Korean Ulcerative Colitis Patients Research Articles

P630 Identification of specific cell subsets related to treatment response after anti-tumor necrosis factor use in Korean ulcerative colitis patients using single cell RNA sequencing: a preliminary study

Abstract Background The breakdown of the epithelial barrier and mucosal homeostasis plays an important role in the development of ulcerative colitis (UC). Recently, single-cell RNA sequencing (scRNA-seq) has been performed to better understand the gene expression patterns and the characteristics of cells in intestine of UC patients. However, there is a lack of studies focus on Asian UC patients. The aim of this preliminary study was to identify the relevant cellular subsets related to treatment response after anti-tumor necrosis factor (anti-TNF) use in Korean UC patients using scRNA-seq. Methods This prospective study was conducted two University hospitals in Korea. We performed scRNA-seq on sigmoid colon tissue samples collected from one healthy control and nine biologic naïve UC patients scheduled to use anti-TNF due to lack of response to conventional therapy. All mucosal biopsies from active moderate to severe UC were collected at baseline (n=9) and at 52 weeks follow-up after anti-TNF use (n=2), at which time treatment response was assessed. Treatment responder was defined as those with sustained clinical remission (a partial Mayo score of ≤2 with no subscore >1 and a rectal bleeding subscore of 0) at 52 weeks. Results After processing the scRNA-seq data, 13 clusters were discovered and cell clusters were annotated using colon marker gene. Among nine patients, two patients who underwent response evaluation at 52 weeks after anti-TNF use were treatment responder. The normalized proportion of cluster 1 (stem cell-like cluster) in 52 weeks follow-up tissue samples after anti-TNF use was shown to be decreased significantly (p-value=0.03) from that found in the disease tissue samples. A decrease in the proportion of cell cluster 1 from disease tissue samples’ initial average percentage (30.6%) down to an average of 4.8% in the follow-up tissue samples is quite substantial (p-value=0.03). This decrease signifies a notable change in the composition of this specific cell cluster post-anti-TNF treatment. Moreover, reaching a level close to that of the healthy tissue sample (2.7%) suggests a potential restoration of this cell cluster's proportion towards a healthier state (Figure 1). Conclusion In Korean UC patients, this information should be crucial in understanding the impact of anti-TNF treatment on the cellular composition or behavior of this stem cell-like cluster, suggesting a potential effect of anti-TNF treatment on this particular cell population.

P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective study

Abstract Background Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC. Methods This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP. Results A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p<0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01). Conclusion Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.

P833 Cervical cancer risk in newly diagnosed ulcerative colitis: a nationwide population-based study

Abstract Background The association between ulcerative colitis (UC) and increased risk of cervical cancer in women remains controversial. We investigated cervical cancer risk in South Korean UC patients using the Korean National Health Insurance (NHI) claims data. Methods UC definitions included both ICD-10 codes and UC-specific prescriptions. We analyzed incident cases diagnosed between 2006 and 2015. Age-matched women without UC (control group) were randomly selected from the general population (1:3 ratio). Hazard ratios (HRs), adjusted for different covariates, were calculated using multivariate Cox proportional hazard regression. In total, 12,632 and 36,797 women with and without UC, respectively, were enrolled. Results Cervical cancer developed in 0.21% (68 person-years) and 0.14% (172 person-years) of UC patients and controls, respectively. The HR (95% CI) of cervical cancer in the UC group, with reference to the control group, was 1.56 (0.97-2.50). HR, stratified by age, was significantly high in elderly UC patients (≥60 years) at 3.65 (1.54–8.66). In UC patients, old age (≥40 years) and low socioeconomic status were associated with increased cervical cancer risk. Conclusion Elderly UC patients had a higher incidence of cervical cancer than age-matched controls in Korea, suggesting that elderly patients with newly diagnosed UC should be screened for cervical cancer.

Risks of colorectal cancer and biliary cancer according to accompanied primary sclerosing cholangitis in Korean patients with ulcerative colitis: a nationwide population-based study.

