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Background/Aims: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. Methods: This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. Results: During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. Conclusions: PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Long-term outcomes of cytomegalovirus reactivation in patients with moderate to severe ulcerative colitis" that was published in the previous issue, is presented.

Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet’s disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. [ABSTRACT FROM AUTHOR]

Background/Aims: Owing to the low prevalence of small-bowel adenocarcinoma (SBA), data on the impact of Crohn’s disease (CD) on the survival of patients with SBA are lacking. Therefore, we investigated this issue in this study. Methods: In this bicenter cohort study, patients with histologically confirmed SBA were retrospectively enrolled and classified into two groups: sporadic SBA and CD-associated SBA. Patients with duodenal SBA were excluded. Overall survival, disease-free survival, and factors associated with survival were analyzed. Results: Of 128 patients with SBA, 115 had sporadic SBA and 13 had CD-associated SBA. Ileal involvement and poorly differentiated tumors were more common in the CD-associated SBA group than in the sporadic SBA group (ileal involvement, 53.8% vs 22.6%; poor differentiation, 46.2% vs 14.8%; both p<0.05). In survival analysis, overall survival showed no statistical difference between the sporadic SBA and CD-associated SBA groups (p=0.370). However, when stratified by stage, the adjusted overall survival of the CD-associated SBA group was lower in patients with an advanced disease stage (p=0.029). Disease-free survival showed the same tendency, albeit without clinical significance (p=0.097). CD (hazard ratio [HR], 2.308; p=0.047), older age (≥65 yr) at SBA diagnosis (HR, 2.766; p=0.001), and stage III/IV disease (HR, 3.151; p<0.001) were factors associated with mortality. Conclusions: The overall survival of patients with CD-associated SBA did not differ from that of patients with sporadic SBA. However, as CD is an independent risk factor for mortality, vigilant surveillance in high-risk patients may be crucial. [ABSTRACT FROM AUTHOR]

The clinical course and prognosis of patients with elderly-onset Crohn’s disease (CD) remain unclear. This study aimed to analyze the clinical characteristics and outcomes of elderly-onset CD patients from the prospective CONNECT study cohort, a nationwide, multicenter cohort study of patients with CD in Korea. Among a total of 1,175 patients in the prospective CONNECT study cohort, 94 patients (Montreal age A3) were included and divided into two groups according to their age at diagnosis: the elderly-onset group (diagnosed with CD after 60 years of age, n=26, 67.54±6.7 years) and late adult-onset group (diagnosed as CD at age 41 to 59 years, n=68, 48.06±5.1 years). The elderly-onset group was characterized by a lower Crohn’s disease activity index at diagnosis (124.89±101.9 vs 189.55±128.6, p=0.023) and higher rates of previous anti-tuberculosis treatment (34.6% vs 4.4%, p<0.001) than the late adult-onset group. Compared with the late adult-onset group, the elderly-onset group showed a significantly less use of thiopurines (p=0.003), as well as anti-tumor necrosis factor-alpha agents (p=0.047). Additionally, the elderly-onset group was less likely to require bowel resection than the late adult-onset group (p=0.067), suggesting that elderly-onset CD patients in Korea appear to have more favorable clinical outcomes than late adult-onset CD patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Improving quality of life has been gaining importance in ulcerative colitis (UC) management. The aim of this study was to investigate changes in health-related quality of life (HRQL) and related factors in patients with moderate-to-severe UC. Methods: A multicenter, hospital-based, prospective study was performed using a Moderate-to-Severe Ulcerative Colitis Cohort in Korea (the MOSAIK). Changes in HRQL, evaluated using the 12-Item Short Form Health Survey (SF-12) and Inflammatory Bowel Disease Questionnaire (IBDQ), were analyzed at the time of diagnosis and 1 year later. Results: In a sample of 276 patients, the mean age was 38.4 years, and the majority of patients were male (59.8%). HRQL tended to increase in both the IBDQ and SF-12 1 year after diagnosis. A higher partial Mayo score was significantly related to poorer HRQL on the IBDQ and SF-12 in a linear mixed model (p<0.01). Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate also showed a negative correlation on HRQL (p<0.05). Patients whose IBDQ score improved by 16 or more (71.2%) in 1 year were younger, tended to be nonsmokers, and had a lower partial Mayo score and CRP than those whose IBDQ score did not. There was no significant association between HRQL and disease extent, treatments at diagnosis, or the highest treatment step during the 1-year period. Conclusions: Optimally controlled disease status improves HRQL in patients with moderate-to-severe UC. The partial Mayo score and inflammatory markers may be potential indicators reflecting the influence of UC on patient`s daily lives. [ABSTRACT FROM AUTHOR]

