio, 0.303; 95% confidence interval, 0.108–0.849; P = 0.023). Conclusions: In CD patients with acute severe LGIB, anti‐TNF therapy may reduce the risk of rebleeding compared with CMT. Although surgery is considered effective in preventing early rebleeding, concomitant anti‐TNF therapy may be helpful in further lowering the long‐term risk of rebleeding. [ABSTRACT FROM AUTHOR]

Background and Aim: The clinical impact of perianal Crohn's disease (CD) (pCD), a well‐known poor prognostic factor of CD, has not been fully evaluated in Asian patients. We investigated the outcomes of CD in Korean patients according to the presence of pCD at CD diagnosis. Methods: Using 2010–2014 data from the national health insurance claims database, we evaluated the disease course of CD according to the presence of pCD at CD diagnosis. The results were verified in a hospital‐based cohort of 2923 patients. Results: The cumulative risk of intestinal resection was lower in patients with pCD at diagnosis than in those without, in the population‐based cohort (9.1% vs 14.7% at 5 years after diagnosis, P < 0.001), but it was similar between the two groups in the hospital‐based cohort (36.8% vs 36.8% at 10 years after diagnosis, P = 0.950). Moreover, the cumulative risk of behavioral progression was not significantly different between the two groups in the hospital‐based cohort (43.4% vs 41.6% at 10 years after diagnosis, P = 0.366). On multivariable analysis, pCD at CD diagnosis was not a predictor of intestinal resection, behavioral progression, CD‐related hospital admission, or diverting surgery; however, it was an independent predictor of proctectomy (hazard ratio [HR] 3.210, P < 0.001) and anorectal cancer (HR 3.104, P = 0.047). Conclusions: Although the presence of pCD increased the risk of proctectomy and anorectal cancer in Asian patients, the clinical impact of pCD on the overall outcomes of patients with CD may be less significant in Asian patients compared with Western patients. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown vitamin D status to be associated with disease activity in patients with inflammatory bowel disease (IBD), but its influence on the clinical course of IBD has not been established. Aims: We aimed to analyze whether the serum 25-hydroxyvitamin D3 [25(OH)D] status is associated with clinical characteristics and affects the risk of surgery in patients with IBD. Methods: From the IBD registry of the Asan Medical Center, we identified all patients who had at least one 25(OH)D measurement; we then analyzed the association between clinical factors and 25(OH)D status. 25(OH)D was considered borderline deficient, deficient, and severely deficient at levels of < 30, < 20, and < 10 ng/mL, respectively. Results: We included 711 Crohn's disease (CD) and 764 ulcerative colitis (UC) patients who had not undergone surgery before 25(OH)D was measured. Both in CD and in UC patients, reduced 25(OH)D was associated with higher disease activity scores and CRP levels (p < 0.001). Severe 25(OH)D deficiency was associated with ileocolonic disease and complicated behavior in CD (p < 0.05) and was relevant to the disease extent in UC (p < 0.001). Additionally, severe 25(OH)D deficiency was associated with CMV colitis in patients with UC (p < 0.001). In multivariable analysis, severe deficiency of 25(OH)D was an independent risk factor for surgery in both CD (HR 1.93, 95% confidence interval [CI] 1.38–2.70) and UC (HR 2.77, 95% CI 1.14–6.74). Conclusion: Severe 25(OH)D deficiency may be a marker of a more aggressive clinical course of IBD. [ABSTRACT FROM AUTHOR]

