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Shenoy S, Jena A, Levinson C, Sharma V, Deepak P, Aswani-Omprakash T, Sebastian S, Colombel JF, Agrawal M. Inflammatory bowel disease in south Asia: a scoping review. Lancet Gastroenterol Hepatol 2025; 10:259-274. [PMID: 39954693 DOI: 10.1016/s2468-1253(24)00341-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 09/27/2024] [Accepted: 10/02/2024] [Indexed: 02/17/2025]
Abstract
Inflammatory bowel disease (IBD) is rising at an alarming rate in south Asia and there is a paucity of data on IBD in this region. For this scoping review, we conducted a systematic search to identify all observational and interventional studies on IBD in south Asia. Of 14 924 potentially eligible studies, 524 were included in this scoping review and summarised under the domains of epidemiology, natural history, phenotype and comorbid conditions, therapeutics, and psychosocial health. According to the literature, IBD incidence and prevalence are rising in south Asia and among south Asian immigrants, and the diagnostic rate is higher in men than in women. Genetic predisposition is an important risk factor in south Asia, whereas environmental risk factors are less clear. Delay in diagnosis, although possibly decreasing over time, is common in south Asia and is associated with worse outcomes. There are no clear differences in IBD phenotype and severity in south Asia relative to Europe and North America. Corticosteroids and immunomodulators are the mainstay of treatment in south Asia whereas the use of biologics is less common. Mental health disorders, malnutrition, and reduced quality of life are prevalent in patients with IBD in south Asia, and the use of complementary and alternative medicines among patients is an important consideration. Key knowledge gaps include the paucity of data from countries other than India, prospective, long-term, follow-up studies, and clinical drug trials in south Asia. IBD is a growing challenge in this region and warrants urgent clinical interventions, research, resource allocation, and health policy implementation.
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Affiliation(s)
- Shabari Shenoy
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; South Asian IBD Alliance, New York, NY, USA
| | - Anuraag Jena
- Department of Gastroenterology, Institute of Medical Sciences and Sum Hospital, Bhubaneswar, India; South Asian IBD Alliance, New York, NY, USA
| | - Carrie Levinson
- Gustave L and Janet W Levy Library, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Parakkal Deepak
- Division of Gastroenterology, Washington University School of Medicine in St Louis, St Louis, MO, USA; South Asian IBD Alliance, New York, NY, USA
| | | | - Shaji Sebastian
- South Asian IBD Alliance, New York, NY, USA; IBD Unit, Hull University Teaching Hospitals, Hull, UK
| | - Jean-Frederic Colombel
- The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Manasi Agrawal
- The Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Environmental Health and Climate Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA; South Asian IBD Alliance, New York, NY, USA; Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
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Swaminathan A, Day AS, Sparrow MP, Peyrin-Biroulet L, Siegel CA, Gearry RB. Review article: Measuring disease severity in inflammatory bowel disease - Beyond treat to target. Aliment Pharmacol Ther 2024; 60:1176-1199. [PMID: 39403053 DOI: 10.1111/apt.18231] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/07/2024] [Accepted: 08/18/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this. METHODS To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD. RESULTS Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient. CONCLUSIONS Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.
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Affiliation(s)
- Akhilesh Swaminathan
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health and School of Translational Medicine, Monash University, Australia
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoevre-les-Nancy, France
- Department of Gastroenterology, INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandoeuvre-les-Nancy, France
- Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Corey A Siegel
- Center for Digestive Health, Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Centre, Lebanon, New Hampshire, USA
| | - Richard B Gearry
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
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Dou Z, Zheng H, Shi Y, Li Y, Jia J. Analysis of global prevalence, DALY and trends of inflammatory bowel disease and their correlations with sociodemographic index: Data from 1990 to 2019. Autoimmun Rev 2024; 23:103655. [PMID: 39366514 DOI: 10.1016/j.autrev.2024.103655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 09/11/2024] [Accepted: 09/29/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a kind of chronic inflammatory disorders of the gastrointestinal tract with diverse prevalence rates and patterns globally. Accurate comprehension of the disease's epidemiological characteristics is imperative for disease control and prevention all over the world. OBJECTIVE To provide the most updated estimates on the global burden of IBD using the 2019 Global Burden of Disease (GBD) study data, to systematically analyze the IBD epidemiological characteristics at the global, regional, and national levels including the prevalence, incidence, and disability-adjusted life years (DALY) rates, and to analyze the correlations of the socioeconomic development level with IBD epidemiological characteristics. METHODS We conducted an overall analysis of the global, regional, and national burden of IBD from 1990 to 2019, data from the 2019 GBD study. The GBD's classification of the world into 21 regions and 204 countries and territories facilitated a thorough examination. Age-standardized estimated annual percentage changes (EAPCs) were computed to assess the temporal trends in IBD age-standardized rates (ASRs), with age standardization employed to mitigate potential confounding effects from age structure. The sociodemographic Index (SDI) was used to correlate the socioeconomic development level with the epidemiological characteristics of IBD. RESULTS From 1990 to 2019, the global age-standardized prevalence, incidence, and DALY rates of IBD remained high. There was a slight downward trend in the global age-standardized incidence and DALY rates of IBD and men exhibited higher DALY rates than women. In 2019, high-income North America recorded the highest age-standardized prevalence, incidence, and DALY rates, while Oceania had the lowest age-standardized prevalence and incidence rates. South Asia had the lowest age-standardized DALY rates. The age-standardized mortality and DALY rates decreased as SDI values increased and remained higher than the expected levels over the past three decades. A negative correlation was observed between age-standardized DALY rates and SDI at the national level. CONCLUSIONS This analysis of the GBD 2019 database demonstrates that the overall global burden of IBD is still high. Meanwhile, an increasing disease burden is observed in the middle and low SDI locations.
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Affiliation(s)
- Zhili Dou
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, PR China; Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, PR China
| | - Huiling Zheng
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, PR China
| | - Yanyan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, PR China.
| | - Yuan Li
- Department of Gastroenterology, Peking University International Hospital, Beijing 102206, PR China.
| | - Jinzhu Jia
- Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, PR China; Center for Statistical Science, Peking University, Beijing 100191, PR China.
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Weng MT, Hsiung CY, Wei SC, Chen Y. Nanotechnology for Targeted Inflammatory Bowel Disease Therapy: Challenges and Opportunities. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2024; 16:e1999. [PMID: 39439396 DOI: 10.1002/wnan.1999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 09/13/2024] [Indexed: 10/25/2024]
Abstract
Inflammatory bowel disease (IBD) is a complex and recurring inflammatory disorder that affects the gastrointestinal tract and is influenced by genetic predisposition, immune dysregulation, the gut microbiota, and environmental factors. Advanced therapies, such as biologics and small molecules, target diverse immune pathways to manage IBD. Nanoparticle (NP)-based drugs have emerged as effective tools, offering controlled drug release and targeted delivery. This review highlights NP modifications for anti-inflammatory purposes, utilizing changes such as those in size, charge, redox reactions, and ligand-receptor interactions in drug delivery systems. By using pathological and microenvironmental cues to guide NP design, precise targeting can be achieved. In IBD, a crucial aspect of NP intervention is targeting specific types of cells, such as immune and epithelial cells, to address compromised intestinal barrier function and reduce overactive immune responses. This review also addresses current challenges and future prospects, with the goal of advancing the development of NP-mediated strategies for IBD treatment.
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Affiliation(s)
- Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chia-Yueh Hsiung
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yunching Chen
- Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan
- Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan
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Yen HH, Wu JF, Wang HY, Chang TA, Chang CH, Chang CW, Chao TH, Chou JW, Chou YH, Chuang CH, Hsu WH, Hsu TC, Huang TY, Hung TI, Le PH, Lin CC, Lin CC, Lin CP, Lin JK, Lin WC, Ni YH, Shieh MJ, Shih IL, Shun CT, Tsai TJ, Wang CY, Weng MT, Wong JM, Wu DC, Wei SC. Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023. Intest Res 2024; 22:213-249. [PMID: 39099217 PMCID: PMC11309818 DOI: 10.5217/ir.2023.00050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 04/25/2024] [Accepted: 04/29/2024] [Indexed: 08/06/2024] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.
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Affiliation(s)
- Hsu-Heng Yen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Ting-An Chang
- Department of Pathology, Taipei City Hospital, Renai-Branch, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Te-Hsin Chao
- Division of Colon and Rectal Surgery, Department of Surgery, Chiayi and Wangiao Branch, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jen-Wei Chou
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, MacKay Memorial Hospital, MacKay Medical College, Taipei, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tsung-I Hung
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Chun-Che Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Pin Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Chen Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University College of Medicine and Children’s Hospital, Taipei, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - I-Lun Shih
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Pathology, Good Liver Clinic, Taipei, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Wu JF, Yen HH, Wang HY, Chang TA, Chang CH, Chang CW, Chao TH, Chou JW, Chou YH, Chuang CH, Hsu WH, Hsu TC, Huang TY, Hung TI, Le PH, Lin CC, Lin CC, Lin CP, Lin JK, Lin WC, Ni YH, Shieh MJ, Shih IL, Shun CT, Tsai TJ, Wang CY, Weng MT, Wong JM, Wu DC, Wei SC. Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease updated in 2023. Intest Res 2024; 22:250-285. [PMID: 39099218 PMCID: PMC11309825 DOI: 10.5217/ir.2024.00060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 06/06/2024] [Accepted: 06/13/2024] [Indexed: 08/06/2024] Open
Abstract
Crohn's disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.
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Affiliation(s)
- Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Department of Post-Baccalaureate Medicine, National Chung Hsing University College of Medicine, Taichung, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Ting-An Chang
- Department of Pathology, Taipei City Hospital, Renai-Branch, Taipei, Taiwan
| | - Chung-Hsin Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
- MacKay Medical College, Taipei, Taiwan
| | - Te-Hsin Chao
- Division of Colon and Rectal Surgery, Department of Surgery, Chiayi and Wangiao Branch, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jen-Wei Chou
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, MacKay Memorial Hospital, MacKay Medical College, Taipei, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tsung-I Hung
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Chang Gung Microbiota Therapy Center, Linkou Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| | - Chun-Che Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taipei, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Pin Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taipei, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Surgery, Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wei-Chen Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Children’s Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - I-Lun Shih
- Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Pathology, Good Liver Clinic, Taipei, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan
- Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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7
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Williamson KA, Yun M, Koster MJ, Arment C, Patnaik A, Chang TW, Bledsoe AC, Sae-Tia S, Shah AS, Samuels J, Davis JM, Yao Q. Susceptibility of nucleotide-binding oligomerization domain 2 mutations to Whipple's disease. Rheumatology (Oxford) 2024; 63:1291-1296. [PMID: 37467078 DOI: 10.1093/rheumatology/kead372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/13/2023] [Accepted: 06/30/2023] [Indexed: 07/21/2023] Open
Abstract
OBJECTIVES Whipple's disease (WD) results from infection of the bacteria Tropheryma whipplei (TW). This disease is characterized by macrophage infiltration of intestinal mucosa and primarily affects Caucasian males. Genetic studies of host susceptibility are scarce. Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is an innate immune sensor, resides mainly in monocytes/macrophages and contributes to defence against infection and inflammatory regulation. NOD2 mutations are associated with autoinflammatory diseases. We report the association of NOD2 mutations with TW and WD for the first time. METHODS A multicentre, retrospective study of three patients with WD was conducted. Patients received extensive multidisciplinary evaluations and were cared for by the authors. NOD2 and its association with infection and inflammation were schematically represented. RESULTS All patients were Caucasian men and presented with years of autoinflammatory phenotypes, including recurrent fever, rash, inflammatory arthritis, gastrointestinal symptoms and elevated inflammatory markers. All patients underwent molecular testing using a gene panel for periodic fever syndromes and were identified to carry NOD2 mutations associated with NOD2-associated autoinflammatory disease. Despite initially negative gastrointestinal evaluations, repeat endoscopy with duodenal tissue biopsy ultimately confirmed WD. After initial ceftriaxone and maintenance with doxycycline and/or HCQ, symptoms were largely controlled, though mild relapses occurred in follow-up. CONCLUSION Both NOD2 and TW/WD are intensively involved in monocytes/macrophages. WD is regarded as a macrophage disease. NOD2 leucin-rich repeat-associated mutations in monocytes/macrophages cause functional impairment of these cells and consequently may make the host susceptible for TW infection and WD, especially in the setting of immunosuppression.