Background/Aims: Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the longterm outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment. Methods: This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated. Results: The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state. Conclusions: The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation. [ABSTRACT FROM AUTHOR]

Background/Aims: The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. Methods: A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. Results: A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). Conclusions: Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma. [ABSTRACT FROM AUTHOR]

Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68). Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to evaluate the clinical characteristics and long-term prognosis of elderly-onset ulcerative colitis (EOUC) in Korean patients over a 30-year period using a well-established population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Methods: Clinical characteristics and prognosis were compared between two groups: EOUC, defined as UC diagnosed in individuals aged ≥60 years and non-EOUC (N-EOUC), defined as UC diagnosed in individuals aged 18 to 59 years. Results: We identified 99 patients with EOUC (10.3%) and 866 patients with N-EOUC (89.7%) between 1986 and 2015. During the median follow-up of 104.5 months, the overall exposure to medications was comparable between patients with EOUC and N-EOUC (p=0.091 for corticosteroids, p=0.794 for thiopurines, and p=0.095 for anti-tumor necrosis factor agents). The cumulative risks of disease outcomes were also comparable between patients with EOUC and N-EOUC (22.4% vs 30.4% for proximal disease extension [p=0.351], 11.9% vs 18.1% for hospitalization [p=0.240], and 2.3% vs 1.8% for colectomy [p=0.977]) at 10 years after diagnosis. Multivariate Cox regression analysis revealed that corticosteroid use at diagnosis was an independent predictor of proximal disease extension (hazard ratio [HR], 6.216; 95% confidence interval [CI], 1.314 to 28.826) and hospitalization (HR, 11.241; 95% CI, 3.027 to 41.742) in patients with EOUC. Conclusions: In this population-based study from Korea, the pattern of medication use seemed comparable between the EOUC and N-EOUC groups. Moreover, patients with EOUC and those with N-EOUC have a similar disease course in terms of proximal disease extension, hospitalization, and colectomy. [ABSTRACT FROM AUTHOR]

Background/Aims: The risk for colonoscopic postpolypectomy bleeding (PPB) in patients with chronic liver disease (CLD) remains unclear. We determined the incidence and risk factors for colonoscopic PPB in patients with CLD, especially those with liver cirrhosis. Methods: We retrospectively reviewed the medical records of patients with CLD who underwent colonoscopic polypectomy at Seoul National University Hospital between 2011 and 2014. The study endpoints were immediate and delayed PPB. Results: A total of 1,267 consecutive patients with CLD were included in the study. Immediate PPB occurred significantly more often in the Child- Pugh (CP) B or C cirrhosis group (17.5%) than in the CP-A (6.3%) and chronic hepatitis (4.6%) groups (p<0.001). Moreover, the incidence of delayed PPB in the CP-B or C cirrhosis group (4.4%) was significantly higher than that in the CP-A (0.7%) and chronic hepatitis (0.2%) groups (p<0.001). The independent risk factors for immediate PPB were CP-B or C cirrhosis (p=0.011), a platelet count <50,000/μL (p<0.001), 3 or more polyps (p=0.017), endoscopic mucosal resection or submucosal dissection (p<0.001), and polypectomy performed by trainees (p<0.001). The independent risk factors for delayed PPB were CP-B or C cirrhosis (p=0.009), and polyps >10 mm in size (p=0.010). Conclusions: Patients with CP-B or C cirrhosis had an increased risk for bleeding following colonoscopic polypectomy. [ABSTRACT FROM AUTHOR]

Background/Aims: Ghrelin agonists are emerging prokinetic agents for treating gastroparesis. Although recent clinical trials have demonstrated their efficacy in patients with diabetic gastroparesis (DG), the impact of such agents on symptoms and gastric dysmotility remains unclear. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ghrelin agonists in patients with DG. Methods: A search of common electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials) was preformed, using keyword combinations that referenced ghrelin and DG and retrieving all eligible randomized controlled trials (RCTs) of ghrelin agonists versus placebo in patients with DG. The primary outcome measure was the change in patient-reported overall gastroparesis symptom scores. Secondary outcomes included the change in gastric emptying time, specific symptoms related to gastroparesis, and adverse events. A random-effects model was applied to all study outcomes. Heterogeneity among studies was determined by the chi-square test and I2 statistics. Results: We selected six RCTs of patients with DG (n=557) for meta-analysis. Ghrelin agonist administration (vs placebo) significantly improved overall gastroparesis symptoms (standardized mean difference, -0.34; 95% confidence interval, -0.56 to -0.13) and significantly improved symptoms related to gastroparesis, including nausea, vomiting, early satiety, and abdominal pain. Adverse events recorded for ghrelin agonists and placebo did not differ significantly. There was no significant heterogeneity among eligible studies. Conclusions: Compared with placebo, ghrelin agonists are effective and well-tolerated for the treatment of DG. [ABSTRACT FROM AUTHOR]

