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Background: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. Methods: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. Results: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. Conclusions: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach. [ABSTRACT FROM AUTHOR]

Background: Corticosteroids are recommended only for induction of remission in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to evaluate the change in pharmacologic treatment use, particularly systemic corticosteroids, over approximately 30 years, and the impact of biologics on IBD treatment since their appearance in the 2000s. Methods: This retrospective study conducted in Japan used data from the Phoenix cohort database (January 1990 to March 2021). Patients with disease onset at age ≥ 10 years who received treatment for UC or CD between January 1990 and March 2021 were included. Outcome measures were change in IBD treatments used, total cumulative corticosteroid doses, initial corticosteroid dose, duration of corticosteroid treatment, and surgery rate. Results: A total of 1066 and 579 patients with UC and CD, respectively, were included. In UC, the rate of corticosteroid use as initial treatment was relatively stable regardless of the year of disease onset; however, in CD, its rate decreased in patients who had disease onset after 2006 (before 2006: 14.3–27.8% vs. after 2006: 6.6–10.5%). Compared with patients with disease onset before biologics became available, cumulative corticosteroid doses in both UC and CD, and the surgery rate in CD only, were lower in those with disease onset after biologics became available. Conclusions: Since biologics became available, corticosteroid use appears to have decreased, with more appropriate use. Furthermore, use of biologics may reduce surgery rates, particularly in patients with CD. UMIN Clinical Trials Registry; UMIN000035384. [ABSTRACT FROM AUTHOR]

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation. [ABSTRACT FROM AUTHOR]

Many molecular targeted agents, including biologics, have emerged for inflammatory bowel diseases (IBD), but their high prices have prevented their widespread use. This study aimed to reveal the changes in patient characteristics and the therapeutic strategies of IBD before and after the implementation of biologics in Japan, where the unique health insurance system allows patients with IBD and physicians to select drugs with minimum patient expenses. The analysis was performed using a prospective cohort, including IBD expert and nonexpert hospitals in Japan. In this study, patients were classified into two groups according to the year of diagnosis based on infliximab implementation as the prebiologic and biologic era groups. The characteristics of therapeutic strategies in both groups were evaluated using association analysis. This study analyzed 542 ulcerative colitis (UC) and 186 Crohn's disease (CD). The biologic era included 53.3% of patients with UC and 76.2% with CD, respectively. The age of UC (33.9 years vs. 38.8 years, P < 0.001) or CD diagnosis (24.3 years vs. 31.9 years, P < 0.001) was significantly higher in the biologic era group. The association analysis of patients with multiple drug usage histories revealed that patients in the prebiologic era group selected anti-tumor necrosis factor (TNF)-α agents, whereas those in the biologic era group preferred biologic agents with different mechanisms other than anti-TNF-α. In conclusion, this study demonstrated that both patient characteristics and treatment preferences in IBD have changed before and after biologic implementation. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) are recommended to receive the coronavirus disease 2019 (COVID-19) vaccine. However, a recent survey showed that patients with IBD are more hesitant to receive the vaccine than the general population. Detailed information on the side effects of the COVID-19 vaccine is necessary to encourage vaccination among patients with IBD. Aim: To investigate the frequency of side effects following COVID-19 vaccination in patients with IBD in Japan. Study design: a cross-sectional survey was conducted using a questionnaire administered to adult patients with IBD in a tertiary medical facility. Results: Among the participants who answered the questionnaire, 92.6%, 91.5%, and 41.5% of the participants had received their first, second, and third doses of the COVID-19 vaccine, respectively. Of the vaccinated participants, 88.3%, 86.3%, and 89.0% experienced side effects after receiving the first, second, and third doses of the vaccine, respectively. The incidences of fever, chills, and headaches were significantly higher among female participants than among male participants (p < 0.05). However, the frequencies of most side effects were comparable between the BNT162b2 mRNA and mRNA-1273 vaccines. Conclusion: The findings of our survey can help encourage patients with IBD to receive the COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn's disease (CD), is a risk factor for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE).Aim: To investigate the incidence of, and risk factors for, VTE in patients with IBD in Japan.Methods: This was a retrospective, non-interventional study in patients with IBD from the Japan Medical Data Center claims database. Incidence rates (IRs; unique patients with events per 100 patient-years) were calculated for VTE, DVT, and PE among the IBD, UC, and CD cohorts. Odds ratios of potential risk factors were calculated by univariate and multivariate analyses in a nested case-control design.Results: Overall, 16 273 patients with IBD were included: 13 585 with UC and 3443 with CD. VTE events occurred in 1.3%, 1.2%, and 1.9% of patients with IBD, UC, and CD, respectively. In patients with IBD, UC, and CD, IRs of VTE were 0.45, 0.40, and 0.64, respectively, IRs of DVT were 0.42, 0.38, and 0.61, respectively, and IRs of PE were 0.07, 0.07, and 0.11, respectively. In patients with IBD, treatment history (immunomodulators), cardiovascular risk (hypertension, high-density lipoprotein or diabetes mellitus, and history of coronary artery disease or heart failure), malignancy, and undergoing major surgery were identified as potential risk factors for VTE in the multivariate analysis, with similar risk factors reported for patients with UC and CD.Conclusions: This large study provides insight into the incidence and risk factors for VTE in patients with IBD from Japan. [ABSTRACT FROM AUTHOR]

Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. "Colitis microscopic" (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin. [ABSTRACT FROM AUTHOR]

Previous studies have shown that antibiotic use and enterocolitis increase the risk of developing inflammatory bowel disease (IBD) in western countries. However, these risk factors have not yet been identified in Asian populations. This study aimed to investigate the risk of IBD development associated with antibiotic use and enterocolitis in Japan. A Japanese health insurance claims database was used to identify patients recently diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) along with five matched participants without IBD. Episodes of antibiotic use and enterocolitis for 1 and 2 years before the date of diagnosis were analyzed using a conditional regression test. A total of 371 patients with CD and 2420 with UC were included. The adjusted odds ratio (AOR) increased in association with antibiotic use to 1.61 (95% confidence interval [CI] 1.26–2.05) and 1.20 (95% CI 1.09–1.31) and enterocolitis to 3.40 (95% CI 2.60–4.44) and 2.14 (95% CI 1.88–2.43) in 1 year in CD and UC, respectively. The risk associated with antibiotics was independent of the number or type of antibiotics, and the risk associated with enterocolitis did not differ with the pathogen that caused the disease. However, prior exposure to antibiotic use and enterocolitis was associated with an increased risk of developing IBD. [ABSTRACT FROM AUTHOR]

Background: The spread of coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide. The clinical background and clinical course of inflammatory bowel disease (IBD) among Japanese patients with COVID-19 remains unclear. Methods: This study is an observational cohort of Japanese IBD patients diagnosed with COVID-19. Data on age, sex, IBD (classification, treatment, and activity), COVID-19 symptoms and severity, and treatment of COVID-19 were analyzed. Results: From 72 participating facilities in Japan, 187 patients were registered from June 2020 to October 2021. The estimated incidence of COVID19 in Japanese IBD patients was 0.61%. The majority of IBD patients with COVID-19 (73%) were in clinical remission. According to the WHO classification regarding COVID-19 severity, 93% (172/184) of IBD patients had non-severe episodes, while 7% (12/184) were severe cases including serious conditions. 90.9% (165/187) of IBD patients with COVID-19 had no change in IBD disease activity. A logistic regression analysis stepwise method revealed that older age, higher body mass index (BMI), and steroid use were independent risk factors for COVID-19 severity. Six of nine patients who had COVID-19 after vaccination were receiving anti-tumor necrosis factor (TNF)-α antibodies. Conclusion: Age, BMI and steroid use were associated with COVID-19 severity in Japanese IBD patients. [ABSTRACT FROM AUTHOR]