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Affiliation(s)
| | - Mark Yun
- Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA
| | | | | | - Asha Patnaik
- Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA
| | - Tara W Chang
- Pathology, Boston Scientific, Alpharetta, GA, USA
| | - Adam C Bledsoe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Sutthichai Sae-Tia
- Division of Infectious Disease, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA
| | - Aditya S Shah
- Division of Public Health, Infectious Diseases and Occupational Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - John M Davis
- Division of Rheumatology, Mayo Clinic, Rochester, MN, USA
| | - Qingping Yao
- Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA
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8
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Nakajo K, Yamazaki M, Chung H, Xu Y, Qiu H. Trends in the prevalence and incidence of Crohn's disease in Japan and the United States. Int J Colorectal Dis 2024; 39:61. [PMID: 38676760 PMCID: PMC11055788 DOI: 10.1007/s00384-024-04636-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/19/2024] [Indexed: 04/29/2024]
Abstract
PURPOSE This study is to describe patient demographic characteristics and estimate annual prevalence and incidence rates of Crohn's disease (CD) in Japan and the United States (US). METHODS Two large employment-based healthcare claims databases (Japan Medical Data Center [JMDC] in Japan and Merative MarketScan [Merative] in the US) were used to identify patients with CD from 2010 to 2019. Cases were confirmed using an algorithm based on diagnostic with/without treatment codes. The Merative population was used for sex and age standardization of annual prevalence and incidence rates estimated from the JMDC. RESULTS Patients with CD were generally younger in Japan than in the US at diagnosis (mean 33.6 vs. 39.4 years) and 71.5% were male versus 45.1% in the US. Annual prevalence per 100,000 population increased substantially in both countries, from 34.2 in 2010 to 54.5 in 2019 in Japan (standardized) and 163.3 to 224.2 in the US. Prevalence rates increased in both males and females in all age groups between 6 and < 65 years. Annual incidence rate per 100,000 person-years was almost fourfold higher in the US than Japan (21.0 vs. 5.5 [standardized] in 2019) but remained stable in both countries over time in both sexes and in all age groups. CONCLUSION The epidemiology of CD differs between Japan and the US. Research to understand the basis of these differences could help to identify at-risk groups in each country, and guide implementation of preventive measures.
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Affiliation(s)
- Ko Nakajo
- Global Epidemiology, Office of the Chief Medical Officer, Janssen Research & Development, LLC, Tokyo, Japan
| | - Michiyo Yamazaki
- Global Epidemiology, Office of the Chief Medical Officer, Janssen Research & Development, LLC, Titusville, USA
| | - Hsingwen Chung
- Global Epidemiology, Office of the Chief Medical Officer, Janssen Research & Development, LLC, Titusville, USA
| | - Youran Xu
- Global Epidemiology, Office of the Chief Medical Officer, Janssen Research & Development, LLC, Beijing, China
| | - Hong Qiu
- Global Epidemiology, Office of the Chief Medical Officer, Janssen Research & Development, LLC, Titusville, USA.
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9
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Venkateswaran N, Sultan K. Racial and ethnic disparities in clinical presentation, management, and outcomes of patients with inflammatory bowel disease: a narrative review. Transl Gastroenterol Hepatol 2024; 9:28. [PMID: 38716206 PMCID: PMC11074478 DOI: 10.21037/tgh-23-43] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Accepted: 03/11/2024] [Indexed: 02/05/2025] Open
Abstract
BACKGROUND AND OBJECTIVE Inflammatory bowel disease (IBD) is a chronic condition that has been increasing in prevalence and incidence worldwide. Although, most cases are described in Caucasian populations, there has been a rise in IBD diagnosis among other populations. In this article, we will discuss the disparities in the presentation, management, medical and surgical outcomes of IBD patients among different racial and ethnic groups. METHODS A literature search was conducted in PubMed, Medline, and Google Scholar. The search strategy included targeted keywords to identify specific studies that provided the current literature on disparities in IBD presentation and management. Articles for presentation were selected by the authors, in accordance with a narrative review format, favoring population-based studies, systematic reviews and meta-analysis over single or multicenter reports. KEY CONTENT AND FINDINGS Epidemiological data has shown that there is an increasing incidence in IBD diagnosis among Black, Asian, and Hispanic populations over the past decade. Differences in genetic predispositions have been observed, however it is difficult to ascertain if the minor differences in presentation and medical/surgical management reported are due to innate differences or due to confounding factors such as access to health care. CONCLUSIONS Differences in genetic predisposition, and clinical presentation have been observed to exist among IBD non-Caucasian populations. There were also differences observed in both surgical and medical management, but it is difficult to ascertain if these were innate differences or due to societal factors.
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Affiliation(s)
- Niranjani Venkateswaran
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Northshore/Hofstra Zucker School of Medicine, Manhasset, NY, USA
| | - Keith Sultan
- Inflammatory Bowel Disease Center, Department of Gastroenterology, Northshore/Hofstra Zucker School of Medicine, Manhasset, NY, USA
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10
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Collen LV, Snapper SB. Response to Letter to the Editor: "Failure Rate of Antitumor Necrosis Factor Alpha Biologics in Very Early Onset Inflammatory Bowel Disease". Inflamm Bowel Dis 2024; 30:513-514. [PMID: 38206353 PMCID: PMC10906351 DOI: 10.1093/ibd/izad317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Affiliation(s)
- Lauren V Collen
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Scott B Snapper
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA
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11
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Jia K, Shen J. Transcriptome-wide association studies associated with Crohn's disease: challenges and perspectives. Cell Biosci 2024; 14:29. [PMID: 38403629 PMCID: PMC10895848 DOI: 10.1186/s13578-024-01204-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 02/04/2024] [Indexed: 02/27/2024] Open
Abstract
Crohn's disease (CD) is regarded as a lifelong progressive disease affecting all segments of the intestinal tract and multiple organs. Based on genome-wide association studies (GWAS) and gene expression data, transcriptome-wide association studies (TWAS) can help identify susceptibility genes associated with pathogenesis and disease behavior. In this review, we overview seven reported TWASs of CD, summarize their study designs, and discuss the key methods and steps used in TWAS, which affect the prioritization of susceptibility genes. This article summarized the screening of tissue-specific susceptibility genes for CD, and discussed the reported potential pathological mechanisms of overlapping susceptibility genes related to CD in a certain tissue type. We observed that ileal lipid-related metabolism and colonic extracellular vesicles may be involved in the pathogenesis of CD by performing GO pathway enrichment analysis for susceptibility genes. We further pointed the low reproducibility of TWAS associated with CD and discussed the reasons for these issues, strategies for solving them. In the future, more TWAS are needed to be designed into large-scale, unified cohorts, unified analysis pipelines, and fully classified databases of expression trait loci.
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Affiliation(s)
- Keyu Jia
- Laboratory of Medicine, Baoshan Branch, Ren Ji Hospital, School of Medicine, Nephrology department, Shanghai Jiao Tong University, 1058 Huanzhen Northroad, Shanghai, 200444, China
| | - Jun Shen
- Laboratory of Medicine, Baoshan Branch, Ren Ji Hospital, School of Medicine, Nephrology department, Shanghai Jiao Tong University, 1058 Huanzhen Northroad, Shanghai, 200444, China.
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Research Center, Ren Ji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Shanghai, China.
- NHC Key Laboratory of Digestive Diseases, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
- Division of Gastroenterology and Hepatology, Baoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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12
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Mishra Y, Mishra V, Aljabali AAA, El-Tanani M, Naikoo GA, Charbe N, Chava SR, Tambuwala MM. 3D Printed Personalized Colon-targeted Tablets: A Novel Approach in Ulcerative Colitis Management. Curr Drug Deliv 2024; 21:1211-1225. [PMID: 37718525 DOI: 10.2174/1567201821666230915150544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 07/19/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are two types of idiopathic inflammatory bowel disease (IBD) that are increasing in frequency and incidence worldwide, particularly in highly industrialized countries. Conventional tablets struggle to effectively deliver anti-inflammatory drugs since the inflammation is localized in different areas of the colon in each patient. The goal of 3D printing technology in pharmaceutics is to create personalized drug delivery systems (DDS) that are tailored to each individual's specific needs. This review provides an overview of existing 3D printing processes, with a focus on extrusion-based technologies, which have received the most attention. Personalized pharmaceutical products offer numerous benefits to patients worldwide, and 3D printing technology is becoming more affordable every day. Custom manufacturing of 3D printed tablets provides innovative ideas for developing a tailored colon DDS. In the future, 3D printing could be used to manufacture personalized tablets for UC patients based on the location of inflammation in the colon, resulting in improved therapeutic outcomes and a better quality of life.