Background/Aims: Epigenetic change is one of the mechanisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigenetic changes of miR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. Methods: The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mucosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori -eradication and H. pylori -persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the methylation levels. Results: In the GC cell lines, the level of miR- 200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order. In the H. pylori -persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methylation decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. Conclusions: Epigenetic alterations of miR-200a/b may be implicated in H. pylori -induced gastric carcinogenesis. This field defect for cancerization is suggested to be improved by H. pylori eradication. [ABSTRACT FROM AUTHOR]

Background/Aims: Little is known about the national colonoscopy volume in Asian countries. This study aimed to assess the national colonoscopy volume in Korea over a 12- year period on the basis of a nationwide population-based database. Methods: We conducted a population-based study for colonoscopy claims (14,511,158 colonoscopies performed on 13,219,781 patients) on the basis of the Korean National Health Insurance Service database from 2002 to 2013. The 12-year national colonoscopy burden was analyzed according to patient age, patient sex, and healthcare facility type. Results: The overall volume of colonoscopy increased 8-fold over the 12-year period. The annual colonoscopic polypectomy rate significantly increased in all patient sex and age groups over the 12-years period (all p<0.001). The yearly colonoscopic polypectomy rate for men was significantly increased compared with that for women (2.3% vs 1.7%, p<0.001) and for the screening-age group compared with that for the young-age group (2.0% vs 1.6%, p<0.001). The yearly colonoscopic polypectomy rate relative to the total colonoscopy volume significantly increased in primary, secondary, and tertiary facilities by 2.4%, 1.9%, and 1.4% during the 12-year period (all p<0.001). In addition, the annual colonoscopy volume covered by high-volume facilities significantly increased by 1.8% in primary healthcare facilities over the 12-year period (p<0.001). Conclusions: Healthcare resources should be prioritized to allow adequate colonoscopic capacity, especially for men, individuals in the screeningage group, and at primary healthcare facilities. Cost-effective strategies to improve the quality of colonoscopy may focus on primary healthcare facilities and high-volume facilities in Korea. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to investigate the differences in direct healthcare costs between patients with and without inflammatory bowel disease (IBD) and changes in direct healthcare costs before and after IBD diagnosis. Methods: This population-based study identified 34,167 patients with IBD (11,014 patients with Crohn's disease and 23,153 patients with ulcerative colitis) and 102,501 age-and sexmatched subjects without IBD (the control group) from the National Health Insurance database using the International Classification of Disease, 10th revision codes and the rare intractable disease registration program codes. The mean healthcare costs per patient were analyzed for 3 years before and after IBD diagnosis, with follow-up data available until 2015. Results: Total direct healthcare costs increased and peaked at $2,396 during the first year after IBD diagnosis, but subsequently dropped sharply to $1,478 during the second year after diagnosis. Total healthcare costs were higher for the IBD patients than for the control group, even in the third year before the diagnosis ($497 vs $402, p<0.001). The costs for biologics for the treatment of IBD increased steeply over time, rising from $720.8 in the first year after diagnosis to $1,249.6 in the third year after diagnosis (p<0.001). Conclusions: IBD patients incurred the highest direct healthcare costs during the first year after diagnosis. IBD patients had higher costs than the control group even before diagnosis. The cost of biologics increased steeply over time, and it can be assumed that biologics could be the main driver of costs during the early period after IBD diagnosis. [ABSTRACT FROM AUTHOR]