Introduction: Immunomodulators remain fundamental for the medical treatment of Crohn's disease (CD). Methotrexate (MTX) is widely used as a second-line immunomodulator; however, there is a lack of recent data on MTX monotherapy among the Asian population with CD. Therefore, in this study, we aimed to investigate the tolerability and clinical outcomes of MTX in Korean patients with CD. Methods: A retrospective chart review was performed for CD patients treated with MTX monotherapy or in combination with 5-aminosalicylic acid (5-ASA), at the Asan Medical Center, Seoul, South Korea. The tolerability of MTX monotherapy within 6 months was assessed and the clinical effectiveness of MTX was evaluated based on the Crohn's disease activity index (CDAI). Results: In total, 85 patients were included, of which 29 (34.1%) discontinued MTX due to intolerability during the follow-up. Adverse events (AEs) were reported in 41 (48.2%) patients. The most common AE was gastrointestinal disorders (17/41) and only one patient experienced a serious AE, a systemic infection that required hospitalization. Among the 56 patients who tolerated MTX within 6 months, 44 (65.9%) showed a clinical response. Moreover, no factor was significantly associated with intolerability. The administration method was the only factor significantly associated with a response to MTX (p = 0.041). The adjusted odds ratio of parenteral injection compared to oral administration was 5.68 (95% confidence interval (CI), 1.07–30.08). Conclusion: In this study, one-third of patients were intolerant to MTX; nonetheless, the response rate was as high as 65.9% among tolerant patients. In addition, no significant factors affected intolerability. In terms of the clinical response, parenteral injection could be better than oral administration. [ABSTRACT FROM AUTHOR]

Background and Aims: The phenotypic concordance among familial cases of inflammatory bowel disease (IBD) has been rarely reported. Thus, the present study aimed to evaluate the concordance regarding disease type and phenotypic features in a large cohort of Korean patients with IBD. Methods: A total of 6647 patients with IBD who visited the Asan Medical Center between June 1989 and September 2016 were enrolled in the study. When at least two familial cases existed in our cohort, they were included in the concordance analysis (κ index). The concordance between younger and older members for IBD type [Crohn's disease (CD) and ulcerative colitis (UC)] and phenotypic characteristics such as disease extent and location, disease behavior, the use of medication, and need for surgery were evaluated. Results: A positive family history of IBD was noted in 216 patients with CD (7.0%) and in 238 patients with UC (6.7%). Of all patients, 167 consanguineous pairs in 146 families were identified. The crude concordance rate for IBD type was 82.6% with a κ index of 0.656 [95% confidence interval (CI): 0.545–0.768, good concordance]. There was mild concordance for disease location in CD (κ = 0.256; 95% CI: 0.007–0.505) and for the use of antitumor necrosis factor agents in UC (κ = 0.354; 95% CI: −0.049–0.757). The concordance for IBD type and several phenotypes in first‐degree relative pairs was better than that in the entire pairs. Conclusions: Disease type and phenotypic characteristics of patients with familial IBD may be anticipated. [ABSTRACT FROM AUTHOR]

Background: Little is known about the natural history of perianal fistulas in Asian populations with Crohn's disease (CD).Aims: We investigated the incidence and outcomes of perianal CD (pCD) in Korean CD patients.Methods: A nationwide population-based cohort of 6265 CD patients diagnosed in 2010-2014 was analyzed to investigate the incidence and outcomes of pCD. The results were validated in a hospital-based cohort of 2923 CD patients diagnosed in 1981-2015. Factors associated with pCD development were analyzed. The incidence and outcomes of pCD were compared between the prebiologic and biologic eras.Results: pCD occurred in 39.2% of the population-based cohort and 56.1% of the hospital-based cohort during the median follow-up of 4.2 and 8.5 years, respectively. The cumulative incidence of pCD was 40.0% at 5 years after CD diagnosis in the population-based cohort and 62.5% at 20 years in the hospital-based cohort. In multivariate analysis, pCD development was positively associated with male sex, younger age and colonic involvement at diagnosis, early diagnosis, and CD diagnosis in the prebiologic era. The cumulative probability of proctectomy at 10, 20, and 30 years after pCD diagnosis was 2.9%, 12.2%, and 16.2%, respectively. The cumulative incidence of pCD occurring after CD diagnosis and the cumulative probability of proctectomy were significantly lower in the biologic era than in the prebiologic era (p < 0.001 and p = 0.03, respectively).Conclusions: Compared with Western patients with CD, Korean patients show a high incidence of pCD but have a low probability of proctectomy, suggesting the favorable course of pCD. [ABSTRACT FROM AUTHOR]