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Affiliation(s)
- Yachana Mishra
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara (Punjab)-144411, India
| | - Vijay Mishra
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara (Punjab)-144411, India
| | - Alaa A A Aljabali
- Faculty of Pharmacy, Department of Pharmaceutics & Pharmaceutical Technology, Yarmouk University, Irbid 21163, Jordan
| | - Mohamed El-Tanani
- Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
| | - Gowhar A Naikoo
- Department of Mathematics and Sciences, College of Arts and Applied Sciences, Dhofar University, Salalah PC 211, Oman
| | - Nitin Charbe
- Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics (Lake Nona), University of Florida, Orlando, FL, USA
| | | | - Murtaza M Tambuwala
- Lincoln Medical School, University of Lincoln, Brayford Pool Campus, Lincoln LN6 7TS. United Kingdom
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13
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Dhaliwal J, Benchimol EI. The Incidence of IBD Among South Asian Children is Rising-But are the Phenotype and Outcomes Distinct? J Pediatr Gastroenterol Nutr 2023; 76:697-698. [PMID: 36917835 DOI: 10.1097/mpg.0000000000003767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Affiliation(s)
- Jasbir Dhaliwal
- From the Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
- the Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH
| | - Eric I Benchimol
- the SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada
- the Child Health Evaluative Sciences, SickKids Research institute, The Hospital for Sick Children, Toronto, ON, Canada
- the Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
- ICES, Toronto, ON, Canada
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14
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Greywoode R, Petralia F, Ullman TA, Frederic Colombel J, Ungaro RC. Racial Difference in Efficacy of Golimumab in Ulcerative Colitis. Inflamm Bowel Dis 2023; 29:843-849. [PMID: 35913121 PMCID: PMC10233400 DOI: 10.1093/ibd/izac161] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Observational studies have described racial differences in inflammatory bowel disease (IBD) genetics, clinical manifestations, and outcomes. Whether race impacts response to biologics in IBD is unclear. We conducted a post hoc analysis of phase 2 and 3 randomized clinical trials in ulcerative colitis to evaluate the effect of race on response to golimumab. METHODS We analyzed pooled individual-level data from induction and maintenance trials of golimumab through the Yale Open Data Access Project. The primary outcome was clinical response. Secondary outcomes were clinical remission and endoscopic healing. Multivariable logistic regression was performed comparing White vs racial minority groups (Asian, Black, or other race), adjusting for potential confounders. RESULTS There were 1006 participants in the induction (18% racial minority) and 783 participants in the maintenance (17% racial minority) trials. Compared with White participants, participants from racial minority groups had significantly lower clinical response (adjusted odds ratio [aOR], 0.43; 95% confidence interval [CI], 0.28-0.66), clinical remission (aOR, 0.41; 95% CI, 0.22-0.77), and endoscopic healing (aOR, 0.48; 95% CI, 0.31-0.74) at week 6. Participants from racial minority groups also had significantly lower clinical remission (aOR, 0.46; 95% CI, 0.28-0.74) and endoscopic healing (aOR, 0.63; 95% CI, 0.41-0.96) at week 30. There were no racial differences in placebo response rates. CONCLUSIONS Ulcerative colitis participants from racial minority groups were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared with White participants in induction and maintenance trials. Further studies are needed to understand the impact of race on therapeutic response in IBD.
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Affiliation(s)
- Ruby Greywoode
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Francesca Petralia
- Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Thomas A Ullman
- Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Jean Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ryan C Ungaro
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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15
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Shon WJ, Song JW, Oh SH, Lee KH, Seong H, You HJ, Seong JK, Shin DM. Gut taste receptor type 1 member 3 is an intrinsic regulator of Western diet-induced intestinal inflammation. BMC Med 2023; 21:165. [PMID: 37118698 PMCID: PMC10148556 DOI: 10.1186/s12916-023-02848-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 03/24/2023] [Indexed: 04/30/2023] Open
Abstract
BACKGROUND Long-term intake of a Western diet (WD), characterized by a high-fat content and sugary drinks, is hypothesized to contribute to the development of inflammatory bowel disease (IBD). Despite the identified clinical association, the molecular mechanisms by which dietary changes contribute to IBD development remain unknown. Therefore, we examined the influence of long-term intake of a WD on intestinal inflammation and the mechanisms by which WD intake affects IBD development. METHODS Mice fed normal diet or WD for 10 weeks, and bowel inflammation was evaluated through pathohistological and infiltrated inflammatory cell assessments. To understand the role of intestinal taste receptor type 1 member 3 (TAS1R3) in WD-induced intestinal inflammation, cultured enteroendocrine cells harboring TAS1R3, subjected to RNA interference or antagonist treatment, and Tas1r3-deficient mice were used. RNA-sequencing, flow cytometry, 16S metagenomic sequencing, and bioinformatics analyses were performed to examine the involved mechanisms. To demonstrate their clinical relevance, intestinal biopsies from patients with IBD and mice with dextran sulfate sodium-induced colitis were analyzed. RESULTS Our study revealed for the first time that intestinal TAS1R3 is a critical mediator of WD-induced intestinal inflammation. WD-fed mice showed marked TAS1R3 overexpression with hallmarks of serious bowel inflammation. Conversely, mice lacking TAS1R3 failed to exhibit inflammatory responses to WD. Mechanistically, intestinal transcriptome analysis revealed that Tas1r3 deficiency suppressed mTOR signaling, significantly increasing the expression of PPARγ (a major mucosal defense enhancer) and upregulating the expression of PPARγ target-gene (tight junction protein and antimicrobial peptide). The gut microbiota of Tas1r3-deficient mice showed expansion of butyrate-producing Clostridia. Moreover, an increased expression of host PPARγ-signaling pathway proteins was positively correlated with butyrate-producing microbes, suggesting that intestinal TAS1R3 regulates the relationship between host metabolism and gut microflora in response to dietary factors. In cultured intestinal cells, regulation of the TAS1R3-mTOR-PPARγ axis was critical for triggering an inflammatory response via proinflammatory cytokine production and secretion. Abnormal regulation of the axis was observed in patients with IBD. CONCLUSIONS Our findings suggest that the TAS1R3-mTOR-PPARγ axis in the gut links Western diet consumption with intestinal inflammation and is a potential therapeutic target for IBD.
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Affiliation(s)
- Woo-Jeong Shon
- Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-Gu, Seoul, 08826, Republic of Korea.
- Research Institute of Human Ecology, Seoul National University, Seoul, Republic of Korea.
| | - Jae Won Song
- Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-Gu, Seoul, 08826, Republic of Korea
| | - Seung Hoon Oh
- Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-Gu, Seoul, 08826, Republic of Korea
| | - Keon-Hee Lee
- Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-Gu, Seoul, 08826, Republic of Korea
| | - Hobin Seong
- Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-Gu, Seoul, 08826, Republic of Korea
| | - Hyun Ju You
- Bio-MAX/N-Bio, Seoul National University, Seoul, Republic of Korea
| | - Je Kyung Seong
- Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
- Korea Mouse Phenotyping Center, Seoul, Republic of Korea
| | - Dong-Mi Shin
- Department of Food and Nutrition, Seoul National University College of Human Ecology, Gwanak-Gu, Seoul, 08826, Republic of Korea
- Research Institute of Human Ecology, Seoul National University, Seoul, Republic of Korea
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16
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Wang R, Li Z, Liu S, Zhang D. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019. BMJ Open 2023; 13:e065186. [PMID: 36977543 PMCID: PMC10069527 DOI: 10.1136/bmjopen-2022-065186] [Citation(s) in RCA: 194] [Impact Index Per Article: 97.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/30/2023] Open
Abstract
OBJECTIVES We aimed to provide the most updated estimates on the global burden of inflammatory bowel disease (IBD) to improve management strategies. DESIGN We extracted data from the Global Burden of Disease (GBD) 2019 database to evaluate IBD burden with different measures in 204 countries and territories from 1990 to 2019. SETTING Studies from the GBD 2019 database generated by population-representative data sources identified through a literature review and research collaborations were included. PARTICIPANTS Patients with an IBD diagnosis. OUTCOMES Total numbers, age-standardised rates of prevalence, mortality and disability-adjusted life-years (DALYs), and their estimated annual percentage changes (EAPCs) were the main outcomes. RESULTS In 2019, there were approximately 4.9 million cases of IBD worldwide, with China and the USA having the highest number of cases (911 405 and 762 890 (66.9 and 245.3 cases per 100 000 people, respectively)). Between 1990 and 2019, the global age-standardised rates of prevalence, deaths and DALYs decreased (EAPCs=-0.66,-0.69 and -1.04, respectively). However, the age-standardised prevalence rate increased in 13 out of 21 GBD regions. A total of 147 out of 204 countries or territories experienced an increase in the age-standardised prevalence rate. From 1990 to 2019, IBD prevalent cases, deaths and DALYs were higher among females than among males. A higher Socio-demographic Index was associated with higher age-standardised prevalence rates. CONCLUSIONS IBD will continue to be a major public health burden due to increasing numbers of prevalent cases, deaths and DALYs. The epidemiological trends and disease burden of IBD have changed dramatically at the regional and national levels, so understanding these changes would be beneficial for policy makers to tackle IBD.
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Affiliation(s)
- Rui Wang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, China
| | - Zhaoqi Li
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, China
| | - Shaojun Liu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, China
| | - Decai Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, China
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17
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Wang R, Li Z, Liu S, Zhang D. Global, regional, and national burden of 10 digestive diseases in 204 countries and territories from 1990 to 2019. Front Public Health 2023; 11:1061453. [PMID: 37056655 PMCID: PMC10088561 DOI: 10.3389/fpubh.2023.1061453] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 03/06/2023] [Indexed: 03/30/2023] Open
Abstract
BackgroundDigestive diseases are very common worldwide and account for considerable health care use and expenditures. However, there are no global population-based estimates of the disease burden and temporal trend of digestive diseases.MethodsAnnual case numbers, age-standardized rates of prevalence, incidence, death, and disability-adjusted life-years (DALYs), and their estimated annual percentage changes (EAPCs) for digestive diseases between 1990 and 2019 were derived from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019. The association between digestive disease burden and the sociodemographic index (SDI) was investigated. We also calculated DALYs attributable to risk factors that had evidence of causation with digestive diseases.ResultsGlobally, in 2019, there were 88.99 million DALYs due to digestive diseases (3.51% of global DALYs). Digestive diseases were the 13th leading cause of DALYs globally in 2019. Global digestive disease DALYs were highest in the middle SDI quintile and in South Asia and were higher in males than females in 2019. Cirrhosis and other chronic liver diseases constituted the highest proportion of categorized digestive disease DALY burdens globally. From 1990 to 2019, the global age-standardized DALY rate of digestive diseases decreased from 1570.35 in 1990 to 1096.99 in 2019 per 1,00,000 population, with the EAPC being −1.32 (95% confidence interval [CI] −1.36 to −1.27). In 2019, the largest contributor to digestive disease DALYs at the global level, for both sexes, was alcohol use.ConclusionThe results of this systematic analysis suggest that the global burden of digestive diseases is substantial and varies markedly according to age, sex, SDI, and geographical region. These results provide comprehensive and comparable estimates that can potentially inform efforts toward digestive disease control worldwide.
