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Background: ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis., Objectives: To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features., Methods: Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (OR P ) and 95% CI were calculated under the random effects model., Results: Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (OR P : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (OR P : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (OR P : 1.21, 95% CI: 1.07-1.38, p-value: 0.003)., Conclusions: ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

While differential antibody responses SARS-CoV-2 in patients with inflammatory bowel disease (IBD) receiving infliximab and vedolizumab are well-characterized, the immune pathways underlying these differences remain unknown. Prior to COVID-19 vaccine development, we screened 235 patients with IBD receiving biological therapy for antibodies to SARS-CoV-2 and measured serum cytokines. In seropositive patients, we prospectively collected clinical data. We found a cytokine signature in patients receiving vedolizumab who are seropositive compared with seronegative for SARS-CoV-2 antibodies that may be linked to repeated SARS-CoV-2 infections. However, there were no differences between seropositive and seronegative patients receiving infliximab. In this single-center cohort of patients with IBD with anti-SARS-CoV-2 antibodies at the onset of the COVID-19 pandemic, and therefore without influence of vaccination, there is a cytokine signature in patients receiving vedolizumab but not infliximab. These findings lay the groundwork for further studies on immune consequences of viral infection in patients with IBD, which is postulated to evolve from aberrant host-microbe responses., (© 2024. The Author(s).)