Background and Aim: Little is known whether routine prophylaxis against Pneumocystis jirovecii pneumonia (PJP) is needed in patients with inflammatory bowel disease (IBD) on immunosuppression, especially in Asian populations. We, therefore, sought to investigate the incidence and risk factors of PJP in patients with IBD in Korea. Methods: We investigated the incidence of PJP in patients with IBD and compared the characteristics of IBD patients with PJP episodes (IBD‐PJP group) with those of matched controls (IBD‐only group) using a large, well‐characterized referral center‐based cohort. Results: Among the 6803 IBD patients (3171 with Crohn's disease and 3632 with ulcerative colitis) enrolled in the Asan IBD Registry between June 1989 and December 2016, six patients (0.09%) were diagnosed with PJP. During the 57 776.0 patient‐years of follow‐up (median 7.2 years per patient), the incidence of PJP was 10.4 cases per 100 000 person‐years, and none of these patients had received PJP prophylaxis. In case–control analysis, the IBD‐PJP group (n = 6) showed significantly higher C‐reactive protein level at diagnosis of IBD (P = 0.006), as well as higher exposure to corticosteroids (P = 0.017), than did controls (n = 24). In addition, the IBD‐PJP group showed higher rates of double (50% vs 12.5%) or triple (33.3% vs 4.2%) immunosuppression than did controls, although these are not statistically significant. Conclusions: Although the incidence of PJP in Korean patients with IBD is low, careful monitoring is necessary for the early detection of PJP. In addition to the patients receiving double or triple immunosuppression, PJP prophylaxis should be considered especially in patients with severe disease activities requiring corticosteroids. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the clinical characteristics and clinical course of Asian elderly-onset Crohn’s disease (EOCD) patients in a large well-defined cohort of South Korean IBD patients. Materials and methods: From the Asan inflammatory bowel disease registry, we identified 29 EOCD patients (diagnosed with CD in age of 60 years or over) out of 2989 CD patients (1.0%). After excluding two patients with unclear data, 27 EOCD were matched with 108 young-onset CD (YOCD) and 108 middle age-onset CD (MOCD) for the interval from symptom onset to diagnosis (±3 years) and follow-up duration (±3 years). Results: Females were predominant in the EOCD group (59.3%) compared to MOCD (31.5%) and YOCD (29.6%) groups (p = .012). In EOCD group, terminal ileal location was the most common (63.0%) at diagnosis, whereas ileocolonic location in other groups (57.4% in MOCD and 78.7% in YOCD, respectively) (p < .001). Patients with perianal fistula at CD diagnosis were less common (14.8% in EOCD vs. 28.7% in MOCD vs. 49.1% in YOCD, p < .001). During follow-up, thiopurines were used less frequently in the EOCD group (48.1% in EOCD vs. 87.0% in MOCD vs. 89.8% in YOCD, p < .001), but the risk for intestinal resection was comparable among three groups (p = .583). Conclusions: EOCD may have a better clinical course than MOCD and YOCD, as demonstrated by the similar risk for intestinal resection despite the less frequent use of thiopurines. [ABSTRACT FROM AUTHOR]