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Affiliation(s)
- Rui Wang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Zhaoqi Li
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Shaojun Liu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
| | - Decai Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Non-resolving Inflammation and Cancer, Changsha, Hunan, China
- *Correspondence: Decai Zhang
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18
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Ohkusa T, Nishikawa Y, Sato N. Gastrointestinal disorders and intestinal bacteria: Advances in research and applications in therapy. Front Med (Lausanne) 2023; 9:935676. [PMID: 36825261 PMCID: PMC9941163 DOI: 10.3389/fmed.2022.935676] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 12/27/2022] [Indexed: 02/09/2023] Open
Abstract
Intestinal bacteria coexist with humans and play a role in suppressing the invasion of pathogens, producing short-chain fatty acids, producing vitamins, and controlling the immune system. Studies have been carried out on culturable bacterial species using bacterial culture methods for many years. However, as metagenomic analysis of bacterial genes has been developed since the 1990s, it has recently revealed that many bacteria in the intestine cannot be cultured and that approximately 1,000 species and 40 trillion bacteria are present in the gut microbiota. Furthermore, the composition of the microbiota is different in each disease state compared with the healthy state, and dysbiosis has received much attention as a cause of various diseases. Regarding gastrointestinal diseases, dysbiosis has been reported to be involved in inflammatory bowel disease, irritable bowel syndrome, and non-alcoholic steatohepatitis. Recent findings have also suggested that dysbiosis is involved in colon cancer, liver cancer, pancreatic cancer, esophageal cancer, and so on. This review focuses on the relationship between the gut microbiota and gastrointestinal/hepatobiliary diseases and also discusses new therapies targeting the gut microbiota.
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Affiliation(s)
| | - Yuriko Nishikawa
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Nobuhiro Sato
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
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19
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Chen Y, Zhang G, Yang Y, Zhang S, Jiang H, Tian K, Arenbaoligao, Chen D. The treatment of inflammatory bowel disease with monoclonal antibodies in Asia. Biomed Pharmacother 2023; 157:114081. [PMID: 36481399 DOI: 10.1016/j.biopha.2022.114081] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/27/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), are chronic, systemic autoimmune diseases. As the incidence of IBD rapidly increases in Asia, increasing attention has been paid to developing additional treatment strategies. Presently, the end point of therapy is achieving clinical and endoscopic remission through the blockade of inflammatory cascades. Recent studies have shown that monoclonal antibodies (mAbs) use for precise molecular targeting of inflammatory pathways has a promising effect on IBD, especially moderate-to-severe CD and UC. Since the 1997 report on the use of infliximab (a monoclonal antibody against tumor necrosis factor alpha [TNF-α]) in patients with CD, mAbs have expanded therapeutic options and have also complicated initial management options and subsequent treatment. This review comprehensively summarizes the clinical reports and studies related to the use of mAbs for the treatment of IBD in Asian countries and regions in recent years thus demonstrating the current status of mAbs use in Asia. In addition, the differences in the use of mAbs for the treatment of IBD between the Asia and the West are expounded. Ultimately, it is hoped that this review will provide new insights and a scientific basis for the clinical application of mAbs.
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Affiliation(s)
- Yu Chen
- Dalian Medical University, Dalian, China
| | | | | | | | - Haozheng Jiang
- Department of Joint and Sports Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Kang Tian
- Department of Joint and Sports Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
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20
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Burisch J. Editorial: trends in the epidemiology of inflammatory bowel disease in Korea. Aliment Pharmacol Ther 2022; 56:1207-1208. [PMID: 36071013 DOI: 10.1111/apt.17152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
- Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
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21
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Lim SZ, Chuah KH, Rajaram RB, Stanley K, Shahrani S, Chan WK, Ho SH, Hilmi IN, Goh KL, Mahadeva S. Epidemiological trends of gastrointestinal and liver diseases in Malaysia: A single-center observational study. J Gastroenterol Hepatol 2022; 37:1732-1740. [PMID: 35637160 DOI: 10.1111/jgh.15905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 05/11/2022] [Accepted: 05/25/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM The spectrum of gastrointestinal (GI) and liver diseases is recognized to have a geographical variation, which may be due to environmental or genetic differences. We aimed to explore this further in a specialist clinic serving a multi-ethnic Asian urban population. METHODS A retrospective analysis of outpatient data from this institution's electronic medical records was conducted between January and June 2019. Clinical diagnoses of GI and liver diseases and associated demographic information were collected. RESULTS Data from 3676 adult patients (median age 62 years, female 51.1%) were available for analysis. The frequency of luminal GI, liver and pancreato-biliary diseases were 34.2%, 63.2%, and 2.6%, respectively. Among luminal GI diseases, 38.6% were functional gastrointestinal disorders and 61.4% had an organic cause. A higher proportion of patients of Indian ethnicity were diagnosed with IBD compared with other ethnic groups (India 21.9%, Malay 16.5%, Chinese 12.2%, P = 0.001). Among liver diseases, the most common etiologies were HBV (44.4%) and NAFLD (39.3%). Cirrhosis and/or hepatocellular carcinoma were present in 18% of liver diseases, with NAFLD as the most frequent etiology. Among patients with NAFLD, a higher proportion of ethnic Malays and Indians were evident (Malay 53.8% vs Chinese 28.7% vs Indian 61.1%, P < 0.001). In contrast, a greater proportion of ethnic Chinese were diagnosed with HBV compared with other ethnic groups (Malay 30.9% vs Chinese 57.5% vs Indian 8.4%, P < 0.001). CONCLUSION The spectrum of GI and liver diseases has a peculiar epidemiology, particularly with reference to the ethnic predilection of certain diseases.
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Affiliation(s)
- Sze Zee Lim
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Kee Huat Chuah
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Ruveena Bhavani Rajaram
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Khoo Stanley
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shahreedhan Shahrani
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Wah Kheong Chan
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Shiaw Hooi Ho
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Ida Normiha Hilmi
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Khean Lee Goh
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Sanjiv Mahadeva
- Gastroenterology and Hepatology Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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22
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Abdulla M, Mohammed N. A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances. Biologics 2022; 16:129-140. [PMID: 36118798 PMCID: PMC9481278 DOI: 10.2147/btt.s380027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 08/27/2022] [Indexed: 11/24/2022]
Abstract
Inflammatory bowel diseases are considered immune disorders with a complex genetic architecture involving constantly changing endogenous and exogenous factors. The rapid evolution of genomic technologies and the emergence of newly discovered molecular actors are compelling the research community to reevaluate the knowledge and molecular processes. The human intestinal tract contains intestinal human microbiota consisting of commensal, pathogenic, and symbiotic strains leading to immune responses that can contribute and lead to both systemic and intestinal disorders including IBD. In this review, we attempted to highlight some updates of the new IBD features related to genomics, microbiota, new emerging therapies and some major established IBD risk factors.
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Affiliation(s)
- Maheeba Abdulla
- Internal Medicine Department, Ibn AlNafees Hospital, Arabian Gulf University, Manama, Bahrain
- Correspondence: Maheeba Abdulla, Consultant Gastroenterologist, Internal Medicine Department, Ibn AlNafees Hospital, Arabian Gulf University, Manama, Bahrain, Email
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23
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Park SH, Park SH. Personalized medicine in inflammatory bowel disease: Perspectives on Asia. J Gastroenterol Hepatol 2022; 37:1434-1445. [PMID: 35726657 DOI: 10.1111/jgh.15919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 06/10/2022] [Accepted: 06/18/2022] [Indexed: 12/09/2022]
Abstract
Inflammatory bowel diseases are chronic, relapsing inflammatory disorders of the gastrointestinal tract with variable disease courses and complications, which in some cases can result in significant morbidities and disabilities. Etiologies remain unclear due to complex interactions between genetic and environmental factors. Considering the heterogeneity of inflammatory bowel diseases, personalized approaches in diagnosing and managing affected patients would be beneficial in maximizing treatment efficacies and minimizing adverse events. Personalized medicine may also help to stratify patients with a high risk of progression and inflammatory bowel disease-related complications and identify sub-phenotypic mechanisms to facilitate drug discovery and the development of new treatments. In Asia, with a rapidly increasing incidence and prevalence of inflammatory bowel diseases, studies have shown that patients of Asian ethnicity differ from their Western counterparts in terms of genetic and clinical aspects of inflammatory bowel diseases. Therefore, personalized medicine may differ for patients of Asian ethnicity with inflammatory bowel diseases. We reviewed and summarized current evidence concerning personalized medicine for the diagnosis and management of patients with inflammatory bowel diseases and its possible role from an Asian perspective.
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Affiliation(s)
- Su Hyun Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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24
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Chatterjee K, Dutta AK, Goel A, Aaron R, Balakrishnan V, Thomas A, John A, Jaleel R, David D, Kurien RT, Chowdhury SD, Simon EG, Joseph AJ, Premkumar P, Pulimood AB. Common polymorphisms of protein tyrosine phosphate non-receptor type 2 gene are not associated with risk of Crohn’s disease in Indian. World J Gastrointest Pathophysiol 2022; 13:114-123. [PMID: 36161231 PMCID: PMC9350595 DOI: 10.4291/wjgp.v13.i4.114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/18/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Multiple genetic risk factors for Crohn’s disease (CD) have been identified. However, these observations are not consistent across different populations. The protein tyrosine phosphate non-receptor type 2 (PTPN2) gene plays a role in various aspects of host defense including epithelial barrier function, autophagy, and innate and adaptive immune response. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) have been associated with risk of CD in Western countries.
AIM To evaluate the association of PTPN2 gene polymorphisms with risk of CD in Indian population.
METHODS We conducted a prospective case-control study. Patients with CD were recruited, and their clinical and investigation details were noted. Controls were patients without organic gastrointestinal disease or other comorbid illnesses. Two common polymorphisms in the PTPN2 gene (rs2542151 and rs7234029) were assessed. DNA was extracted from peripheral blood samples of cases and controls and target DNA was amplified using specific sets of primers. The amplified fragments were digested with restriction enzymes and the presence of polymorphism was detected by restriction fragment length polymorphism. The frequency of alleles was determined. The frequencies of genotypes and alleles were compared between cases and controls to look for significant differences.
RESULTS A total of 108 patients with CD (mean age 37.5 ± 12.7 years, females 42.6%) and 100 controls (mean age 39.9 ± 13.5 years, females 37%) were recruited. For the single nucleotide polymorphism (SNP) rs7234029, the overall frequency of G variant genotype (AG or GG) was noted to be significantly lower in the cases compared to controls (35.2% vs 50%, P = 0.05). For the SNP rs2542151, the overall frequency of G variant genotype (GT or GG) was noted to be similar in cases compared to controls (43.6% vs 47%, P = 0.73). There were no significant differences in minor allele (G) frequency for both polymorphisms between the cases and controls. Both the SNPs had no significant association with age of onset of illness, gender, disease location, disease behaviour, perianal disease, or extraintestinal manifestations of CD.
CONCLUSION Unlike observation form the West, polymorphisms in the PTPN2 gene (rs7234029 and rs2542151) are not associated with an increased risk of developing CD in Indian patients.