Background: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. Aims: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. Methods: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. Results: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. Conclusion: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn's disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background and aim: After colectomy for ulcerative colitis (UC), very severe and sometimes lethal enteritis can develop. However, the clinical features remain uncertain because of the low incidence, diversity of symptoms, and undefined diagnostic criteria. The aim of this study was to define postoperative ulcerative colitis-related severe enteritis (UCRSE) and to investigate its clinical features. Methods: A retrospective multicenter study was performed as a survey of major medical facilities utilizing surgical supplies for inflammatory bowel disease in Japan from 2001 to 2014. UCRSE was defined as a case with massive intestinal bleeding, intestinal perforation, high-output stoma, and/or a requirement for medications, such as steroids and biologics. Patients with gastroduodenal lesions or pouchitis alone were excluded. The incidence, symptoms, involvement of bacteria, cytomegalovirus reactivation, treatment, and prognosis were examined for patients with UCRSE after colectomy. Results: Forty-two (0.8%) out of 5284 cases met the criteria for UCRSE. Major symptoms were massive intestinal bleeding (76.2%), which required a median of 3850 (560–18900) mL blood transfusion; high-output stoma (38.1%) with excretion of fluid of 5000 (2000–7800) mL/day; and intestinal perforation (7.1%). Hypovolemic shock (35.7%) and/or disseminated intravascular coagulation (31.0%) developed as serious complications. Tests for cytomegalovirus reactivation were positive in 26.2% of cases. The presence of pathogenic bacteria was confirmed in only 5 cases. Corticosteroids or infliximabs were effective in half of the patients. Thirteen cases (31.0%) were treated surgically and 22 cases (56.4%) required maintenance therapy. The mortality rate was 11.9%. Conclusion: UCRSE is a rare but serious complication after colectomy and is sometimes life-threatening. [ABSTRACT FROM AUTHOR]

Also, an Appendix listing iCREST-CD Study Group collaborators is included in this correction. Appendix: iCREST-CD Study Group Collaborators Masakazu Nagahori: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University; Tatsu Yukawa: Inflammatory Bowel Disease Center Yokohama City University Medical Center; Daisuke Saito: Department of Gastroenterology and Hepatology, Kyorin University School of Medicine; Mikio Kawai: Department of Intestinal Inflammation Research, Hyogo College of Medicine; Atsushi Masamune: Division of Gastroenterology, Tohoku University Graduate School of Medicine; Mitsuo Nagasaka: Department of Gastroenterology, Fujita Health University School of Medicine; Tomoe Kazama: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine. [Extracted from the article]

Background: IL12B is a promising candidate for a susceptibility gene in Crohn's disease (CD). The aim of this study was to perform a candidate gene analysis of IL12B in Japanese CD patients, investigate whether the genotype is associated with disease phenotypes, and determine how the risk allele affects susceptibility to CD.Methods: Three hundred seventy-five patients with CD, 265 patients with ulcerative colitis, and 463 healthy controls were examined. Ten single-nucleotide polymorphisms (SNPs) around IL12B were genotyped. Case-control and subphenotype (including disease course) analyses were performed. The allelic expression ratio of IL12B messenger RNA (mRNA) was examined by a SNaPshot analysis in lipopolysaccharide-stimulated monocytes.Results: Four SNPs located upstream of the IL12B gene were significantly associated with CD. A conditional analysis revealed that these associations included two independent signals tagged by IL12B_1 and IL12B_3 (P = 9.42 × 10-6 and  1.49 × 10-4 respectively). IL12B_3 was also associated with earlier relapse in CD (P = 0.0144). The allelic expression ratios of IL12B mRNA transcribed from the risk haplotype to the protective haplotype tagged by IL12B_3 in lipopolysaccharide-stimulated monocytes from ten healthy controls heterozygous for IL12B_3 were significantly higher than that of the respective genomic DNA (P = 0.00923). No SNP was associated with ulcerative colitis.Conclusions: We confirmed the association of SNPs located upstream of IL12B with CD in Japanese patients. The demonstrated allelic expression imbalance supports the idea that the IL12B risk haplotype confers susceptibility not only to CD onset but to also relapse through increased IL12B mRNA expression. [ABSTRACT FROM AUTHOR]

Background: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown cause that is characterized pathologically by an inflammatory and fibrotic process centered on the epithelium, leading to diffuse biliary stenosis and increased wall thickness throughout the intra- and extra-hepatic biliary trees. A nationwide survey in Japan revealed several differences in the clinical aspects of PSC between Japan and Western countries. PSC was recently designated an intractable hepatobiliary disease in Japan. The aim of this study was to establish Japanese diagnostic criteria for PSC according to the current Japanese conditions.Methods: The Intractable Hepato-Biliary Diseases Study Group in Japan of the Committee of Research on Measures for Intractable Diseases established a working group consisting of researchers specializing in PSC and proposed the 2016 Japanese diagnostic criteria for PSC.Results: The diagnostic criteria consisted of the major and minor items. Major items are directly related to bile duct changes based on biliary tract imaging and an increased alkaline phosphatase level. Minor items consist of an association with inflammatory bowel disease and liver histology.Conclusion: The diagnostic criteria for PSC are useful for general physicians in practice. [ABSTRACT FROM AUTHOR]