We conducted a nationwide population-based study to investigate incidence rates of colorectal and biliary cancers according to accompanying primary sclerosing cholangitis in Korean ulcerative colitis patients. We used the Health Insurance Review and Assessment claim database from January 2007 to April 2020. Standardized incidence ratios of colorectal and biliary cancers in ulcerative colitis patients were calculated. Among 35,189 newly diagnosed ulcerative colitis patients, 1,224 patients were diagnosed with primary sclerosing cholangitis. During the study period, 122 and 52 patients were diagnosed with colorectal and biliary cancers, respectively. Incidences of colorectal cancer were not higher in ulcerative colitis patients than those in the general population (standardized incidence ratios, 0.83; 95% confidence interval, 0.69-0.99), regardless of accompanied primary sclerosing cholangitis (standardized incidence ratio, 0.73; 95% confidence interval, 0.24-1.71). While incidences of biliary cancer were not higher in ulcerative colitis patients than those in the general population (standardized incidence ratio, 1.14; 95% confidence interval, 0.80-1.58), these were much higher with accompanied primary sclerosing cholangitis (standardized incidence ratio, 10.07; 95% confidence interval, 5.75-16.36). Cumulative incidences of colorectal and biliary cancers increased in patients who were diagnosed with ulcerative colitis at an older age. In Korean ulcerative colitis patients, colorectal cancer incidences were not higher than those in the general population regardless of accompanied primary sclerosing cholangitis. However, biliary cancer incidences were much higher in ulcerative colitis patients with primary sclerosing cholangitis than in those without, or in the general population.

Oral beclomethasone dipropionate as an add-on therapy and response prediction in Korean patients with ulcerative colitis.

We aimed to investigate the oral beclomethasone dipropionate's (BDP) efficacy as an add-on therapy and to clarify the predictive factor for response to oral BDP in Korean ulcerative colitis (UC) patients. Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before BDP initiation were included. Partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a post-treatment pMS ≤ 1 point. Clinical response (CRES) was defined as an at least 2-point decrease in post-treatment pMS and an at least 30% decrease from baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Of all, 37 showed CREM, 19 showed CRES, and 44 were NRs. The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, p = 0.011) than NRs. In contrast to NRs, CREM and CRES patients showed significant improvement of post-treatment erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (ESR with p = 0.001, CRP with p = 0.004, respectively). Moreover, the initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with p < 0.001). In multivariate analyses, initial stool frequency subscore (SFS) of 0 and RBS of 0 were predictive factors for CREM (odds ratio [OR], 15.359; 95% confidence interval [CI], 1.085 to 217.499; p = 0.043 for SFS, and OR, 11.434; 95% CI, 1.682 to 77.710; p = 0.013 for RBS). Oral BDP is an efficacious add-on therapy in Korean UC patients. Patients with initial SFS or RBS of 0 may be particularly good candidates for oral BDP.

P448 Oral beclomethasone dipropionate as an add-on therapy and response prediction in Korean patients with ulcerative colitis

Abstract Background We aimed to investigate the efficacy of oral beclomethasone dipropionate (BDP) as an add-on therapy to concomitant drugs and to clarify the predictive factors for response to oral BDP in Korean patients with ulcerative colitis (UC). Methods Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before initiation were included. The partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a posttreatment pMS ≤1 point. Clinical response (CRES) was defined as an at least 2-points decrease in the posttreatment pMS and an at least 30% decrease from the baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Results Of total 100 patients, 37 showed CREM, 19 showed CRES, and 44 were NRs (Table 1). The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, P=0.011) than the NR group. In contrast to NR group, responders including CREM and CRES showed significant improvement of posttreatment ESR and CRP (ESR with P=0.001, CRP with P=0.004, respectively). Moreover, initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with P<0.001). In multivariate logistic regression analysis, initially mild disease activity was the only predictive factor for CREM (odds ratio, 3.580; 95% confidence interval, 1.342–9.548) (Table 2). Conclusion Oral BDP is efficacious as an add-on therapy in Korean UC patients. In case of acute aggravation, patients with mild disease activity, especially low RBS, may be good candidates for oral BDP.

Real-World Incidence of Suboptimal Response to Anti-Tumor Necrosis Factor Therapy for Ulcerative Colitis: A Nationwide Population-Based Study.