Background and Aim Smoking cessation is known to improve the course of Crohn's disease (CD). However, the factors associated with smoking cessation after CD diagnosis have not been well established. Methods Clinical characteristics and change in smoking status were evaluated in 445 current smokers at the time of CD diagnosis. Patients were classified into three subgroups based on their final smoking status and time of smoking cessation: non-quitters, quitters at diagnosis, and quitters during follow-up. Results The overall smoking cessation rate was 55.7% (248 of 445 patients). The diagnosis of CD was the main reason for quitting (41.5%, 103 of 248 patients). Smoking cessation at the time of CD diagnosis was associated with intestinal resection within 3 months from CD diagnosis (odds ratio [OR] 2.355, 95% confidence interval [CI] 1.348-4.116, P = 0.003), light smoking (OR 2.041, 95% CI 1.157-3.602, P = 0.014), and initiation of smoking before 18 years of age (OR 0.570, 95% CI 0.327-0.994, P = 0.047). Light smoking (OR 1.762, 95% CI 1.019-3.144, P = 0.043) and initiation of smoking before 18 years (OR 0.588, 95% CI 0.381-0.908, P = 0.017) were also associated with overall smoking cessation. Conclusion Quitters after CD diagnosis, including quitters at diagnosis and quitters during follow-up, had features distinct from those of non-quitters. Given the motivation at CD diagnosis, a detailed history of smoking habits should be taken and all current smokers should be encouraged to quit smoking at the time of CD diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aims: Large-scale studies regarding the long-term outcomes of adalimumab (ADA) treatment in Asian patients with Crohn's disease (CD) are still scarce.Methods: We retrospectively analyzed the long-term outcomes of ADA treatment in Korean CD patients who commenced on scheduled ADA treatment at Asan Medical Center between November 2008 and July 2016. Clinical response was defined as maintaining ADA treatment without dose intensification (DI) and/or major abdominal surgery (MAS).Results: Of the 254 patients who received at least two doses of ADA at 2-week intervals as induction therapy, 250 patients (98.4%) showed an initial favorable response by week 4. Among responders, 243 patients were followed up for longer than 4 weeks and were included for further analysis. The median duration of ADA maintenance therapy was 19.4 months. At the last follow-up, 45 patients (18.5%) required DI after a median of 16.8 months and 31 (12.8%) required MAS after a median of 8.9 months. Finally, 161 patients (66.3%) were still receiving ADA without DI and/or MAS. The cumulative probability of maintaining ADA without DI and/or MAS was 81.1% at 1 year, and 36.5% at 5 years. Secondary loss of response to previous infliximab (P = 0.001) and elevated baseline C-reactive protein at starting ADA treatment (P = 0.008) were identified as independent predictors of a poor response to ADA treatment using multivariate regression analysis.Conclusions: The long-term outcome of ADA treatment in a real-life cohort of Korean patients with CD appears to be comparable to that reported in previously published Western studies. [ABSTRACT FROM AUTHOR]

Intestinal inflammation and mucosal damage in Crohn’s disease (CD) are believed to progress even during clinical remission. We investigated the long-term prognosis of CD patients in clinical remission according to serum C-reactive protein (CRP) levels. This study included 339 CD patients in clinical remission (Crohn’s disease activity index < 150) for more than 6 months between January 2008 and December 2010. Clinical outcomes were compared between patients with normal and elevated CRP levels during clinical remission. During clinical remission, 150 patients had normal CRP consistently and 189 had elevated CRP at least once. During follow-up (median, 7.9 years [interquartile range, 6.8–8.0]), the Kaplan–Meier analysis with the log-rank test showed that normal CRP group had a longer CD-related hospitalization-free survival (P = 0.007) and a longer CD-related intestinal resection-free survival (P = 0.046) than elevated CRP group. In multivariate analysis, elevated CRP was significantly and independently associated with an increased risk of subsequent CD-related hospitalization (adjusted hazard ratio [aHR] 1.787, 95% confidence interval [CI]: 1.245–2.565, P = 0.002) and of subsequent CD-related intestinal resection (aHR 1.726, 95% CI: 1.003–2.969, P = 0.049). The most common reason for CD-related hospitalization was penetrating complications (35.6%). Even when CD patients are in clinical remission, elevated CRP is significantly associated with subsequent CD-related hospitalization and CD-related intestinal resection during follow-up. CD patients in clinical remission but elevated CRP should receive more careful attention and timely interventions to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Incidence of and risk factors for intestinal free perforation (FP) in patients with Crohn's disease (CD) are not established.Aim: To establish rate of and risk factors for FP in a large cohort of CD patients.Methods: Medical records of CD patients who visited Asan Medical Center from June 1989 to December 2012 were reviewed. After matching the FP patients to controls (1:4) by gender, year, and age at CD diagnosis, and disease location, their clinical characteristics were compared using conditional logistic regression analysis.Results: Among 2043 patients who were included in our study cohort, 44 patients (2.15%) developed FP over a median follow-up period of 79.8 months (interquartile range 37.3-124.6), with an incidence of 3.18 per 1000 person-years [95% confidence interval (CI) 2.37-4.28]. All 44 patients underwent emergency surgery, and eight patients underwent reoperation within 12 months (8/44, 18.2%). Multivariable-adjusted analysis revealed that anti-TNF therapy [odds ratio (OR), 3.73; 95% CI 1.19-11.69; p = 0.024] was associated with an increased risk of FP.Conclusions: The incidence of FP in a large cohort of Korean CD patients was 2.15%, which was similar to that in Western reports. Anti-TNF therapy could be risk factors for FP. [ABSTRACT FROM AUTHOR]