Background: Beyond systematic reviews and meta-analyses, there have been no direct studies of serological response to COVID-19 in patients with inflammatory bowel disease (IBD) across continents. In particular, there has been limited data from Asia, with no data reported from India. The ICARUS-IBD (International study of COVID-19 Antibody Response Under Sustained immunosuppression in IBD) consortium assessed serological response to SARS-CoV-2 in patients with IBD in North America, Europe, and Asia., Methods: The ICARUS-IBD study is a multicenter observational cohort study spanning sites in 7 countries. We report seroprevalence data from 2303 patients with IBD before COVID-19 vaccination between May 2020 and November 2021. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies were analyzed., Results: The highest and lowest SARS-CoV-2 anti-spike seropositivity rates were found in Asia (81.2% in Chandigarh and 57.9% in Delhi, India; and 0% in Hong Kong). By multivariable analysis, country (India: odds ratio [OR], 18.01; 95% confidence interval [CI], 12.03-26.95; P < .0001; United Kingdom: OR, 2.43; 95% CI, 1.58-3.72; P < .0001; United States: OR, 2.21; 95% CI, 1.27-3.85; P = .005), male sex (OR, 1.46; 95% CI, 1.07-1.99; P = .016), and diabetes (OR, 2.37; 95% CI, 1.04-5.46; P = .039) conferred higher seropositivity rates. Biological therapies associated with lower seroprevalence (OR, 0.22; 95% CI, 0.15-0.33; P < .0001). Multiple linear regression showed associations between anti-spike and anti-nucleocapsid titers with medications (P < .0001) but not with country (P = .3841)., Conclusions: While the effects of medications on anti-SARS-CoV-2 antibody titers in patients with IBD were consistent across sites, geographical location conferred the highest risk of susceptibility to serologically detectable SARS-CoV-2 infection. Over half of IBD patients in India were seropositive prior to vaccination. These insights can help to inform shielding advice, therapeutic choices, and vaccine strategies in IBD patients for COVID-19 and future viral challenges., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Quality of life (QoL) in children with inflammatory bowel disease (IBD) is often impaired by underlying disease. We evaluated factors affecting health-related QoL (HRQoL) in Malaysian children with IBD., Methods: A cross-sectional study using IMPACT-III questionnaires evaluating HRQoL in children aged 8-17 years with duration of IBD of ≥6 months was conducted. IMPACT-III, a validated instrument designed to measure HRQoL in children with IBD, was used. Higher IMPACT-III (maximum = 100) score indicates better HRQoL. Impact of socio-demographic and clinical factors of IBD on the HRQoL was evaluated. Paediatric Crohn's disease (CD) and ulcerative colitis (UC) activity indices were used to classify disease severity., Results: A total of 75 children (UC = 44, CD = 41; mean (SD) age at diagnosis 8.2 (3.5) years) were interviewed at mean age of 12.8 (2.7) years. Mean IMPACT-III score was significantly lower in children with more severe disease (mild: 71.8 (13.6) vs. moderate: 65.5 (10.9) vs. severe: 46.3 (14.5); P < 0.001), history of hospitalisation (yes: 64.0 (14.0) vs. none: 74.1 (12.2), P = 0.034) and a higher number of admissions (r = -0.352, P = 0.041) in preceding 6 months. Diagnosis at a younger age (r = -0.31, P = 0.007) and a longer duration of disease (r = 0.286, P = 0.013) was associated with higher score. A higher weight-for-age (r = 0.261, P = 0.023) or body mass index-for-age z-score (r = 0.235, P = 0.042) was correlated with a better body image domain score, respectively., Conclusions: In Malaysian children with IBD, HRQoL was adversely affected by a more severe disease. Better control of disease activity and maintaining long-term remission are important to improve the HRQoL in childhood IBD., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Aim: Early-life environmental exposure, which has important implications in the pathogenesis of inflammatory bowel disease (IBD), is not well understood in Asian children. We examined environmental factors prior to the development of childhood IBD in a Southeast Asian population., Methods: We conducted a case control study in IBD diagnosed before 18 years of age and controls matched by gender, age and ethnicity. A questionnaire recording medical, family, dietary and social histories, home environment, childhood diseases and immunisation status was used., Results: In a multivariate analysis involving 70 children with IBD (Crohn's disease (CD) = 38; ulcerative colitis (UC) = 32) and 140 controls, childhood acute gastroenteritis (odds ratio (OR): IBD 6.9; CD 7.8; UC 5.8) and excessive antibiotic usage in early childhood (OR: IBD 5.3; CD 4.2; UC 4.8) were significantly associated with IBD, CD and UC. Having a fish or turtle aquarium (OR 6.0), major stressful life events (OR 5.6) and attending the same school concurrently with a sibling (OR 2.9) were significant risk factors for IBD. Duration of breastfeeding >6 months (OR: IBD 0.4; UC 0.2) and safe water consumption (OR: IBD 0.2; UC 0.2) reduced the odds of having IBD and UC, respectively. Being vaccinated for rotavirus reduced the odds of developing IBD (OR 0.1)., Conclusions: Several risk and protective factors were identified in this environmental risk study in Southeast Asian children with IBD. This knowledge has important implications in understanding disease aetiology and future prevention strategies to reduce the development of IBD in Southeast Asian children., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background and Aim: Inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory conditions comprising two major subtypes: Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is increasing in Asian countries including Malaysia. The aim of this study was to determine whether 32 single nucleotide polymorphisms (SNPs) strongly associated with IBD from genome-wide association studies, performed mainly in Caucasian populations, are associated with IBD in a Malaysian population, correlating these findings with local and systemic inflammation., Methods: Selected SNPs were investigated in a Malaysian cohort comprising 36 IBD patients and 75 controls using customized matrix-assisted laser desorption ionization time-of-flight genotyping. Local mRNA and/or systemic protein levels of IL-10, IL-12, IL-22, IL-23, and TNF-α were measured in these same subjects., Results: ATG16L2 rs11235667 and LINC00824 rs6651252 was significantly associated with increased CD risk while IL12B rs56167332 was a significant protective factor. Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor. After adjusting for age, gender, and ethnicity, SBNO2 rs2024092, ATG16L2 rs11235667, CARD9 rs10781499, and LINC00824 rs6651252 remained associated with IBD. Interestingly, the risk alleles of IL10 rs3024505, CARD9 rs1078149, and IL12 rs6556412 were associated with higher levels of IL-10, IL-22, and IL-23 in these same subjects, respectively., Conclusions: This study identified eight SNPs associated with IBD and/or its subtypes in the Malaysia population, significantly advancing our understanding of the genetic contribution to IBD in this understudied population. Three of these SNPs modulated relevant cytokine levels and thus, may directly contribute to IBD pathogenesis., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Since the beginning of the pandemic, patients with inflammatory bowel diseases [IBD] have been considered at high risk for infection and complications of COVID-19. IBD patients and patients taking immunosuppressive therapy were excluded from clinical phase III vaccine trials, complicating the assessment of effectiveness of these new vaccines. From past experience we know that adapted vaccination strategies may be appropriate in some IBD patients to optimise immunogenicity. We review current evidence on SARS-CoV-2 vaccination relevant to IBD patients, including immune responses from humoral to cellular, emerging data on new variants, and off-label vaccination schemes. We also identify clinical and scientific knowledge gaps that can be translated into both large-scale population-based studies and targeted vaccine studies to describe the precise immune responses induced by SARS-CoV-2 vaccines in IBD patients. We strongly endorse the recommendation of vaccinating IBD patients to ensure maximal protection from COVID-19 both for the individual and the community., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Current knowledge on the clinical features and natural history of childhood primary sclerosing cholangitis - inflammatory bowel disease in Asia is limited. We described the presenting features and natural history of primary sclerosing cholangitis-inflammatory bowel disease seen in a cohort of Southeast Asian children., Methods: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia., Results: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived., Conclusions: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease., (Copyright © 2018. Published by Elsevier B.V.)

Competing Interests: The authors have declared that no competing interests exist.