Background/AimsAlthough anti-tumor necrosis factor (TNF) agents have been widely used to treat ulcerative colitis (UC), the real-world incidence of suboptimal response to anti-TNF agents has not been thoroughly investigated, especially among Asians.MethodsUsing the Korean National Health Insurance database, we collected data on UC patients who initiated anti-TNF agents between July 1, 2014, and June 30, 2017. We assessed suboptimal responses, including anti-TNF discontinuation or dose escalation, switching to other biologics, augmentation with a non-biologic therapy, and the requirement for colectomy.ResultsA total of 1,268 patients were included as new anti-TNF users (infliximab 713, adalimumab 433, golimumab 122). The proportion of patients who experienced at least one suboptimal response within 1 year among all patients was 63.5%, including 59.1%, 69.5%, and 68.0% of patients treated with infliximab, adalimumab, and golimumab, respectively. The cumulative incidences of at least one suboptimal response over time were 41.5%, 63.7%, 80.5%, and 87.1% at 6, 12, 24, and 36 months, respectively. Cox proportional hazards modeling revealed that adalimumab was associated with a higher risk of at least one suboptimal response (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.13 to 1.48), dose escalation (HR, 4.35; 95% CI, 2.97 to 6.38) and discontinuation (HR, 1.25; 95% CI, 1.03 to 1.52) than infliximab. Golimumab was associated with a higher risk of switching to other biologics than infliximab (HR, 1.78; 95% CI, 1.21 to 2.60).ConclusionsMore than half of Korean UC patients had suboptimal responses to anti-TNF agents within 1 year. UC patients treated with infliximab might be less prone to suboptimal responses than those treated with adalimumab or golimumab.

P796 Annual prevalence and clinical outcomes of ulcerative colitis with primary sclerosing cholangitis in Korea over the last 10 years

Abstract Background The prevalence of ulcerative colitis (UC) in Korea has recently increased significantly, but there is few data for the prevalence and clinical outcomes of primary sclerosing cholangitis (PSC) associated UC. Thus, we assessed the prevalence of primary sclerosing cholangitis (PSC)and analysed clinical outcomes in Korean UC patients. Methods National Health Insurance System (NHIS) claim data from 2008 to 2017 were used in this population-based study. UC patients and PSC patients were identified by codes for ulcerative colitis (UC: K51) and (PSC: K830) in the NHIS registration system. Clinical events were defined as emergency department visit, hospitalisation, colectomy and liver transplantation. Results The overall number of UC with PSC & without PSC patients has increased steadily (Table 1). The prevalence of PSC in UC patients has increased since 2008 and was 0.33%in 2017.Clinical events were more frequent in UC with PSC, but the incidence of clinical events has decreased since 2008 in both groups (Figure 1).In 2017, the number of UC with PSC was 189 (male;118 vs. female;71) and the mean age of UC with PSC was 50.82 years(vs. UC without PSC;49.74). The incidence was low in teenagers and there was no difference in prevalence by age group. Conclusion This study confirmed that the prevalence of PSC is increasing in Korea. Additionally, UC with PSC patients have poor clinical outcomes. Therefore, the prevalence of PSC in UC patients suggests the need for greater attention and effort in clinical practice.

Long-term Outcomes of Adalimumab Therapy in Korean Patients with Ulcerative Colitis: A Hospital-Based Cohort Study.

Background/AimsStudies on long-term outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking.MethodsWe analyzed long-term outcomes of Korean UC patients treated with adalimumab at the Asan Medical Center, Seoul, Korea.ResultsBetween July 2013 and October 2018, adalimumab therapy was started in a total of 100 patients with UC (65 males [65.0%]; median age, 39.5 years [interquartile range, 23.3 to 49.8 years]; and median disease duration, 3.0 years [interquartile range, 1.0 to 7.0 years]). The median duration of adalimumab therapy was 13.5 months (interquartile range, 4.0 to 32.0 months). Eight of 100 patients (8.0%) received induction therapy only, four (4.0%) of whom ultimately underwent colectomy. Of 92 patients who received adalimumab maintenance therapy, 30 (30.0%) stopped adalimumab therapy due to loss of response, and one patient (1.0%) was lost to follow-up. Among the 92 patients who received adalimumab maintenance therapy, the cumulative proportions of patients remaining on adalimumab maintenance therapy were 70.0% at 1 year and 48.9% at 5 years. High partial Mayo score after 8 weeks of adalimumab therapy (hazard ratio [HR], 1.217; 95% confidence interval [CI], 1.040 to 1.425; p=0.014) and a history of exposure to two biologic agents before adalimumab therapy (HR, 4.722; CI, 1.033 to 21.586; p=0.045) were predictors of adalimumab discontinuation.ConclusionsLong-term outcomes of adalimumab therapy in Korean UC patients appear to be comparable to those in previously published Western studies. Furthermore, previous exposure to multiple biologic agents before adalimumab therapy and disease activity after 8 weeks of adalimumab therapy were predictors of adalimumab discontinuation.