Although early treatment of Crohn’s disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed. Patients were classified into those who started anti-TNFs, or IMs but not anti-TNFs, within 2 years of diagnosis, and those who started anti-TNFs and/or IMs later. Their probabilities of intestinal surgery and intestinal complications were compared. A total of 670 patients were enrolled, 79 in the early anti-TNF, 286 in the early IM, and 305 in the late treatment group. Kaplan-Meier analysis with the log-rank test showed that from starting anti-TNFs/IMs, times to intestinal surgery (P < 0.001), stricturing complications (P = 0.002), and penetrating complications (P < 0.001) were significantly longer in the early anti-TNF/IM groups than in the late treatment group. Multivariate Cox regression analysis showed that, from starting anti-TNFs/IMs, late anti-TNF/IM treatment was independently associated with higher risks of intestinal surgery (adjusted hazard ratio [aHR] 2.321, 95% confidence interval [CI] 1.503–3.584, P < 0.001), behavioral progression (aHR 2.001, 95% CI 1.449–2.763, P < 0.001), stricturing complications (aHR 1.736, 95% CI 1.209–2.493, P = 0.003), and penetrating complications (aHR 3.315, 95% CI 2.094–5.249, P < 0.001) than early treatment. In conclusion, treatment of Asian CD patients having poor prognostic factors with anti-TNFs/IMs within 2 years of diagnosis is associated with better clinical outcomes than later treatment. [ABSTRACT FROM AUTHOR]

Background and Aim Limited data are available regarding mortality from inflammatory bowel disease in non-Caucasian populations. Herein, we evaluated overall and cause-specific mortality in a hospital-based cohort of Korean inflammatory bowel disease patients. Methods We determined mortality in 2414 Crohn's disease patients and 2798 ulcerative colitis patients diagnosed between 1977 and 2013. Standardized mortality ratios were calculated in several demographic and phenotypic subgroups. Results During the mean 9-year follow up, 114 patients died: 35 with Crohn's disease and 79 with ulcerative colitis. The overall standardized mortality ratios were 1.40 (95% confidence interval: 0.97-1.94) in Crohn's disease and 0.73 (0.58-0.91) in ulcerative colitis. In Crohn's disease, female sex, age < 30 years at diagnosis, disease duration > 10 years, ileocolonic disease at diagnosis, perianal fistula, intestinal resection, and ever-use of corticosteroids were associated with higher mortality. In ulcerative colitis, male sex, age ≥ 30 years at diagnosis, disease duration ≤ 5 years, proctitis at diagnosis, and no history of colectomy were associated with lower mortality, while primary sclerosing cholangitis was associated with higher mortality. In both Crohn's disease and ulcerative colitis, high mortality rates due to nonmalignant gastrointestinal causes (standardized mortality ratios: 4.59 and 2.32, respectively) and gastrointestinal malignancies (standardized mortality ratios: 16.59 and 3.45, respectively) were observed. Cardiovascular mortality was lower in ulcerative colitis (standardized mortality ratio: 0.47). Conclusions The overall mortality tended to be higher in Crohn's disease patients than in the general population; it was slightly lower in ulcerative colitis patients than in the general population. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) has been known to complicate Crohn’s disease (CD). Several reports in Western population revealed that CRC in CD were characterized by much younger onset and equal distribution of tumors along the entire colon. However, clinicopathologic features of CD-associated CRC in Korean population have not been well documented yet. Methods Among 2968 Korean CD patients, 16 patients (0.54%) were found to develop CRC during follow up. We reviewed clinicopathologic features of the 16 CRC patients. Results The mean age at the time of CRC diagnosis was 39.3 years (range 18–59 years) and 14 of the 16 CRCs (87.5%) occurred in anorectal region. Mucinous adenocarcinoma was strikingly frequent (9/16, 56.3%) and eight cases (8/9) of the mucinous adenocarcinoma cases were located at anorectal area. The other cases consisted of 4 tubular adenocarcinomas, 2 signet ring cell carcinomas and 1 neuroendocrine tumor. Thirteen patients (81.3%) had a history of perianal fistula and 8 of them had a histological association between the CRC and the perianal fistula. Conclusions CD-associated CRC was characterized by young age at diagnosis, mucinous histology and association with perianal fistula in Korean patients. [ABSTRACT FROM AUTHOR]