Background/Aims: The risk of herpes zoster (HZ) among patients with inflammatory bowel disease (IBD) remains un-clear in terms of age and metabolic comorbidities, including diabetes mellitus, hypertension, or dyslipidemia. We con-ducted a nationwide population based study to investigate the risk of HZ in patients with IBD. Methods: From 2010 to 2013, a retrospective study was performed using claims data in Korea. We compared the incidence of HZ between 30,100 IBD patients (10,517 Crohn's disease [CD] and 19,583 ul-cerative colitis [UC] patients) and 150,500 non-IBD controls matched by age and sex. Results: During a mean follow-up of 5.0 years, incidence rates of HZ (per 1,000 person-years) were 13.60, 14.99, and 9.19 in the CD, UC, and control groups, respectively. The risk of HZ was significantly higher in patients with CD (adjusted hazard ratio [HR], 2.13; p<0.001) and UC (adjusted HR, 1.40; p<0.001) than in the controls. The impact of CD on developing HZ was significantly more prominent in younger patients (adjusted HR, 2.61 for age <15, whereas 1.39 for age ≥60; interaction p=0.001) and in patients without metabolic comorbidities (adjusted HR, 2.24, whereas 1.59 in those with metabolic comorbidities; interac-tion p=0.015). Moreover, the impact of UC on developing HZ significantly increased in younger patients (adjusted HR, 2.51 in age <15, whereas 1.22 in age ≥60; interaction p=0.014) and patients without metabolic comorbidities (adjusted HR, 1.49 whereas 1.16 in those with metabolic comorbidities; interaction p<0.001). Conclusions: IBD was associated with an increased risk of HZ, especially in younger patients without metabolic comorbidities. [ABSTRACT FROM AUTHOR]

Background/Aims: The disease course and factors associated with poor prognosis in Korean patients with Crohn's disease (CD) have not been fully determined. The aim of this study was to explore potential associations between the clinical characteristics and long-term outcomes of CD and perianal fistulas in a Korean population. Methods: The retrospective Crohn's Disease Clinical Network and Cohort (CONNECT) study enrolled patients diagnosed with CD between July 1982 and December 2008 from 32 hospitals. Those followed for <12 months were excluded. Clinical outcomes were CD-related surgery and complications, including nonperianal fistulas, strictures, and intra-abdominal abscesses. Results: The mean follow-up period was 8.77 years (range, 1.0 to 25.8 years). A total of 1,193 CD patients were enrolled, of whom 465 (39.0%) experienced perianal fistulas. Perianal fistulizing CD was significantly associated with younger age, male gender, CD diagnosed at primary care clinics, and ileocolonic involvement. Both nonperianal fistulas (p=0.034) and intra-abdominal abscesses (p=0.020) were significantly more common in CD patients with perianal fistulas than in those without perianal fistulas. The rates of complicated strictures and CD-related surgery were similar between the groups. Independently associated factors of nonperianal fistulas were perianal fistulas (p=0.015), female gender (p=0.048), CD diagnosed at referral hospital (p=0.003), and upper gastrointestinal (UGI) involvement (p=0.001). Furthermore, perianal fistulas (p=0.048) and UGI involvement (p=0.012) were independently associated with the risk of intra-abdominal abscesses. Conclusions: Perianal fistulas predicted the development of nonperianal fistulas and intra-abdominal abscesses in Korean CD patients. Therefore, patients with perianal fistulizing CD should be carefully monitored for complicated fistulas or abscesses. [ABSTRACT FROM AUTHOR]

Background/Aims: The development of nonalcoholic fatty liver disease (NAFLD) is associated with multiple genetic and environmental factors. Methods: We performed a genomewide association study to identify the genetic factors related to NAFLD in a Korean population-based sample of 1,593 subjects with NAFLD and 2,816 controls. We replicated the data in another sample that included 744 NAFLD patients and 1,137 controls. We investigated single-nucleotide polymorphisms (SNPs) that were related to NAFLD. Results: After adjusting for age, sex and body mass index, rs738409, rs12483959 and rs2281135, located in the PNPLA3 gene, were validated in our population (p<8.56×10-8) in the same linkage disequilibrium block. Additionally, rs2143571, rs3761472, and rs2073080 in the SAMM50 gene showed significant associations with NAFLD (p<8.56×10-8). Furthermore, these six SNPs showed significant associations with the severity of fatty liver (all p<2.0×10-10 in the discovery set and p<2.0×10-6 in the validation set) and NAFLD, with elevated levels of alanine aminotransferase (all p<2.0×10-10 in the discovery set and p<2.0×10-6 in the validation set). Conclusions: We demonstrated that the PNPLA3 and SAMM50 genes are significantly associated with the presence and severity of NAFLD in a Korean population. These findings confirm the important roles of genetic factors in the pathogenesis of NAFLD. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastric mucosal atrophy and intestinal metaplasia due to Helicobacter pylori infection are the main precursor lesions of gastric cancer. The aim of this study was to evaluate the long-term effects of H. pylori eradication on the progression of precancerous lesions to metachronous cancer after endoscopic resection of early gastric cancer (EGC). Methods: Patients who underwent endoscopic resection of EGC were retrospectively reviewed. Changes in precancerous lesions and development of metachronous cancer were compared according to H. pylori eradication and final infection status. Results: In total, 565 patients were followed for over 5 years after endoscopic resection of EGC. The grade of atrophy on corpus was significantly lower in the H. pylorieradicated group than in the persistent group during followup (p=0.029). In patients <70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the H. pylori-eradicated group than in the persistent group (p=0.018). Age was an independent risk factor for metachronous cancer development. Conclusions: H. pylori eradication might prevent the development of metachronous cancer in patients <70 years of age by delaying the progression of precancerous lesions after endoscopic resection of EGC. [ABSTRACT FROM AUTHOR]