Deep Resequencing of Ulcerative Colitis-Associated Genes Identifies Novel Variants in Candidate Genes in the Korean Population.

Genome-wide association studies and meta-analyses have revealed the genetic background of ulcerative colitis (UC) by identifying common variants. However, these variants do not fully explain the disease variance in UC. To identify novel variants, we performed deep resequencing of UC-associated genes in Korean UC patients and subsequently investigated the functional roles of identified susceptibility genes. We performed targeted deep resequencing of 108 genes in 24 Korean UC patients and then performed association analysis with data from 126 healthy controls. We validated these variants using 2-stage replication studies including 793 UC patients and 783 controls. We performed in silico and pathway analyses and functional analyses. The combined analysis including 2 replication studies identified 6 novel susceptibility loci and reconfirmed 10 previously reported loci. Among the novel single nucleotide variants (SNVs), rs10035653 in C5orf55 (P = 2.08 × 10-3; OR = 1.50), rs41417449 in BTNL2 (P = 1.27 × 10-2; OR = 1.32), rs3117099 in HCG23 (P = 9.98 × 10-6; OR = 1.40), rs7192 in HLA-DRA (P = 6.95 × 10-9; OR = 1.57), and rs3744246 in ORMDL3 (P = 2.21 × 10-2; OR = 1.21) were identified as causal variants, whereas rs713669 in IL17REL (P = 2.69 × 10-2; OR = 0.84) as a protective variant for UC. When correcting multiple testing, 3 novel SNVs (rs41417449 in BTNL2, rs3744246 in ORMDL3, and rs713669 in IL17REL) and 4 previously reported SNVs did not reach a statistical significance. Functional study suggested that SNVs of BTNL2 and C5orf55 exacerbated the inflammatory response both in vitro and in vivo. This study identified 3 novel susceptibility loci and validated 6 previously reported SNVs for UC through deep resequencing in Koreans and revealed the functional roles of BTNL2 and C5orf55.

P048 HISTORY OF CYTOMEGALOVIRUS COLITIS IS ASSOCIATED WITH POOR LONG-TERM OUTCOMES IN ADALIMUMAB THERAPY IN KOREAN PATIENTS WITH ULCERATIVE COLITIS: A HOSPITAL-BASED COHORT STUDY

Studies regarding long-term outcomes of adalimumab treatment in non-Caucasian patients with ulcerative colitis (UC) are still lacking. We analyzed long-term outcomes of Korean UC patients on adalimumab treatment in Asan Medical Center, Korea. Between July 2013 and June 2017, adalimumab treatment was commenced on in 72 patients; 49 males (68.1%), median age 40.5 years (Interquartile range [IQR], 24.25–50.00), and median disease duration 39.5 months (IQR, 22.00–85.00) at initiation of adalimumab. Twelve patients (16.7%) had a history of cytomegalovirus colitis within 3 months prior to starting adalimumab. Median duration of adalimumab therapy was 10.50 months (IQR, 2.00–26.75). Seventeen out of 72 patients (23.6%) were primary non-responders, and 7 out of those (9.7%) finally received colectomy. Out of 55 patients who received scheduled adalimumab maintenance therapy, 9 (16.4%) and 3 (5.5%) stopped adalimumab treatment due to loss of response and patients’ preference for discontinuation/loss to follow-up, respectively. Adalimumab dose intensification was required in 22 (40.0%) and corticosteroid rescue therapy was needed in 15 (27.3%) out of 55 patients during adalimumab maintenance therapy. The cumulative proportion of patients without adalimumab discontinuation was 61.0% at 1 year and 56.5% at 3 years among 72 patients who received adalimumab treatment more than once, and 80.1% at 1 year and 74.1% at 3 years among 55 patients who received adalimumab maintenance therapy. History of cytomegalovirus colitis within 3 months prior to starting adalimumab treatment was turned to be a predictor of adalimumab discontinuation (hazard ratio, 3.976; 95% confidence interval, 1.149–13.755; p = 0.029). Long-term outcomes of adalimumab treatment in Korean UC patients appears to be comparable to Western studies. Furthermore, a recent history of cytomegalovirus colitis was a predictor for adalimumab discontinuation.