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Affiliation(s)
- Kaushik Chatterjee
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Amit Kumar Dutta
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Ashish Goel
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Rekha Aaron
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Vijayalekshmi Balakrishnan
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Ajith Thomas
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Anoop John
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Rajeeb Jaleel
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Deepu David
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Reuben Thomas Kurien
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - SD Chowdhury
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
| | - Ebby George Simon
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - AJ Joseph
- Department of Gastroenterology, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Prasanna Premkumar
- Departments of Biostatistics, Christian Medical College, Vellore 632004, Tamil Nadu, India
| | - Anna B Pulimood
- Department of Gastrointestinal Sciences, Christian Medical College and Hospital, Vellore 632004, Tamil Nadu, India
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25
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Arkenbosch JHC, Mak JWY, Ho JCL, Beelen EMJ, Erler NS, Hoentjen F, Bodelier AGL, Dijkstra G, Romberg-Camps M, de Boer NKH, Stassen LPS, van der Meulen AE, West R, van Ruler O, van der Woude CJ, Ng SC, de Vries AC. Indications, Postoperative Management, and Long-term Prognosis of Crohn's Disease After Ileocecal Resection: A Multicenter Study Comparing the East and West. Inflamm Bowel Dis 2022; 28:S16-S24. [PMID: 34969091 DOI: 10.1093/ibd/izab316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The Crohn's disease (CD) phenotype differs between Asian and Western countries and may affect disease management, including decisions on surgery. This study aimed to compare the indications, postoperative management, and long-term prognosis after ileocecal resection (ICR) in Hong Kong (HK) and the Netherlands (NL). METHODS CD patients with primary ICR between 2000 and 2019 were included. The endpoints were endoscopic (Rutgeerts score ≥i2b and/or radiologic recurrence), clinical (start or switch of inflammatory bowel disease medication), and surgical recurrences. Cumulative incidences of recurrence were estimated with a Bayesian multivariable proportional hazards model. RESULTS Eighty HK and 822 NL patients were included. The most common indication for ICR was penetrating disease (HK: 32.5%, NL: 22.5%) in HK vs stricturing disease (HK: 32.5%, NL: 48.8%) in the NL (P < .001). Postoperative prophylaxis was prescribed to 65 (81.3%) HK patients (28 [35.0%] aminosalicylates [5-aminosalicylic acid]; 30 [37.5%] immunomodulators; 0 biologicals) vs 388 (47.1%) NL patients (67 [8.2%] 5-aminosalicylic acid; 187 [22.8%] immunomodulators; 69 [8.4%] biologicals; 50 [6.1%] combination therapy) (P < .001). Endoscopic or radiologic evaluation within 18 months was performed in 36.3% HK vs 64.1% NL (P < .001) patients. No differences between both populations were observed for endoscopic (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.24-1.21), clinical (HR, 0.91; 95% CI, 0.62-1.32), or surgical (HR, 0.61; 95% CI, 0.31-1.13) recurrence risks. CONCLUSION The main indication for ICR in CD patients is penetrating disease in HK patients and stricturing disease in NL patients. Although considerable pre- and postoperative management differences were observed between the two geographical areas, the long-term prognosis after ICR is similar.
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Affiliation(s)
- Jeanine H C Arkenbosch
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Joyce W Y Mak
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Jacky C L Ho
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Evelien M J Beelen
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Nicole S Erler
- Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands.,Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Frank Hoentjen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.,Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | | | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, the Netherlands
| | - Mariëlle Romberg-Camps
- Department of Gastroenterology and Hepatology, Zuyderland Medical Center, Sittard-Geleen, the Netherlands
| | - Nanne K H de Boer
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, AGEM Research Institute, Amsterdam, the Netherlands
| | - Laurents P S Stassen
- Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Andrea E van der Meulen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
| | - Rachel West
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis and Vlietland, Rotterdam, the Netherlands
| | - Oddeke van Ruler
- Department of Surgery, IJsselland Hospital, Capelle aan den IJssel, the Netherlands.,Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
| | | | - Siew C Ng
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
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26
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Foerster EG, Mukherjee T, Cabral-Fernandes L, Rocha JD, Girardin SE, Philpott DJ. How autophagy controls the intestinal epithelial barrier. Autophagy 2022; 18:86-103. [PMID: 33906557 PMCID: PMC8865220 DOI: 10.1080/15548627.2021.1909406] [Citation(s) in RCA: 192] [Impact Index Per Article: 64.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 03/15/2021] [Accepted: 03/23/2021] [Indexed: 02/07/2023] Open
Abstract
Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress through tight junction regulation and protection from cell death. Furthermore, a clear role has emerged for autophagy not only in secretory cells but also in intestinal stem cells, where it affects their metabolism, as well as their proliferative and regenerative capacity. Here, we review the physiological role of autophagy in the context of intestinal epithelial maintenance and how genetic mutations affecting autophagy contribute to the development of intestinal disease.Abbreviations: AKT1S1: AKT1 substrate 1; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; APC: APC regulator of WNT signaling pathway; ATF6: activating transcription factor 6; ATG: autophagy related; atg16l1[ΔIEC] mice: mice with a specific deletion of Atg16l1 in intestinal epithelial cells; ATP: adenosine triphosphate; BECN1: beclin 1; bsk/Jnk: basket; CADPR: cyclic ADP ribose; CALCOCO2: calcium binding and coiled-coil domain 2; CASP3: caspase 3; CD: Crohn disease; CDH1/E-cadherin: cadherin 1; CF: cystic fibrosis; CFTR: CF transmembrane conductance regulator; CGAS: cyclic GMP-AMP synthase; CLDN2: claudin 2; CoPEC: colibactin-producing E. coli; CRC: colorectal cancer; CYP1A1: cytochrome P450 family 1 subfamily A member 1; DC: dendritic cell; DDIT3: DNA damage inducible transcript 3; DEPTOR: DEP domain containing MTOR interacting protein; DSS: dextran sulfate sodium; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2AK4/GCN2: eukaryotic translation initiation factor 2 alpha kinase 4; ER: endoplasmic reticulum; ERN1: endoplasmic reticulum to nucleus signaling 1; GABARAP: GABA type A receptor-associated protein; HMGB1: high mobility group box 1; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; IBD: inflammatory bowel disease; IEC: intestinal epithelial cell; IFN: interferon; IFNG/IFNγ:interferon gamma; IL: interleukin; IRGM: immunity related GTPase M; ISC: intestinal stem cell; LGR5: leucine rich repeat containing G protein-coupled receptor 5; LRRK2: leucine rich repeat kinase 2; MAP1LC3A/LC3: microtubule associated protein 1 light chain 3 alpha; MAPK/JNK: mitogen-activated protein kinase; MAPK14/p38 MAPK: mitogen-activated protein kinase 14; MAPKAP1: MAPK associated protein 1; MAVS: mitochondrial antiviral signaling protein; miRNA: microRNA; MLKL: mixed lineage kinase domain like pseudokinase; MLST8: MTOR associated protein, LST8 homolog; MNV: murine norovirus; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; NLRP: NLR family pyrin domain containing; NOD: nucleotide binding oligomerization domain containing; NRBF2: nuclear receptor binding factor 2; OPTN: optineurin; OXPHOS: oxidative phosphorylation; P: phosphorylation; Patj: PATJ crumbs cell polarity complex component; PE: phosphatidyl-ethanolamine; PI3K: phosphoinositide 3-kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; PPARG: peroxisome proliferator activated receptor gamma; PRR5: proline rich 5; PRR5L: proline rich 5 like; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RER: rough endoplasmic reticulum; RHEB: Ras homolog, MTORC1 binding; RICTOR: RPTOR independent companion of MTOR complex 2; RIPK1: receptor interacting serine/threonine kinase 1; ROS: reactive oxygen species; RPTOR: regulatory associated protein of MTOR complex 1; RPS6KB1: ribosomal protein S6 kinase B1; SH3GLB1: SH3 domain containing GRB2 like, endophilin B1; SNP: single-nucleotide polymorphism; SQSTM1: sequestosome 1; STAT3: signal transducer and activator of transcription 3; STING1: stimulator of interferon response cGAMP interactor 1; TA: transit-amplifying; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; TGM2: transglutaminase 2; TJ: tight junction; TJP1/ZO1: tight junction protein 1; TNBS: 2,4,6-trinitrobenzene sulfonic acid; TNF/TNFα: tumor necrosis factor; Tor: target of rapamycin; TRAF: TNF receptor associated factor; TRIM11: tripartite motif containing 11; TRP53: transformation related protein 53; TSC: TSC complex subunit; Ub: ubiquitin; UC: ulcerative colitis; ULK1: unc-51 like autophagy activating kinase 1; USO1/p115: USO1 vesicle transport factor; UVRAG: UV radiation resistance associated; WIPI: WD repeat domain, phosphoinositide interacting; WNT: WNT family member; XBP1: X-box binding protein 1; ZFYVE1/DFCP1: zinc finger FYVE-type containing 1.
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Affiliation(s)
| | - Tapas Mukherjee
- Department of Immunology, University of Toronto, Toronto, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | | | | | - Stephen E. Girardin
- Department of Immunology, University of Toronto, Toronto, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Dana J. Philpott
- Department of Immunology, University of Toronto, Toronto, Canada
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27
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Chin YH, Ng CH, Lin SY, Jain SR, Kong G, Koh JWH, Tan DJH, Ong DEH, Muthiah MD, Chong CS, Foo FJ, Leong R, Chan WPW. Systematic review with meta-analysis: The prevalence, risk factors and outcomes of upper gastrointestinal tract Crohn's disease. Dig Liver Dis 2021; 53:1548-1558. [PMID: 34412995 DOI: 10.1016/j.dld.2021.07.037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/28/2021] [Accepted: 07/21/2021] [Indexed: 12/11/2022]
Abstract
AIMS Upper gastrointestinal Crohn's disease (UGI-CD) is an important subclassification of Crohn's Disease (CD). We performed a systematic review and meta-analysis to evaluate the prevalence, risk factors, and clinical outcomes associated with UGI-CD. METHODS We searched Embase and Medline for articles reporting the clinical information of UGI-CD in CD patients, through 27 October 2020. Disease location and phenotype were coded according to the Montreal classification, and results were pooled with random effects by DerSimonian and Laird model. RESULTS 26 articles were included. The prevalence of UGI-CD was 13%. UGI-CD was most commonly found in the stomach (56%) and was associated with concurrent ileocolonic involvement (54%). Non-stricturing, non-penetrating UGI-CD was the most common behavioral phenotype (61%). L4-jejunal disease was associated with the highest rates of surgery. Region of origin did not significantly influence the location and phenotype of UGI-CD. Young, male patients presenting with erythema nodosum, aphthous ulcers and stricturing-phenotype are more likely to have UGI-CD, which in turn is linked to increased risk of hospitalization and surgery. CONCLUSION UGI-CD is present in 13% of patients with CD, and patients with L4-jejunal disease are more likely to require surgery. Further studies examining the effect of ethnicity and region on UGI-CD are needed.