Background/Aims: We aimed to evaluate the clinical characteristics and prognosis of Crohn's disease (CD) in patients who showed proximal small bowel involvement using a nationwide Korean CD cohort. Methods: We reviewed the data from a cohort of patients diagnosed with CD. The clinical outcomes of patients were evaluated according to the presence of proximal small bowel involvement. Results: Among 1,329 patients with CD for whom complete disease location data were available, 222 patients (16.7%) showed involvement of the proximal small bowel. Compared to patients without proximal small bowel involvement, those with small bowel involvement were more likely to display stricturing behavior (19.8% vs 12.7%, p=0.020). The surgery-free survival of patients who showed proximal small bowel involvement was inferior to that of patients without proximal small bowel involvement (10-year surgery-free survival: 58.4% vs 67.7%, respectively, p<0.001). Additionally, upper gastrointestinal involvement was more common in patients with proximal small bowel involvement than in those without involvement (odds ratio, 1.643; 95% confidence interval, 1.008 to 2.677). Conclusions: Proximal small bowel involvement is a poor prognostic factor for the surgery-free survival of Korean patients with CD. Proximal small bowel involvement should be evaluated in patients with CD for predicting long-term clinical outcomes. (Gut Liver 2018;12:67-72) [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate whether Helicobacter pylori eradication can reverse epigenetic silencing of microRNAs (miRNAs) which are associated with H. pylori-induced gastric carcinogenesis. Methods: We examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell line, before/after demethylation. Among them, epigenetically controlled miRNAs were identified. Their expression and promoter methylation was examined in human tissues of H. pylori-positive gastric cancer (T), H. pyloripositive gastritis (H), and H. pylori-negative controls (C). We also compared changes of miRNA expression and promoter methylation in H. pylori -positive patients who were endoscopically treated for early gastric cancer, between baseline and 1 year later according to eradication status. Results: In gastric cancer cell line, miR-34b/c and miR-133a showed epigenetic silencing. In human tissues, miR-34b/c and miR133a showed serial increase of promoter methylation in order of C, H, and T (all, p<0.01), and the miR-133a expression showed serial decrease (C vs H, p=0.02; H vs T, p=0.01; C vs T, p<0.01) while miR-34b and miR-34c expressions did not. H. pylori eradication induced decrease of methylation (p<0.01) and increase of miR-133a expression (p=0.03), compared with noneradication group. Conclusions: This result suggests H. pylori eradication could reverse methylation-silencing of miR-133a which is involved in H. pylori-induced gastric carcinogenesis. (Gut Liver 2018;12:58-66) [ABSTRACT FROM AUTHOR]

Background/Aims: Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD. Methods: We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls. Results: Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; p<0.001). The proportions of patients with lower serum zinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn’s disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (<3.3 g/dL) (p=0.047) were risk factors for selenium deficiency. Conclusions: Many Korean patients with IBD have vitamin D, zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients. [ABSTRACT FROM AUTHOR]

Background/Aims: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. Methods: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). Results: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole- treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. Conclusions: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum. [ABSTRACT FROM AUTHOR]