P048 HISTORY OF CYTOMEGALOVIRUS COLITIS IS ASSOCIATED WITH POOR LONG-TERM OUTCOMES IN ADALIMUMAB THERAPY IN KOREAN PATIENTS WITH ULCERATIVE COLITIS: A HOSPITAL-BASED COHORT STUDY

Studies regarding long-term outcomes of adalimumab treatment in non-Caucasian patients with ulcerative colitis (UC) are still lacking. We analyzed long-term outcomes of Korean UC patients on adalimumab treatment in Asan Medical Center, Korea. Between July 2013 and June 2017, adalimumab treatment was commenced on in 72 patients; 49 males (68.1%), median age 40.5 years (Interquartile range [IQR], 24.25-50.00), and median disease duration 39.5 months (IQR, 22.00-85.00) at initiation of adalimumab. Twelve patients (16.7%) had a history of cytomegalovirus colitis within 3 months prior to starting adalimumab. Median duration of adalimumab therapy was 10.50 months (IQR, 2.00-26.75). Seventeen out of 72 patients (23.6%) were primary non-responders, and 7 out of those (9.7%) finally received colectomy. Out of 55 patients who received scheduled adalimumab maintenance therapy, 9 (16.4%) and 3 (5.5%) stopped adalimumab treatment due to loss of response and patients’ preference for discontinuation/loss to follow-up, respectively. Adalimumab dose intensification was required in 22 (40.0%) and corticosteroid rescue therapy was needed in 15 (27.3%) out of 55 patients during adalimumab maintenance therapy. The cumulative proportion of patients without adalimumab discontinuation was 61.0% at 1 year and 56.5% at 3 years among 72 patients who received adalimumab treatment more than once, and 80.1% at 1 year and 74.1% at 3 years among 55 patients who received adalimumab maintenance therapy. History of cytomegalovirus colitis within 3 months prior to starting adalimumab treatment was turned to be a predictor of adalimumab discontinuation (hazard ratio, 3.976; 95% confidence interval, 1.149-13.755; p = 0.029). Long-term outcomes of adalimumab treatment in Korean UC patients appears to be comparable to Western studies. Furthermore, a recent history of cytomegalovirus colitis was a predictor for adalimumab discontinuation.

Long-term outcomes of infliximab treatment and predictors of response in 195 patients with ulcerative colitis: a hospital-based cohort study from Korea

Background: Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking.Study: We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX.Results: Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients’ preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04–2.37; p = .032).Conclusions: The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies.

Postoperative changes of manometry after restorative proctocolectomy in Korean ulcerative colitis patients.

AIMTo investigate the changes of postoperative anal sphincter function and bowel frequency in Korean patients with ulcerative colitis (UC).METHODSA total of 127 patients with UC who underwent restorative proctocolectomy (RPC) during 20 years were retrospectively analyzed. The parameters of anal manometry and bowel frequency were compared according to the 6-mo intervals until 24 mo postoperatively. Manometry was used to measure the maximal squeezing pressure (MSP) and maximal resting pressure (MRP).RESULTSMSP decreased after surgery until 6 mo (157 to 142 mmHg); thereafter, it improved and was recovered to and maintained at the preoperative value at 12 mo postoperatively (142-170 mmHg, P < 0.001). Although the decreased MRP (65 to 56 mmHg) improved after 18 mo (62 mmHg), it did not completely recover to the preoperative value. The decreased rectal capacity after surgery (90 to 82 mL) gradually increased up to 150 mL at 24 mo. Although bowel frequency showed significant gradual decreases at each interval, it was stabilized after 12 mo postoperatively (6.5 times/d).CONCLUSIONPostoperative changes of manometry and bowel frequency after restorative proctocolectomy in Korean patients with UC were not different from those in Western patients with UC.

Increased risk of asymptomatic gallstones in patients with ulcerative colitis.