Background and Aim: There has been increased interest in sleep disorders in patients with inflammatory bowel disease (IBD). Studies in North America and Europe reported that the prevalence of restless legs syndrome (RLS) is much higher in patients with Crohn's disease (CD) than in the general population. The aim of this study was to reveal the prevalence and clinical features of RLS in Japanese patients with IBD and investigate the influence of RLS on sleep quality and quality of life (QOL).Methods: The study included 80 outpatients with IBD who visited Nagasaki University Hospital between December 2012 and July 2014. All patients completed the international RLS study group rating scale, a validated measure of the presence of RLS. Sleep quality was assessed using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI), and health-related QOL was assessed using the Japanese version of the 36-item short form healthy profile (SF-36) version 2.Results: The prevalence of RLS in patients with IBD was 20%, including rates of 21.7% in patients with ulcerative colitis (UC) and 17.6% in patients with CD. Among patients with CD, the proportion of women and serum level of CRP were higher in the RLS group than in the non-RLS group. Among those with UC, there were no differences in clinical characteristics between the RLS and non-RLS groups. Patients in the RLS group slept significantly less well than those in the non-RLS group (PSQI > 5; 62.5 vs. 34.4%, P < 0.05). No significant relationships were observed between QOL indices and the presence of RLS (SF-36 physical score, 46.8 vs. 50.1; mental score, 43.8 vs. 45.7; role/social score, 48.1 vs. 49.2).Conclusions: RLS occurs frequently in Japanese patients with UC as well as CD. RLS affects sleep quality but not QOL, and it should be considered one of the causes of sleep disturbance in patients with IBD. [ABSTRACT FROM AUTHOR]

Background: Although the incidence of inflammatory bowel diseases (IBD) in Japan has increased, the prevalence of celiac disease is considered very low with the lowest genetic disposition. IBD is reported as the most common comorbidity because of the high positive rate of serological celiac markers. The aim of this study was to examine the current incidence of celiac disease, especially in IBD patients in Japan, where both wheat consumption and incidence of IBD have increased. Methods: A total of 172 patients with IBD and 190 controls in Japan were screened for serum antibody of tissue transglutaminase and deaminated gliadin peptide. In sero-positive patients, HLA testing and upper gastrointestinal endoscopy with duodenal biopsy was performed. Some of the sero-positive patients started a gluten-restricted or unrestricted diet, and serological change was determined. Results: The positivity of both serum antibodies was significantly higher in IBD and correlated with disease activity. However, no biopsy-defined or HLA-defined true celiac disease was found. A decrease in serum antibody titers was observed with a gluten-restricted diet. Conclusions: Despite the increased incidence of IBD and high positivity for serum celiac antibody in Japanese IBD patients, no true-positive celiac disease was noted, suggesting the presence of gluten intolerance in these populations. [ABSTRACT FROM AUTHOR]

Background and Objectives: The sudden change in the dietary habits of the Japanese population towards a European/American-style diet since the 1960s is thought to be responsible for the recent increase in the incidence of inflammatory bowel disease (IBD) in Japan. Dietary fatty acid intake influences the fatty acid profiles of vital cell membranes, which might be a source of inflammatory mediators. Methods: We investigated the fatty acid composition of the erythrocyte membrane in 90 healthy Japanese and 43 initial-onset IBD patients (ulcerative colitis, UC: 25; Crohn's disease, CD: 18) who had not undergone any dietary intervention to examine the role fatty acids play in the onset of IBD. Results: The erythrocyte membrane n-3/ n-6 ratio of the initial-onset IBD patients was 0.42 ± 0.13, which was not significantly different from that of the healthy Japanese subjects (0.41 ± 0.13). However, the CD patients displayed a significantly lower mean percentage weight (MPW) of linoleic acid (LA) than the healthy subjects (8.25 ± 1.75 vs. 9.90 ± 1.29; p < 0.001), while their MPW of arachidonic acid (AA) was significantly higher than those of the healthy subjects and UC patients (11.22 ± 2.18 vs. 9.76 ± 1.64, p < 0.01; vs. 9.58 ± 1.97, p < 0.01, respectively). The mean delta 6-desaturation index of the CD patients was significantly higher than that of the healthy subjects (1.61 ± 0.65 vs. 1.11 ± 0.26; p < 0.001). Conclusions: The CD patients displayed significantly higher and lower MPW of AA and LA, respectively, than the healthy subjects, suggesting that delta 6-desaturase is hyperactivated in CD. The cell membrane fatty acid profile might be a therapeutic target in CD. [ABSTRACT FROM AUTHOR]