Background/Aims: C-reactive protein (CRP) is an easily measured index of disease activity, but its ability to predict clinical course is controversial. We therefore designed a study to determine whether the CRP level at Crohn's disease (CD) diagnosis is a valuable indicator of the disease phenotype, activity, and clinical course. Methods: We retrospectively analyzed 705 CD patients from 32 institutions. The patients were classified into two groups according to CRP level. The patients' demographic and clinical characteristics and their use of immunosuppressive or biological agents were recorded. Disease location and behavior, hospitalization, and surgery were analyzed. Results: A high CRP was associated with younger age, steroid use, colonic or ileocolonic location, high CD activity index, and active inflammation at colonoscopy (p<0.001). As the disease progressed, patients with high CRP were more likely to exhibit strictures (p=0.027). There were significant differences in the use of 5-aminosalicylic acid, antibiotics, corticosteroids, azathioprine, and infliximab (p<0.001, p<0.001, p<0.001, p<0.001, and p=0.023, respectively). Hospitalization was also more frequent in patients with high CRP. Conclusions: The CRP level at diagnosis is useful for evaluating the phenotype, activity, and clinical course of CD. Closer follow-up strategies, with early aggressive treatment, could be considered for patients with high CRP. [ABSTRACT FROM AUTHOR]

Background/Aims: The optimal route for iron administration in anemic patients with inflammatory bowel disease (IBD) has not been determined. The aim of this study was to compare the efficacies of parenteral and oral iron therapy in IBD patients in Korea. Methods: A retrospective multicenter study was performed. Patients who had been administered parenteral iron were matched to the controls with oral iron at a 1:1 ratio according to age, sex, and type of IBD. Results: Patients that received parenteral iron exhibited increases in hemoglobin levels of ≥20% from the baseline at lower doses and in shorter durations (p=0.034 and p=0.046, respectively). In the multivariate analysis, parenteral iron therapy appeared to be more efficient than oral iron therapy, but this difference was not statistically significant (hazard ratio [HR], 1.552; 95% confidence interval [CI], 0.844 to 2.851; p=0.157). Patients with ulcerative colitis responded better to iron therapy than those with Crohn's disease (HR, 3.415; 95% CI, 1.808 to 6.450; p<0.001). Patients with an initial hemoglobin level of 10 g/dL or higher responded poorly to iron therapy (HR, 0.345; 95% CI, 0.177 to 0.671; p=0.002). Conclusions: Parenteral iron therapy appears to be more efficient than oral iron therapy. Physicians should focus on the iron deficiency of IBD patients and consider parenteral iron supplements in appropriate patient groups. [ABSTRACT FROM AUTHOR]

Background/Aims: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. Methods: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. Results: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 highgrade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). Conclusions: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms. [ABSTRACT FROM AUTHOR]

Background/Aims: The accurate preoperative prediction of the risk of malignancy of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study was to determine whether tumor size and endoscopic ultrasonography (EUS) features can preoperatively predict the risk of malignancy of medium-sized gastric GISTs. Methods: Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci, calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size or EUS features with the risk of malignancy were evaluated. Results: A total of 75 patients were enrolled. The mean tumor size was 3.43±0.92 cm. Regarding the risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had a moderate risk. When the tumors were divided into three groups in 1 cm intervals, the proportions of tumors with a moderate risk were not different between the groups. The preoperative EUS features also did not differ between the very low risk and the moderate risk groups. Conclusions: Tumor size and EUS features cannot be used to preoperatively predict the risk of malignancy of medium-sized gastric GISTs. A preoperative diagnostic modality for predicting risk of malignancy is necessary to prevent the overtreatment of GISTs with a low risk of malignancy. [ABSTRACT FROM AUTHOR]

Background/Aims: Helicobacter pylori infection induces cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) overexpression, and these factors may engage in cross-talk. The aim of the present study was to evaluate the effect of H. pylori on EGFR signaling pathways and to determine whether celecoxib has an inhibitory effect on this pathway. Methods: The AGS cell line was cocultured with H. pylori G27 and the isogenic cagE- mutant. The expression of COX-2, EGFR, heparin binding-epidermal growth factor (HB-EGF), and transforming growth factor-β (TGF-β) was measured by real time-polymerase chain reaction (RT-PCR). Next, Western blot analyses of COX-2, EGFR, total Akt, phosphorylated Akt (pAkt), and phosphorylated glycogen synthase kinase-3β (pGSK3β) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 μmol/L). Results: H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-β, as detected by RT-PCR. However, AGS cells treated with cagE- mutants, which have a defective type IV secretion system, did not exhibit EGFR upregulation. Celecoxib had inhibitory effects on the H. pylori-induced overexpression of COX-2 (p=0.015), EGFR (p=0.025), pAkt (p=0.025), and pGSK3β (p=0.029) by Western blot analysis. Conclusions: H. pylori with an intact type IV secretion system activated the COX-2 and EGFR-Akt pathways in the AGS cell line. As celecoxib exhibited inhibitory effects on the EGFR signaling pathway, the cross-talk of COX-2 and EGFR likely mediates H. pylori-induced gastric cancer. [ABSTRACT FROM AUTHOR]