Background/AimsThe relationship between Crohn's disease and gallstones is established. However, the prevalence and risk factors for gallstones in patients with ulcerative colitis (UC) are not yet well understood. The aim of this study was to evaluate the prevalence and risk factors of gallstones in patients with UC.MethodsThis study was a retrospective single center study. A total of 87 patients with UC and 261 healthy controls were enrolled. Age, sex, and body mass index were matched. To investigate risk factors, the extent of UC, duration of disease, number of hospital admissions, and number of steroid treatments in patients with UC were evaluated.ResultsThe prevalence of gallstones in patients with UC was 13.8%, whereas that in healthy controls was only 3.1% (P<0.001). For patients with UC, patients ≥50 years of age had a 3.6-times higher risk of gallstones compared to that in those <50 years of age, and the difference was statistically significant (odds ratio, 3.60; confidence interval, 1.03-12.61) in univariate analysis. There were no statistically significant disease-related risk factors for gallstones in UC patients.ConclusionsThis is the first study of gallstone prevalence in Korean UC patients. In this study, patients with UC had a higher prevalence of gallstones compared to that in well-matched healthy controls. Age seemed to be a possible risk factor, and more studies are needed. Further prospective, large-scale studies will be required to confirm the risk factors for gallstones in UC patients.

Long-term prognosis of ulcerative colitis and its temporal change between 1977 and 2013: a hospital-based cohort study from Korea.

No previous large-scale studies have evaluated the prognosis of ulcerative colitis (UC) over a period of three decades in a non-Caucasian population. The aims of this study were to update the current information on the natural course of UC in a sizable cohort of Korean patients and to evaluate changes in the treatment paradigms and prognosis of UC over time. We retrospectively analyzed 2802 Korean UC patients who visited Asan Medical Center. We divided the study subjects into three groups based on the year of diagnosis (cohort 1: 1977–1999; cohort 2: 2000–2006; and cohort 3: 2007–2013). Five-year cumulative probabilities of prescription of thiopurines (azathioprine or 6-mercaptopurine) and anti-tumor necrosis factor (anti-TNF) agents were 4.1% and 0.0%, respectively, in cohort 1 and 27.9% and 12.7%, respectively, in cohort 3 (P < 0.001). A total of 209 patients (7.5%) underwent colectomy, producing cumulative probabilities of colectomy at 10, 20 and 30 years after diagnosis of 7.8%, 14.2% and 21.3%, respectively. The cumulative probability of colectomy was especially low in patients first diagnosed at our center: 3.1% at 10 years and 4.5% at 20 years. Moreover, the cumulative probability of colectomy decreased significantly over the last 30 years (P = 0.039). Thiopurines and anti-TNF agents are used increasingly more frequently and earlier, while the colectomy rate has decreased over the last 30 years in Korean patients with UC. Korean UC patients may have a better clinical course than Western cases, as indicated by a lower colectomy rate.

Clinical course of infliximab treatment in korean pediatric ulcerative colitis patients: a single center experience.

PurposeInfliximab (IFX) is considered safe and effective for the treatment of ulcerative colitis (UC) in both adults and children. The aim of this study was to evaluate the short- and long-term clinical course of IFX in Korean children with UC.MethodsPediatric patients with UC who had received IFX infusions between November 2007 and May 2013 at Samsung Medical Center were retrospectively investigated. The clinical efficacy of IFX treatment was evaluated at 8 weeks (short term) and 54 weeks (long term) after the initiation of IFX treatment using the Pediatric Ulcerative Colitis Activity Index (PUCAI). The degree of response to IFX treatment was defined as complete response (PUCAI score=0), partial response (decrement of PUCAI score≥20 points), and non-response (decrement of PUCAI score <20 points). Adverse events associated with IFX treatment were also investigated.ResultsEleven pediatric patients with moderate to severe UC had received IFX. The remission rate after IFX treatment was 46% (5/11) and 82% (9/11) at 8 weeks and 54 weeks after IFX treatment, respectively. All patients who were steroid-dependent before treatment with IFX achieved remission at 54 weeks and were able to stop treatment with corticosteroids, while all steroid-refractory patients failed to achieve remission at 54 weeks after treatment with IFX.ConclusionResponse to IFX treatment after 8 weeks may predict a favorable long-term response to IFX treatment in Korean pediatric UC patients.