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Affiliation(s)
- Yip Han Chin
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Snow Yunni Lin
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Sneha Rajiv Jain
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Gwyneth Kong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | | | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - David Eng Hui Ong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital
| | - Mark Dhinesh Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital
| | - Choon Seng Chong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore; Division of Colorectal Surgery, Department of Surgery, University Surgical Cluster, National University Hospital, Singapore, Singapore
| | | | - Rupert Leong
- The University of Sydney, Sydney, New South Wales, Australia; Concord Repatriation General Hospital, Sydney, New South Wales, Australia
| | - Webber Pak Wo Chan
- Department of Gastroenterology, Singapore General Hospital, Singapore, 20 College Road, Academia level 3, Singapore 169856.
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28
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Dhaliwal J, Tuna M, Shah BR, Murthy S, Herrett E, Griffiths AM, Benchimol EI. Incidence of Inflammatory Bowel Disease in South Asian and Chinese People: A Population-Based Cohort Study from Ontario, Canada. Clin Epidemiol 2021; 13:1109-1118. [PMID: 34876857 PMCID: PMC8643128 DOI: 10.2147/clep.s336517] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/12/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is now a global disease with incidence increasing throughout Asia. AIM To determine the incidence of IBD among South Asians and Chinese people residing in Ontario, Canada's most populous province. METHODS All incident cases of IBD in children (1994-2015) and adults (1999-2015) were identified from population-based health administrative data. We classified South Asian and Chinese ethnicity using immigration records and surnames. We determined standardized incidence of IBD and adjusted incidence rate ratio (aIRR) in South Asians and Chinese compared to the general population. RESULTS Among 16,230,638 people living in Ontario, standardized incidence of IBD per 100,000 person-years was 24.7 (95% CI 24.4-25.0), compared with 14.6 (95% CI 13.7-15.5) in 982,472 South Asians and with 5.4 (95% CI 4.8-5.9) in 764,397 Chinese. The risk of IBD in South Asians was comparable to the general population after adjusting for immigrant status and confounders (aIRR 1.03, 95% CI 0.96-1.10). South Asians had a lower risk of Crohn's disease (CD) (aIRR 0.66, 95% CI 0.60-0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47, 95% CI 1.34-1.61). Chinese people had much lower rates of IBD (aIRR 0.24, 95% CI 0.20-0.28), CD (aIRR 0.21, 95% CI 0.17-0.26), and UC (aIRR 0.28, 95% CI 0.23-0.25). CONCLUSION Canadians of South Asian ethnicity had a similarly high risk of developing IBD compared to other Canadians, and a higher risk of developing UC, a finding distinct from the Chinese population. Our findings indicate the importance of genetic and environmental risk factors in people of Asian origin who live in the Western world.
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Affiliation(s)
- Jasbir Dhaliwal
- ICES, Toronto, ON, Canada
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Paediatrics, University of Toronto, Toronto, ON, Canada
- London School of Hygiene and Tropical Medicine, London, UK
- Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA
| | | | - Baiju R Shah
- ICES, Toronto, ON, Canada
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
| | - Sanjay Murthy
- ICES, Toronto, ON, Canada
- The Ottawa Hospital IBD Centre, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Emily Herrett
- London School of Hygiene and Tropical Medicine, London, UK
| | - Anne M Griffiths
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Paediatrics, University of Toronto, Toronto, ON, Canada
| | - Eric I Benchimol
- ICES, Toronto, ON, Canada
- SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Paediatrics, University of Toronto, Toronto, ON, Canada
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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Riansuwan W, Limsrivilai J. Current status of IBD and surgery of Crohn's disease in Thailand. Ann Gastroenterol Surg 2021; 5:597-603. [PMID: 34585044 PMCID: PMC8452468 DOI: 10.1002/ags3.12470] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/11/2021] [Accepted: 04/21/2021] [Indexed: 12/24/2022] Open
Abstract
Inflammatory bowel disease (IBD) consists of two diseases: ulcerative colitis (UC) and Crohn's disease (CD). The incidence of IBD is much higher in Western countries compared to Asian countries, especially in Thailand. The incidence of UC in Thailand is quite low and seems less aggressive than in Western countries. Over the past two decades, the evolution of UC management in Thailand has led to a reduction in hospitalization and colectomy rate. Regarding CD, the majority of patients have an inflammatory phenotype at diagnosis. Diagnosis of CD remains challenging in Thailand as the time from onset of symptoms to diagnosis is quite delayed, possibly due to unawareness and difficulty in the differential diagnosis between CD and other infectious entero-colitis such as intestinal tuberculosis. With a significant trend to early initiation of immunomodulators and biologics, the cumulative rate of surgery after diagnosis has been improved. To improve the outcomes of CD treatment in Thailand, physicians need more awareness to recognize the disease, which results in early diagnosis, prevention of long-term complications, and reduction in the rate of surgery.
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Affiliation(s)
- Woramin Riansuwan
- Colorectal Surgery UnitDivision of General SurgeryDepartment of SurgeryFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
| | - Julajak Limsrivilai
- Division of GastroenterologyDepartment of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkokThailand
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30
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Dhaliwal J, Carroll MW, deBruyn JC, Ricciuto A, Benchimol EI, Lawrence S, Sherlock M, El-Matary W, Brill H, Church P, Wine E, Carman N, Muise A, Huynh H, Mack DR, Walters TD, Griffiths AM, Jacobson K. The Phenotypic Spectrum of New-onset IBD in Canadian Children of South Asian Ethnicity: A Prospective Multi-Centre Comparative Study. J Crohns Colitis 2021; 16:216-223. [PMID: 34379117 PMCID: PMC8864632 DOI: 10.1093/ecco-jcc/jjab143] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. METHODS Patients aged <17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores. RESULTS Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2-14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p <0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity. CONCLUSIONS The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.
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Affiliation(s)
- J Dhaliwal
- SickKids Hospital, University of Toronto, Toronto, ON, Canada,Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
| | - M W Carroll
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | - J C deBruyn
- Alberta Children’s Hospital, University of Calgary, Calgary, AB, Canada
| | - A Ricciuto
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - E I Benchimol
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - S Lawrence
- British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada
| | - M Sherlock
- McMaster Children’s Hospital, McMaster University, Hamilton, ON, Canada
| | - W El-Matary
- Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - H Brill
- McMaster Children’s Hospital, McMaster University, Hamilton, ON, Canada,William Osler Health System, University of Toronto, Toronto, ON, Canada
| | - P Church
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - E Wine
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | - N Carman
- Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada
| | - A Muise
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - H Huynh
- Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
| | - D R Mack
- Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada
| | - T D Walters
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - A M Griffiths
- SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - K Jacobson
- British Columbia Children’s Hospital, University of British Columbia, Vancouver, BC, Canada,Corresponding author: Dr Kevan Jacobson, MBBCh, FRCPC, FCP, AGAF, CAGF, British Columbia’s Children’s Hospital and Child and Family Research Institute, University of British Columbia, 4480 Oak Street, Room K4-184, Vancouver, BC V6H 3V4, Canada. Tel.: 604-875-2332 ext 1;
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31
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Abdel-Wahab N, Diab A, Yu RK, Futreal A, Criswell LA, Tayar JH, Dadu R, Shannon V, Shete SS, Suarez-Almazor ME. Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors. Cancer Immunol Immunother 2021; 70:1939-1949. [PMID: 33409738 PMCID: PMC10992432 DOI: 10.1007/s00262-020-02797-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 11/08/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) can cause profound immune-related adverse events (irAEs). The host genetic background is likely to play a role in irAE susceptibility because the presentation of toxicity varies among patients and many do not develop irAEs despite continued ICI use. We sought to identify potential genetic markers conferring risk for irAEs. METHODS We conducted a pilot exploratory study in 89 melanoma patients who received ICIs (44 with irAEs, and 45 without irAEs after at least 1 year from starting treatment). Genotyping was performed using the Infinium Multi-Ethnic Global-8 v1.0 Bead Chip. The genotype data were extracted using PLINK (v1.90b3.34) and processed for quality control. Population structure-based clustering was carried out using IBS matrix, pairwise population concordance test (p < 1 × 10-3), and phenotype distribution for all study participants, resulting in seven population structure-based clusters. In the analytical stage, 599,931 variants in autosomal chromosomes were included for the association study. The association test was performed using an additive genetic model with exact logistic regression, adjusted for age, sex, and population cluster. RESULTS A total of 30 variants or single-nucleotide polymorphisms with p < 1 × 10-4 were identified; 12 were associated with an increased risk of irAEs, and the remaining 18 were associated with a decreased risk. Overall, nine of the identified single-nucleotide polymorphisms mapped to eight unique genes that have been associated with autoimmunity or inflammatory diseases. CONCLUSION Several genetic variants associated with irAEs were identified. Additional larger studies are needed to validate these findings and establish their potential functional relevance.
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Affiliation(s)
- Noha Abdel-Wahab
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Adi Diab
- Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Robert K Yu
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Andrew Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Lindsey A Criswell
- Russell/Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
| | - Jean H Tayar
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ramona Dadu
- Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Vickie Shannon
- Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sanjay S Shete
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Maria E Suarez-Almazor
- Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Cai C, Zhu S, Tong J, Wang T, Feng Q, Qiao Y, Shen J. Relating the transcriptome and microbiome by paired terminal ileal Crohn disease. iScience 2021; 24:102516. [PMID: 34113837 PMCID: PMC8170125 DOI: 10.1016/j.isci.2021.102516] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 03/28/2021] [Accepted: 05/03/2021] [Indexed: 12/16/2022] Open
Abstract
Management of terminal ileal Crohn disease (CD) is difficult due to fibrotic prognosis and failure to achieve mucosal healing. A limited number of synchronous analyses have been conducted on the transcriptome and microbiome in unpaired terminal ileum tissues. Therefore, our study focused on the transcriptome and mucosal microbiome in terminal ileal tissues of patients with CD with the aim of determining the role of cross-talk between the microbiome and transcriptome in the pathogenesis of terminal ileal CD. Mucosa-attached microbial communities were significantly associated with segmental inflammation status. Interaction-related transcription factors (TFs) are the panel nodes for cross-talk between the gene patterns and microbiome for terminal ileal CD. The transcriptome and microbiome in terminal ileal CD can be differently related to the local inflammatory status, and specific differentially expressed genes may be targeted for mucosal healing. TFs connect gene patterns with the microbiome by reflecting environmental stimuli and signals from microbiota.
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Affiliation(s)
- Chenwen Cai
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Avenue, Shanghai 200127, China
- Department of Gastroenterology, Huashan Hospital North, Fudan University, No.108 LuXiang Road, Shanghai 201907, China
| | - Sibo Zhu
- MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200438, China
| | - Jinlu Tong
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Avenue, Shanghai 200127, China
| | - Tianrong Wang
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Avenue, Shanghai 200127, China
| | - Qi Feng
- Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pu Jian Road, Shanghai 200127, China
| | - Yuqi Qiao
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Avenue, Shanghai 200127, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Avenue, Shanghai 200127, China
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Abstract
Inflammatory bowel disease (IBD) in recent times is causing a significant healthcare burden as both ulcerative colitis and Crohn's disease (CD) require lifelong therapy and constant monitoring. The current review highlights the concerns in a country like India with special reference to the changing trends of IBD, risk attribution and the financial issues. Indian immigrants behave like residential Indians, whereas their children show IBD prevalence similar to the West, highlighting the role of environmental triggers. However, the environmental and genetic factors in Indians with IBD are not well understood. Men appear to be more frequently affected than women in India. The disease severity is milder in the patients, both males and females, but the risk for colorectal cancer (CRC) is similar to the West. The incidence of paediatric IBD is on the rise. The major burden of IBD in the Indian subcontinent at present is in children, adolescents and teens. Cost towards the management of complications, non-adherence to treatment, differentiating tuberculosis from CD and finally screening for CRC in patients with IBD are the points to ponder in the Indian scenario.