Background and Aims: To date, no large-scale studies have evaluated long-term outcomes of infliximab (IFX) treatment in Korean patients with Crohn's disease (CD).Methods: We analyzed long-term clinical responses to IFX in 582 Korean CD patients who received scheduled IFX treatments at Asan Medical Center. Clinical responses were defined as maintaining IFX without major abdominal surgery (MAS) or dose intensification.Results: Between February 2002 and July 2015, a total of 11,990 IFX infusions were administered to 582 Korean patients with CD over a median period of 36 months. At the end of follow-up, 316 (54.3 %) were still receiving IFX without MAS (71 patients, 12.2 %) or dose intensification (86 patients, 14.8 %). IFX was stopped in 109 (18.7 %) patients because of a loss of response (48 patients, 8.2 %), adverse events (30 patients, 5.2 %), or patient preferences or problems with reimbursement (31 patients, 5.3 %). The cumulative survival for maintenance of IFX without MAS or dose intensification was 89.0, 75.9, 68.3, and 50.8 % at 1, 2, 3, and 5 years, respectively. Multivariate regression analysis identified older age at the initiation of IFX (≥40 years, P = 0.006) and a longer disease duration (≥3 years, P = 0.020) as independent positive predictors of a poorer response to IFX.Conclusions: The long-term efficacy of IFX in a large, real-life cohort of Korean patients with CD appears to be similar to that in previously published Western studies. Our findings support the early use of IFX to obtain better clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Few studies have been conducted on the progression of mild Crohn's disease (CD). We aimed to investigate the natural course in mild CD patients with or without bowel damage, to identify predictors of bowel resection and to calculate the requirement for rescue medication. Methods: A total of 104 patients with mild activity (150 < CDAI < 220) with or without bowel damage were identified from among 1050 CD patients between January 2008 and May 2014. Univariate and multivariate analysis was used to identify factors associated with bowel resection. The cumulative probabilities of bowel resection and rescue medication such as steroids or anti-TNF agents were calculated. Results: The median follow-up duration was 28.2 months (IQR 26.7). Cumulative probabilities of bowel resection were 0.2, 11.8 and 42.4 % at 1, 3 and 5 years respectively. The CD patients with bowel damage had a higher bowel resection rate than those without bowel damage ( P < 0.001). The cumulative probabilities of corticosteroid-requirement were 3.0, 19.6 and 78.4 % of patients at 1, 3 and 5 years, respectively, and 2.1, 11.9 and 56.1 %, in terms of the cumulative probabilities of requiring anti-TNF agents. Patients with elevated CRP (>1.6 mg/dL) were more likely to undergo bowel resection ( P = 0.032). Conclusions: Even in CD patients with mild disease activity, the cumulative probability of bowel resection is not low if they have bowel damage or elevated CRP at baseline. Mild CD patients with bowel damage or elevated CRP at baseline need special attention. [ABSTRACT FROM AUTHOR]