Background/Aims Elevated serum gamma-glutamyltransferase (GGT) is associated with the incidence of digestive cancer. However, it is not clear whether the relationship between GGT and digestive cancer will be constant in accordance with diabetic status. Therefore, the aim of this study was to assess the association of GGT with digestive cancer stratified by diabetic status. Methods A total of 8,120,665 persons who received general medical check-up from January 2009 to December 2009 by the National Health Insurance Service were included. Subjects were classified according to quartile of GGT level (male: <21, 21-29, 30-47, and ≥48 IU/L; female: <13, 13-15, 16-22, and ≥23 IU/L) and incidence rates of esophageal, stomach, and colon cancer were analyzed for each group using Cox proportional hazards models. Stratified analyses were conducted by diabetic status (normal, prediabetes, and diabetes). Results During the 8-year follow-up, 129,853 cases of digestive cancer newly occurred. The highest GGT quartile group had an increased risk of digestive cancer compared to the lowest (esophagus: hazard ratio [HR], 2.408; 95% confidence interval [CI], 2.184 to 2.654; stomach: HR, 1.121; 95% CI, 1.093 to 1.149; colon: HR, 1.185; 95% CI, 1.158 to 1.211). When analyzed stratified by diabetic status, effect of GGT was predominant regarding the risk of esophageal cancer. However, the syngenetic effect with GGT and diabetes were identified in the incidence of stomach and colon cancer (stomach: HR, 1.283; 95% CI, 1.237 to 1.331; colon: HR, 1.342; 95% CI, 1.299 to 1.386, the highest GGT quartile in diabetes). In addition, groups with higher GGT in prediabetes showed higher risk of colon cancer compared to groups with lower GGT in diabetes. Conclusions Higher GGT was closely linked to the incidence of digestive cancer. The effect of GGT on the incidence of digestive cancer varies on type of cancer and diabetic status. [ABSTRACT FROM AUTHOR]

Background/Aims Periodontitis is caused by the interaction between microbiota in the root canal and host immune system. However, the effect of periodontitis on inflammatory bowel disease (IBD) is unclear. The aim of this study was to assess whether the incidence and risk of IBD increased in patients with periodontitis compared with general population. Methods We performed a nationwide, population-based study using claim data from the National Healthcare Insurance Service-National Health Screening Program in Korea. Included were people aged 20 or older who participated in the national health screening program at least once in the index year 2009 (n=9,950,548). Periodontitis was defined as diagnosed within 2 years before the index year according to ICD-10 code. We compared patients with periodontitis to individuals without periodontitis. The end point was newly diagnosed IBD that met both of ICD-10 codes and V code for rare intractable diseases until December 31th, 2017. We exclude IBD patients who were diagnosed within 1 year from the index year (lag period). Results The mean follow up duration was 7.26±0.76 years. Patients with periodontitis had higher risk of ulcerative colitis (UC) than populations without periodontitis matched by age, sex, smoking, drinking, physical activity and body mass index (hazard ratio [HR], 1.090; 95% confidence interval [CI], 1.022 to 1.162; p<0.0001). According to a subgroup analysis of the periodontitis group, the risk of UC was significantly higher in patients who were over 50 years old, heavy drinkers and current smokers (HR, 1.987; 95% CI, 1.123 to 3.515; p for interaction analysis=0.0331). However, the risk of CD in patients with periodontitis did not increase compared to the general population. Conclusions Patients with periodontitis are at an increased risk of UC compared with individuals without periodontitis. Patient with periodontitis who were current smoker had a higher risk of UC than smokers without periodontitis. [ABSTRACT FROM AUTHOR]