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Affiliation(s)
- Mayank Jain
- Department of Medical Gastroenterology, Gleneagles Global Health City, Chennai, India
| | - Jayanthi Venkataraman
- Department of Medical Gastroenterology, Gleneagles Global Health City, Chennai, India
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34
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Pinter M, Scheiner B, Peck-Radosavljevic M. Immunotherapy for advanced hepatocellular carcinoma: a focus on special subgroups. Gut 2021; 70:204-214. [PMID: 32747413 PMCID: PMC7788203 DOI: 10.1136/gutjnl-2020-321702] [Citation(s) in RCA: 166] [Impact Index Per Article: 41.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 05/27/2020] [Accepted: 06/13/2020] [Indexed: 02/06/2023]
Abstract
Following the success of immune checkpoint blockers (ICBs) in different cancer types, a large number of studies are currently investigating ICBs in patients with hepatocellular carcinoma (HCC), alone or in combination with other treatments. Both nivolumab and pembrolizumab, as well as the combination of nivolumab plus ipilimumab have been granted accelerated approval by the United States Food and Drug Administration for sorafenib-pretreated patients. While nivolumab and pembrolizumab both failed to meet their primary endpoints in phase III trials, the combination of atezolizumab plus bevacizumab eventually improved overall and progression-free survival compared with sorafenib in a front-line phase III trial, and thus, will become the new standard of care in this setting. Despite this breakthrough, there are patient populations with certain underlying conditions that may not be ideal candidates for this new treatment either due to safety concerns or potential lack of efficacy. In this review, we discuss the safety of ICBs in patients with pre-existing autoimmune disease, IBD or a history of solid organ transplantation. Moreover, we summarise emerging preclinical and clinical data suggesting that ICBs may be less efficacious in patients with underlying non-alcoholic steatohepatitis or HCCs with activated Wnt/β-catenin signalling.
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Affiliation(s)
- Matthias Pinter
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria .,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria,Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria
| | - Markus Peck-Radosavljevic
- Department of Internal Medicine and Gastroenterology (IMuG), Hepatology, Endocrinology, Rheumatology and Nephrology including Centralized Emergency Department (ZAE), Klinikum Klagenfurt am Worthersee, Klagenfurt, Kärnten, Austria
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35
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Banerjee R, Chuah SW, Hilmi IN, Wu DC, Yang SK, Demuth D, Lindner D, Adsul S. Efficacy and safety of vedolizumab in Crohn's disease in patients from Asian countries in the GEMINI 2 study. Intest Res 2020; 19:83-94. [PMID: 33378612 PMCID: PMC7873405 DOI: 10.5217/ir.2019.09160] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 05/08/2020] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND/AIMS The efficacy and safety of vedolizumab in moderate-to-severely active Crohn's disease (CD) were demonstrated in the GEMINI 2 study (NCT00783692). This post-hoc exploratory analysis aimed to assess the efficacy and safety of vedolizumab in the subgroup of patients from Asian countries. METHODS During the induction phase (doses at day 1, 15), clinical remission, enhanced clinical response, and change in C-reactive protein at 6 weeks; during the maintenance phase, clinical remission, enhanced clinical response, glucocorticoid-free remission and durable clinical remission at 52 weeks, were the efficacy outcomes of interest. Efficacy and safety of vedolizumab compared to placebo were assessed in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) using descriptive analyses. RESULTS During the induction phase, in Asian countries (n = 51), 14.7% of the vedolizumab-treated patients achieved clinical remission at week 6 compared to none with placebo (difference, 14.7%; 95% confidence interval, 15.8%-43.5%). In non-Asian countries (n = 317), the remission rate at week 6 with vedolizumab was 14.5%. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks and placebo were 41.7%, 36.4%, and 0%, respectively; while enhanced clinical response rates were 41.7%, 63.6%, and 42.9%, respectively. During induction, 39.7% of patients with vedolizumab experienced an adverse event compared to 58.8% of patients with placebo, and vedolizumab was generally well-tolerated. CONCLUSIONS This post-hoc analysis demonstrates the treatment effect and safety of vedolizumab in moderateto-severely active CD in patients from Asian countries.
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Affiliation(s)
- Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | | | | | - Deng-Chyang Wu
- Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Suk-Kyun Yang
- University of Ulsan College of Medicine, Seoul, Korea
| | - Dirk Demuth
- Takeda Pharmaceutical International AG, Singapore
| | - Dirk Lindner
- Takeda Pharmaceutical International AG, Zurich, Switzerland
| | - Shashi Adsul
- Takeda Pharmaceutical International AG, Zurich, Switzerland
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36
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Abstract
Immune checkpoint inhibitors (ICIs) such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors are widely used for the treatment of multiple cancers. Seven of these agents are currently FDA approved in the US as first or second line options for solid tumors and hematologic malignancies. These agents work by downregulating pathways that suppress T-cell activation and thereby mounting an immune response to the tumor. In general, ICI are well tolerated with only mild to moderate toxicity. However, in some patients severe immune-related adverse events (irAEs) that mimic the presentation of autoimmune diseases (AID) may occur. It is believed that irAEs occur due to disruption of immunologic self-tolerance, a mechanism that also seems to explain AID. Patients with pre-existing AID are usually excluded from prospective clinical trials due to concerns for flares of the underline AID. There is limited retrospective evidence supporting the use of ICI in patients with some pre-existing AID. These patients have an increased risk of malignancy and there is an unmet need to study ICIs in this population. This manuscript intends to review the current available evidence for the safety and activity of ICIs in patients with pre-existing AID. We summarize the reported use of ICI in patients with pre-existing AID according to the primary tumor site and type of ICI used.
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Affiliation(s)
- Sagar Rakshit
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
| | - Julian R Molina
- Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
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Abd El Aziz MA, Facciorusso A, Nayfeh T, Saadi S, Elnaggar M, Cotsoglou C, Sacco R. Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma. Vaccines (Basel) 2020; 8:vaccines8040616. [PMID: 33086471 PMCID: PMC7712941 DOI: 10.3390/vaccines8040616] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/06/2020] [Accepted: 10/14/2020] [Indexed: 12/13/2022] Open
Abstract
Despite the advances in screening protocols and treatment options, hepatocellular carcinoma (HCC) is still considered to be the most lethal malignancy in patients with liver cirrhosis. Moreover, the survival outcomes after failure of first-line therapy for unresectable HCC is still poor with limited therapeutic options. One of these options is immune checkpoint inhibitors. The aim of this study is to comprehensively review the efficacy and safety of immune checkpoint inhibitors for patients with HCC.
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Affiliation(s)
| | - Antonio Facciorusso
- Gastroenterology Unit, Department of Medical Sciences, Ospedali Riuniti di Foggia, 71122 Foggia, Italy;
| | - Tarek Nayfeh
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA; (T.N.); (S.S.)
| | - Samer Saadi
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN 55905, USA; (T.N.); (S.S.)
| | - Mohamed Elnaggar
- Department of Internal Medicine, Reno School of Medicine, University of Nevada, Las Vegas, NV 1155, USA;
| | | | - Rodolfo Sacco
- Gastroenterology Unit, Department of Medical Sciences, Ospedali Riuniti di Foggia, 71122 Foggia, Italy;
- Gastroenterology Unit, Department of Medical Sciences, Ospedali Riuniti di Foggia, Viale Pinto, 1, 71100 Foggia, Italy
- Correspondence:
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Chen B, Gao X, Zhong J, Ren J, Zhu X, Liu Z, Wu K, Kalabic J, Yu Z, Huang B, Kwatra N, Doan T, Robinson AM, Chen MH. Efficacy and safety of adalimumab in Chinese patients with moderately to severely active Crohn's disease: results from a randomized trial. Therap Adv Gastroenterol 2020; 13:1756284820938960. [PMID: 32733600 PMCID: PMC7370564 DOI: 10.1177/1756284820938960] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Accepted: 03/06/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Efficacy of adalimumab in Crohn's disease (CD) has not been shown in China. The aim of this study was to evaluate the efficacy and safety of adalimumab in Chinese patients with CD. METHODS This 26-week, multicenter, phase III study evaluated patients with moderately to severely active CD and elevated high-sensitivity C-reactive protein (⩾3 mg/l) who were naïve to anti-tumor necrosis factor therapy. Patients were randomized to double-blind adalimumab 160/80 mg at weeks 0/2 and 40 mg at weeks 4/6 or placebo at weeks 0/2 followed by blinded adalimumab 160/80 mg at weeks 4/6. At week 8, all patients received open-label 40 mg adalimumab every other week through week 26. The primary endpoint was clinical remission [CD activity index (CDAI) <150] at week 4. Clinical remission at week 26 was assessed in week-8 responders (decrease in CDAI ⩾70 points at week 8 from baseline) and compared with a clinically meaningful threshold of 30%. Adverse events (AEs) were recorded throughout the study. RESULTS At baseline, 205 patients were enrolled, with mean [standard deviation (SD)] age of 32.9 (9.9) years and CD duration of 2.7 (3.0) years. At week 4, 38/102 patients (37%) receiving adalimumab and 7/103 (7%) receiving placebo (p < 0.001) achieved clinical remission. Among week-8 responders, 93/144 (65%) achieved clinical remission at week 26 (p < 0.001). No unexpected AEs and no malignancies, active tuberculosis, or deaths were reported. CONCLUSIONS Adalimumab induced and maintained remission in Chinese patients with CD. Safety results were consistent with the known safety profile of adalimumab. CLINICALTRIALSGOV IDENTIFIER NCT02499783.