Purpose: Mesalazine and sulfasalazine are commonly used drugs for the treatment of inflammatory bowel disease. However, there have been few reports with a strict statistical analysis comparing the effects of mesalazine and sulfasalazine on laboratory test results. Therefore, we designed a retrospective cohort study to investigate whether or not differences in clinical laboratory parameters exist between mesalazine and sulfasalazine users. Methods: We used data from the Clinical Data Warehouse of Nihon University School of Medicine to identify cohorts of new mesalazine users ( n = 303) and sulfasalazine users ( n = 67). We used a multivariate regression model and regression adjustment with the propensity score to adjust for differences in baseline covariates between mesalazine and sulfasalazine users, and compared serum levels of creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and hematological parameters including red and white blood cell counts and platelet count. Results: After adjustment, in sulfasalazine users, the mean values for all tests showed no significant change between baseline and during the exposure period. In contrast, in mesalazine users, the mean WBC and platelet counts during the exposure period were significantly lower than those at baseline. Furthermore, mean serum urea nitrogen level during the exposure period was significantly higher than that at baseline. In terms of mean changes in laboratory test values during the exposure period compared with baseline, the reduction of platelet count in mesalazine users was significant in comparison to that in sulfasalazine users. Conclusion: Our findings suggested that the hematological adverse effects of mesalazine treatment might be greater than those of sulfasalazine treatment. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence of inflammatory bowel disease (IBD) is reported to have reached a plateau in Western countries, it is increasing in Asia. The etiology of IBD is still under investigation. We performed an epidemiological study to clarify the characteristics of IBD in Japan, focusing on patients' family history. Methods: We obtained clinical data on ulcerative colitis (UC) (46,114 cases) and Crohn's disease (CD) (11,305 cases) in 2007 from an electronic database maintained under the Japanese Ministry of Health, Labour and Welfare's nationwide registry system, and analyzed the differences in disease characteristics between patients with IBD who had a family history of the disease and those who did not. Results: A total of 2.7% of the patients with UC and 2.6% of those with CD had a family history. The present age and age at disease onset were lower among the patients with UC who had a family history than among those without (present age: p < 0.001; age at disease onset: p < 0.001; Mann-Whitney U-test), but no similar trend was observed in the patients with CD. Disease severity was worse among both the UC and CD patients with a family history. The clinical course of patients with UC was not affected by family history. Levels of independence in daily life were associated with family history among CD patients, whereas age was associated with levels of independence in daily life among UC patients. Conclusion: Disease characteristics of IBD vary in some aspects according to the presence or absence of a family history. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the complications of ulcerative colitis (UC) and the risk of cancer increases as the duration of the disease becomes longer. Surveillance colonoscopy has been considered to be important for the early detection and early treatment of colorectal cancer, especially in longstanding UC. Because it is not always easy to detect neoplastic lesions in UC endoscopically, guidelines recommend the use of step biopsy in surveillance, in which either 4 biopsy specimens for every 10 cm or a total of 33 or more biopsy specimens are obtained. However, it has been pointed out that a step biopsy obtaining several tens of biopsy specimens may not be an ideal method in terms of invasiveness to the patient or medical cost. Instead of step biopsy, recent studies report the usefulness of target biopsy, in which biopsy tissues are obtained only from regions suspected of neoplasia. Therefore, the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan has initiated a randomized controlled study to compare the efficacy of step biopsy and target biopsy. The present article gives an introduction to this ongoing randomized controlled trial in Japan. [ABSTRACT FROM AUTHOR]