Background/Aims The association between atopic diseases and inflammatory bowel diseases (IBD) remains unclear. We conducted a nationwide population-based study to investigate the effect of atopic diseases on the development of IBD. Methods A total of 9,950,548 subjects who received medical check-up in 2009 were included and followed up until 2017. The presence of atopic diseases including atopic dermatitis (AD), allergic rhinitis (AR), and asthma were evaluated. Patients who developed IBD including Crohn's disease (CD) and ulcerative colitis (UC) were identified using the claims data from National Health Insurance. Results During a mean follow up of 7.3 years, 1,426 subjects (0.014%) developed CD and 5,916 subjects (0.059%) developed UC. The incidences of CD (per 100,000 person-years) were 4.088, 2.255, and 2.344, and the incidences of UC were 11.926, 9.857, and 9.377 in patients with AD, AR, and asthma, respectively. Multivariable analysis revealed that the adjusted hazard ratios (aHR) for incident CD in patients with AD, AR, and asthma were 2.21, 1.33, and 1.59 (95% confidence interval [CI]: 1.251 to 3.896, 1.152 to 1.532, and 1.186 to 2.123, respectively), while the risk for incident UC in patients in AD, AR, and asthma were 1.51, 1.32, and 1.28 (95% CI: 1.081 to 2.101, 1.235 to 1.416, and 1.110 to 1.484, respectively) compared to controls. Moreover, increase in the number of atopic diseases gradually increased the risk for CD and UC; CD showed aHR of 1.36 and 1.65 (95% CI: 1.180 to 1.571 and 1.143 to 2.370), and UC showed aHR of 1.30 and 1.49 (95% CI: 1.216 to 1.398 and 1.247 to 1.170) in one, and two or more atopic diseases, respectively. Conclusions Patients with atopic diseases showed increased association with IBD. [ABSTRACT FROM AUTHOR]

Background/Aims The incidence of inflammatory bowel disease (IBD) is increasing in Asian countries and numerous risk factors associated with the development of IBD have been studied. This study aims to demonstrate risk factors of Crohn's disease (CD) in South Korea and to specify any differences between age groups using the National Health Insurance Service (NHIS) database. Methods A total of 14,060,821 people over 40 years old who received a national health screening program in 2009 were followed up until December 2017. Patients with newly diagnosed CD were enrolled. CD was identified according to the International Classification of Diseases, 10th revision and the rare, intractable disease registration program codes from the NHIS dataset in South Korea. Results During the mean follow-up period of 7.39 years, a total of 1,337 (1.33 per 100,000) patients developed CD. In the middle age group (40 to 64 years old), patients with history of smoking (adjusted hazard ratio [aHR], 1.29; 95% confidence interval [CI], 1.06 to 1.58) and anemia (aHR, 1.99; 95% CI, 1.67 to 2.36) appeared to have significantly higher risk of developing CD. In the old age group (65 years old or older), ex-smoking and anemia also increased risk of CD (aHR, 1.58 [95% CI, 1.16 to 2.18]; aHR, 1.91 [95% CI, 1.53 to 2.38]; respectively). Especially in the middle age group, those with chronic kidney disease had statistically elevated risk of CD (aHR, 1.38; 95% CI, 1.06 to 1.79). Conclusions Ex-smokers and patients with anemia who are over 40 years old are at high risk of developing CD. In the middle age group in particular, chronic kidney disease patients were at higher risk of developing CD. People with potential risk factors need more cautious approach in monitoring CD. [ABSTRACT FROM AUTHOR]

Background/Aims The impact of proteinuria and its severity on the incidence of inflammatory bowel disease (IBD) has not been studied yet. We aimed to determine the association between proteinuria measured by urine dipstick test on the development of IBD. Methods This is a retrospective nationwide population-based study using the National Health Insurance Service (NHIS) database in South Korea. A total of 9,917,400 people aged 20 years or older who had undergone a national health examination conducted by NHIS in 2009 were followed up to 2017. The study population was classified into four groups according to the degree of proteinuria: negative, trace, 1+, and ≥2+. The primary endpoint was the newly diagnosed IBD, Crohn's disease (CD) or ulcerative colitis (UC) during follow- up period. Results Compared with the dipstick negative group, the risk of CD was significantly increased as the degree of proteinuria increased (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.01 [0.703 to 1.451], 1.515 [1.058 to 2.162], and 2.053 [1.301 to 3.24] in dipstick trace, 1+, and ≥2+ group, respectively), but there was no significant difference in the risk of UC (aHR with 95% CI, 1.12 [0.949 to 1.323], 0.947 [0.764 to 1.174], 1.009 [0.741 to 1.373]). Dipstick positive proteinuria increased the risk of CD regardless of subgroups. However, in the development of UC, dipstick positive proteinuria increased the risk of UC in those with diabetes mellitus (DM), but not in those without DM (aHR, 1.527 vs 0.846; interaction p-value 0.004). The risk of CD was increased or decreased according to changes in proteinuria but not associated with the risk of UC. Conclusions Proteinuria, measured by dipstick test, is strongly associated with the development of CD. [ABSTRACT FROM AUTHOR]