BackgroundThe impact of genetic variation in thethiopurine S-methyltransferase (TPMT)gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH)is the second major contributor to azathioprine breakdown, polymorphisms inXDHhave rarely been studied in IBD patients. We aim to access association betweenXDHvariants and thiopurine-induced leukopenia by gene–gene interaction in a Crohn’s disease (CD) population.StudyA total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between fourXDHvariants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia,NUDT15(p.Arg139Cys),SUCLA2(p.Ser199Thr), andTPMT *3Cwere selected for epistasis analysis with theXDHvariants.ResultsThere was no significant association for two variants ofXDHand thiopurine-induced leukopenia. In the epistasis analysis, onlyXDH(p.Asn1109Thr) *SUCLA2(p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16;p = 0.03]. After genotype stratification, a positive association on the background ofSUCLA2wild-type (199Ser) between theXDH(p.Asn1109Thr) and early leukopenia (OR = 4.39;p = 0.01) was detected.ConclusionGenes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination ofXDH(p.Asn1109Thr) andSUCLA2(199Ser) on thiopurine-induced leukopenia. [ABSTRACT FROM PUBLISHER]

Objective. Limited data are available on the incidence and risk factors of colorectal cancer (CRC) in Asian patients with inflammatory bowel disease (IBD). Material and methods. Information on 5212 Korean patients with IBD (2414 with Crohn's disease [CD] and 2798 with ulcerative colitis [UC]) was retrieved from the IBD registry of Asan Medical Center. Data on CRC incidence for the entire Korean population were derived from the Korean Statistical Information Service. Results. During 39,951 person-years of follow-up (17,679 for CD and 22,272 for UC), 30 patients (12 with CD and 18 with UC) developed CRC. The standardized incidence ratio (SIR) of CRC was 6.0 (95% confidence interval [CI], 3.10-10.48) for CD and 1.68 (95% CI, 1.00-2.66) for UC; it was 9.69 (95% CI, 5.01-16.93) for CD with colonic involvement and 4.31 (95% CI, 2.46-7.00) for extensive UC. The SIR was also increased in patients diagnosed with IBD at younger than 30 years old. CRC location was the low rectum in 11 of 12 CD patients (91.7%). The cumulative probability of rectal cancer was higher in CD patients with a perianal fistula than in those without a perianal fistula ( p = 0.02). Conclusions. A high prevalence of perianal fistulas in Korean CD patients may be the cause of the predominance of low rectal cancer in this population and the higher SIR of CRC in Koreans than in Westerners. In contrast, the SIR of CRC in Korean UC patients may be similar to that in Western UC patients. [ABSTRACT FROM AUTHOR]

Objective. Recent studies have suggested that the clinical characteristics and genetic background of Crohn's disease (CD) patients differ between Asian and Caucasian individuals. However, the clinical features and course of CD in Asian patients remain unclear. Therefore, we investigated the clinical features and long-term prognosis of CD in a Korean population. Material and methods. We retrospectively analyzed 278 Korean patients with CD first diagnosed at the Asan Medical Center between March 1991 and February 2007. Results. The male-to-female ratio was 2.2:1 and the median age at diagnosis was 23 years. The median duration of follow-up was 71 months (range, 1–210 months). At diagnosis, 187 patients (67.3%) had disease in both small bowel and colon, 68 (24.4%) had isolated small bowel disease, and 23 (8.3%) had isolated colonic disease. The number of patients with stricturing or penetrating behavior as defined by the Montreal classification increased from 87 (31.3%) at diagnosis to 141 (50.7%) at final evaluation. One hundred and thirty patients (46.8%) experienced perianal fistulas before and/or after diagnosis of CD. A total of 71 patients (25.5%) underwent intestinal resection and the cumulative probability of intestinal resection after 1, 5, and 10 years was 15.5%, 25.0%, and 32.8%, respectively. Conclusions. Korean CD patients differed from Western patients in gender distribution, disease location, and perianal fistula occurrence. Korean CD patients may also have better clinical courses than Western patients, as indicated by the lower intestinal resection rate. [ABSTRACT FROM AUTHOR]