Objective: We analyzed the database of the Japanese nationwide inflammatory bowel disease (IBD) registry, which was started in 1975, to characterize basic epidemiological and clinical features of childhood IBD, comparing them to those in adults. Study design: We analyzed the age of disease onset, disease severity and anatomical distribution in patients that were newly registered between 2003 and 2006 ( n = 2,940 for CD and 14,857 for UC). We also analyzed the current age, gender and family history of IBD of all patients filed in 2005, which included patients who were newly registered in 2005 and those who had been registered before 2005 and for whom an annual report had been received in 2005 (total number of subjects: 10,934 for CD and 37,846 for UC). Results: At the time of registration, 10.6% of CD and 5.9% of UC patients were ≤16 years old. In CD, the male to female ratio was 2.6 in adult- and 1.7 in childhood-onset patients ( P < 0.001). In UC, the male to female ratio was close to 1 in both age groups. In comparison with adults, pediatric patients more commonly had a positive family history for CD and UC ( P < 0.001), tended to have more severe disease at the time of registry ( P < 0.001 for CD, P < 0.05 for UC) and more often had extensive colitis in UC ( P < 0.001). Conclusion: The nationwide registry in Japan showed IBD in children has clinical features that are distinct from those in adults. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 × 10−12), a locus on chromosome 13q12 (rs17085007, P = 6.64 × 10−8) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 × 10−8). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis. [ABSTRACT FROM AUTHOR]

The Inflammatory Bowel Disease Questionnaire (IBDQ) is the most widely used disease-specific health-related quality of life questionnaire for patients with inflammatory bowel disease. However, little has been reported about the validation of IBDQ for patients with ulcerative colitis after surgery. The aim of this study was to assess the validity and reliability of the Japanese version of IBDQ in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis (IPAA). The validity and reliability of the Japanese IBDQ were assessed in patients with ulcerative colitis who had received IPAA in our hospital. We mailed them the Japanese IBDQ and a supplemental questionnaire on bowel function, which was developed at our institution. Internal consistency, discriminative validity, and factor validity were assessed. Of the 121 patients to whom we sent the questionnaires, 64 patients (53%) participated in this study. The Japanese IBDQ scores correlated well with Cronbach's alpha value (0.800 to 0.923) and daily life satisfaction score (Pearson's r, 0.492 to 0.700). The total IBDQ score and two subscale scores of the IBDQ, “bowel symptoms” and “systemic symptoms,” correlated well with daily bowel-movement frequency (Pearson's r, −0.256 to −0.329). Factor analysis revealed a four-factor structure, and all correlations among factors were moderately positive (0.337 to 0.465). Although the factor distribution was not clearly divided into the four IBDQ subscales, these four factors showed a marked tendency to represent the IBDQ subscales independently. The Japanese IBDQ is a valid and reliable instrument for the assessment of Japanese patients with ulcerative colitis after IPAA. [ABSTRACT FROM AUTHOR]

Chronic inflammatory bowel diseases (IBDs), specifically Crohn's disease (CD) and ulcerative colitis (UC), have increased significantly in western countries and Japan over the last decade, but very little is known about their pathogenesis. A candidate-gene approach recently identified NOD2/CARD15 as one susceptibility gene from the IBD1 locus on chromosome 16. Alterations in this gene were found in many Caucasian patients with CD; in particular, two nonsynonymous substitutions (R702W and G908R) and a frameshift mutation (1007fs) were shown to be independent risk factors for CD. We investigated DNA from 483 Japanese CD patients to detect those three mutations in NOD2/CARD15 by appropriate genotyping techniques, but found only an R702Q substitution in a single patient. Direct sequencing of DNA from 96 of our patients in the regions containing the three reported major mutations detected no sequence alterations of consequence. Our findings indicate that the NOD2/CARD15 gene is not a major contributor to CD susceptibility in the Japanese population. [ABSTRACT FROM AUTHOR]

Presents a summary of the International Symposium entitled "State-of-the-Art Work in Immunological Research for IBD Therapy" at the 88th annual meeting of the Japanese Society of Gastroenterology in Asahikawa, Japan. Concern about the increasing number of inflammatory bowel disease (IBD) patients; Lectures presented on the present and future therapy against the disease; Educational experience and useful information provided by the symposium to young researchers for their research work on IBD.