Severe Disease Activity and Cytomegalovirus Colitis Are Predictive of a Nonresponse to Infliximab in Patients with Ulcerative Colitis

The role of infliximab in the treatment of patients with ulcerative colitis (UC) in Asia is still unclear. The aim of this study was to evaluate the clinical outcomes of infliximab therapy in Korean UC patients, including efficacy and predictors of response. Patients who received infliximab induction therapy for moderate to severe UC at Asan Medical Center were retrospectively analyzed. The demographic characteristics of these patients and their clinical outcomes following infliximab therapy were evaluated. Of the 89 UC patients receiving infliximab induction therapy, 53 (59.6%) were steroid-refractory and 36 (40.4%) were steroid-dependent. At the initiation of infliximab, the median Mayo score was 9 (range 7-12). After the induction therapy of infliximab, 59 patients (66.3%) demonstrated a clinical response at week 8, of which 29 (32.6%) were determined to be in clinical remission. A colectomy was performed within 1 year after infliximab initiation in 11 (36.7%) of 30 patients who displayed no clinical response to infliximab therapy, but in none of the 59 patients who showed a response to this drug (p<0.001). Multivariate regression analysis identified severe disease (Mayo score≥11) at the initiation of infliximab (p=0.007) and history of cytomegalovirus colitis within 3 months prior to infliximab treatment (p=0.001) as independent positive predictors of nonresponse to infliximab. The efficacy of infliximab in Korean UC patients seems to be similar to that of previously published Western reports. Severe disease and a history of cytomegalovirus colitis are predictors of a nonresponse to infliximab.

Long-term clinical outcomes and factors predictive of relapse after 5-aminosalicylate or sulfasalazine therapy in patients with mild-to-moderate ulcerative colitis.

Clinical outcomes and factors predictive of favorable response after 5-aminosalicylates or sulfasalazine (5-ASA/sulfasalazine) treatment alone have not been well established in the treatment of mild to moderate ulcerative colitis (UC). We evaluated the clinical course of Korean UC patients treated with 5-ASA/sulfasalazine as a maintenance therapy in terms of relapse and predictive factors of clinical relapse. A total 256 UC patients, treated with 5-ASA/sulfasalazine at the Severance Hospital between January 2000 and December 2008, were analyzed retrospectively. We sought to investigate relapse rates and to determine independent predictors for relapse. Of the 256 patients, 127 patients (49.6%) had a disease relapse. The cumulative relapse rate was 21.5% after 1 year, 36.5% after 2 years, 46.9% after 3 years and 59.8% after 5 years. On multivariate analysis, left-sided or extensive colitis at diagnosis (hazard ratio=1.46; 95% CI=1.01-2.10; p=0.04) and initial hemoglobin level <10.5g/dL (hazard ratio= 0.43; 95% CI=0.22-0.81; p=0.01) were found to be independent factors for clinical relapse. Our study showed that both disease extent at diagnosis and anemia were major predictive factors for clinical relapse after 5-ASA/sulfasalazine therapy for Korean patients with mild to moderate UC.

Clinical characteristics of ulcerative colitis associated with primary sclerosing cholangitis in Korea

Primary sclerosing cholangitis (PSC) is well known as one of the extraintestinal manifestations of ulcerative colitis (UC). However, the prevalence of PSC in UC patients together with the clinical characteristics and outcomes of UC associated with PSC (UC-PSC) are not clear in Asians. We retrospectively reviewed the medical records of UC patients who were registered and followed up at the Asan Medical Center. The prevalence of PSC in UC and the clinical features of UC-PSC compared with matched UC without PSC were investigated. A total of 1849 patients diagnosed with UC between July 1977 and September 2009 were reviewed. Among these, 21 UC-PSC patients (1.1%) were identified. The cumulative probability of PSC after diagnosis of UC was 0.71% after 1-5 years, 1.42% after 10 years, 2.59% after 15 years, and 3.35% after 20-25 years. Compared with 63 matched UC alone patients, UC-PSC showed pancolitis (95.2%), rectal sparing (38.1%), and backwash ileitis (42.9%) more frequently (P < 0.001). During follow-up, three of 21 UC-PSC patients (14.3%) were diagnosed with colorectal neoplasia and three patients (14.3%) died of PSC-associated complications. UC-PSC patients were associated with increased probability of colorectal neoplasia development (P = 0.036) and a trend toward increased mortality compared with the UC alone group. The prevalence of PSC in Korean UC patients appears to be lower than that of Western patients. Similar to Caucasians, UC-PSC shows unique colonoscopic features and is associated with more frequent colorectal neoplasia development and poor prognosis in Korea.