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Affiliation(s)
- Baili Chen
- The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiang Gao
- The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jie Zhong
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jianlin Ren
- Zhongshan Hospital Xiamen University, Xiamen, China
| | - Xuan Zhu
- The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhanju Liu
- Shanghai Tenth People’s Hospital, Shanghai, China
| | - Kaichun Wu
- The First Affiliated Hospital of Fourth Military Medical University, Xi’an, China
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Imawana RA, Smith DR, Goodson ML. The relationship between inflammatory bowel disease and Helicobacter pylori across East Asian, European and Mediterranean countries: a meta-analysis. Ann Gastroenterol 2020; 33:485-494. [PMID: 32879595 PMCID: PMC7406810 DOI: 10.20524/aog.2020.0507] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 05/06/2020] [Indexed: 12/12/2022] Open
Abstract
Background The current literature suggests a protective benefit of Helicobacter pylori (H. pylori) infection against inflammatory bowel disease (IBD). Here we assessed whether this effect varied by IBD subtype—Crohn’s disease (CD) or ulcerative colitis (UC)—and geographic region: East Asia, Europe (non-Mediterranean) or Mediterranean region. Methods A database search was performed up to July 2019 inclusive for all studies that compared H. pylori infection in IBD patients vs. non-IBD controls. The relative risk (RR) was used to quantify the association between IBD and H. pylori, and the effects were combined across studies using a mixed-effects meta-regression model, which included IBD subtype and geographic region as categorical moderator variables. Results Our meta-regression model exhibited moderate heterogeneity (I2=48.74%). Pooled RR depended on both region (P=0.02) and subtype (P<0.001). Pooled RRs were <1 for all subtype and region combinations, indicative of a protective effect of H. pylori against IBD. The pooled RR was 28% (9%, 50%; P=0.001) greater for UC vs. CD and 43% (4%, 96%; P=0.02) greater for Mediterranean countries vs. East Asia. The pooled RR was 18% (-13%, 60%; P=0.48) greater for Europe vs. East Asia and 21% (-13%, 68%; P=0.42) greater for Mediterranean vs. Europe, though these differences were not statistically significant. Conclusions The protective effect of H. pylori on IBD varied by both subtype (more protection against CD vs. UC) and region (East Asia more protected than Mediterranean regions). Variation due to these effects could provide insight into IBD etiology.
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Affiliation(s)
| | - Daniel Robert Smith
- Medical Research Department, Faculty of Medical Sciences, Newcastle University Medicine Malaysia
| | - Michaela Louise Goodson
- Medical Research Department, Faculty of Medical Sciences, Newcastle University Medicine Malaysia
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UK Patients of Bangladeshi Descent with Crohn's Disease Respond Less Well to TNF Antagonists Than Caucasian Patients. Dig Dis Sci 2020; 65:1790-1799. [PMID: 31655907 DOI: 10.1007/s10620-019-05907-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Accepted: 10/15/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease are currently managed with the assumption that trial data are applicable to all ethnic groups. Previous studies demonstrate differences in disease severity and phenotype of Asian patients with Crohn's disease (CD), including Bangladeshi Asians within the UK. No study has evaluated the impact of ethnicity on response to anti-TNFs. AIM Our primary endpoint was a comparison of failure-free survival on first prescribed anti-TNF (anti-tumor necrosis factor) therapy in UK Bangladeshi and Caucasian patients with CD. Our secondary aims were to evaluate disease phenotype, indication for anti-TNF prescription, and duration from diagnosis until first anti-TNF prescribed between groups. METHODS The records of consecutive outpatient appointments over a 12-month period were used to identify Caucasian and Bangladeshi patients prescribed an anti-TNF for CD. Information on patient demographics, ethnicity, disease phenotype, immunomodulator use, outcome from first biologic, duration of therapy, and reason for cessation was recorded. RESULTS In total, 224 Caucasian and Bangladeshi patients were prescribed an anti-TNF for CD. Bangladeshi patients started an anti-TNF 4.3 years earlier after diagnosis than Caucasian patients (3.9 years vs. 8.2 years: p < 0.01). Bangladeshi patients experienced shorter failure-free survival than Caucasian patients (1.8 vs. 4.8 years p < 0.01). By 2 years, significantly more Bangladeshi patients had stopped anti-TNF due to loss of response (OR 6.35, p < 0.01). CONCLUSIONS This is the first study to suggest that Bangladeshi patients resident in the UK with CD respond less well to treatment with TNF antagonists than Caucasian patients.
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Abstract
Fibrostenosis occurs in both Crohn's disease (CD) and ulcerative colitis (UC). Up to 21% of patients with CD present with strictures at diagnosis, while the rate of stenosis varies from 1% to 11% in UC. Despite the increasing use of immunomodulators and biologics in treatment, there has been no decrease in the rate of progression from inflammatory to complicated disease phenotypes (either stricturing or penetrating). The presence of stenosis is an independent risk factor for surgery in patients with CD, who are at a risk of postoperative recurrence at a rate of up to 55% at 10 years after surgery. Patients with inflammatory bowel disease (IBD) strictures are at risk of malignant transformation. Thus, surveillance colonoscopy should be offered to this group of patients. Several risk factors for the development of stricture have been identified. In CD, patients aged less than 40-years old, with perianal disease at diagnosis, who need steroids at the first flare up or have ileal disease are at the risk of developing strictures; while in UC, patients with extensive colitis and long-standing disease are at risk. Recently, microbiota signatures have also been identified as markers for stricture development. The presence of Ruminococcus spp. is associated with the development of stricture in pediatric patients with CD. In this review, we highlight the epidemiology, risk factors and natural history of fibrostenosing IBD.
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Affiliation(s)
- Joyce Wing Yan Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Li Ka Shing Institute of Health Science, Chinese University of Hong Kong, Hong Kong SAR, China
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Biologic Use Patterns and Predictors for Non-persistence and Switching of Biologics in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study. Dig Dis Sci 2020; 65:1436-1444. [PMID: 31677070 DOI: 10.1007/s10620-019-05867-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 09/26/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Data on real-life patterns of biologic use for inflammatory bowel disease (IBD) are scarce. AIMS We aimed to examine the patterns of biologic use and the factors associated with non-persistence and switching of biologics in Korean IBD patients. METHODS Using National Health Insurance claims, we collected data on patients who were diagnosed with IBD and exposed to biologics between 2010 and 2016. RESULTS Among 1838 patients with Crohn's disease (CD), 1237 and 601 started with infliximab and adalimumab, respectively. Among 1125 patients with ulcerative colitis (UC), 774, 294, and 57 initiated infliximab, adalimumab, and golimumab, respectively. Rates of non-persistence and switching were higher in UC than in CD. One- and 3-year non-persistence rates were 14.2% and 26.5% in CD and 35.4% and 53.4% in UC, respectively. One- and 3-year switching rates were 3.7% and 10.1% in CD and 15.6% and 22.0% in UC, respectively. In both CD and UC, infliximab and adalimumab initiators showed similar persistence rates, whereas adalimumab initiators had a higher risk of switching than infliximab initiators. In UC, golimumab initiators had a higher risk of non-persistence and switching than infliximab initiators. Steroid use at biologic initiation was associated with an increased risk of non-persistence and switching in both CD and UC. UC patients who started biologic treatment at tertiary hospitals were more likely to continue treatment than those who started at general hospitals/community hospitals/clinics. CONCLUSIONS In real-world clinical practice settings, discontinuation of biologics occurred frequently in IBD patients, and switching of biologics was common in UC patients.
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Hibi T, Kamae I, Pinton P, Ursos L, Iwakiri R, Hather G, Patel H. Efficacy of biologic therapies for biologic-naïve Japanese patients with moderately to severely active ulcerative colitis: a network meta-analysis. Intest Res 2020; 19:53-61. [PMID: 32312035 PMCID: PMC7873404 DOI: 10.5217/ir.2019.09146] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 03/05/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/AIMS Several biologic therapies are approved in Japan to treat moderately to severely active ulcerative colitis (UC), but there are no published comparative efficacy studies in a Japanese population. We compared the efficacy of biologics approved in Japan (adalimumab, infliximab, golimumab, and vedolizumab) for treating biologic-naïve patients with UC at their approved doses. METHODS A targeted literature review identified 4 randomized controlled trials of biologics for UC in biologicnaïve Japanese patients. For each study, efficacy outcome data from induction (weeks 6-12) and maintenance (weeks 30-60) treatment were extracted for analysis. Treatment effects on clinical response, clinical remission, and mucosal healing relative to the average placebo results across all trials were estimated using network meta-analyses followed by transformation into probabilities and odds ratios (OR). RESULTS At the end of induction, the likelihood of clinical response and clinical remission was highest with infliximab (OR: 2.12 and 2.35, respectively) and vedolizumab (OR: 2.10 and 2.32, respectively); the likelihood of mucosal healing was highest with infliximab (OR: 2.24) and adalimumab (OR: 1.86). During maintenance, the likelihood of clinical response and clinical remission was highest with vedolizumab (OR: 6.44 and 4.68, respectively) and golimumab (OR: 5.13 and 3.84, respectively); the likelihood of mucosal healing was significantly higher than placebo with all biologics. CONCLUSIONS All active treatments were efficacious compared with placebo. Infliximab and vedolizumab had the highest odds for induction of clinical response, remission, and mucosal healing. Golimumab and vedolizumab had numerically higher odds of achieving efficacy outcomes in the maintenance phase.
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Affiliation(s)
- Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Isao Kamae
- Department of Health Policy and Technology Assessment, Graduate School of Public Policy, The University of Tokyo, Tokyo, Japan
| | - Philippe Pinton
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Lyann Ursos
- Global Medical Affairs, Takeda Pharmaceuticals USA, Inc., Deerfield, IL, USA
| | - Ryuichi Iwakiri
- Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan
| | - Greg Hather
- Statistical & Quantitative Sciences, Takeda Pharmaceuticals USA, Inc., Cambridge, MA, USA
| | - Haridarshan Patel
- Department of Evidence and Value Generation, Global Medical Affairs, Takeda Pharmaceuticals USA, Inc., Deerfield, IL, USA
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Sung J. Inflammatory bowel disease: Is East really differ from West? J Gastroenterol Hepatol 2020; 35:357-358. [PMID: 32162386 DOI: 10.1111/jgh.15003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Joseph Sung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.,Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
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Mak WY, Zhao M, Ng SC, Burisch J. The epidemiology of inflammatory bowel disease: East meets west. J Gastroenterol Hepatol 2020; 35:380-389. [PMID: 31596960 DOI: 10.1111/jgh.14872] [Citation(s) in RCA: 382] [Impact Index Per Article: 76.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 09/09/2019] [Accepted: 09/12/2019] [Indexed: 12/13/2022]
Abstract
The incidence of inflammatory bowel diseases (IBD) in East has risen over the past decade to become a global disease. The increasing number of studies on the incidence and course of IBD in East has enabled us to explore East versus West differences in the epidemiology of IBD which could enhance our understanding of the heterogeneity of the disease and eventually assist in the discovery of novel therapeutic targets and design of preventive strategies. Comparison of population-based data in East and West reveals that the incidence of IBD has risen rapidly in East while plateauing in West. Furthermore, the clinical presentation and course of IBD differs between East and West with more patients in East presenting with complicated disease. Considering the scarcity of population-based data from East and the lack of studies with long durations of follow-up, it remains to be clarified whether these differences reflect true differences in disease presentation. The effects of genetic and environmental risk factors contributing to IBD also differ between Eastern and Western populations. Considering the differential effects of genetic and environmental risk factors in East and West, future studies should seek to discover novel genetic and environmental risk factors which might specifically apply to eastern populations. In this narrative review, we compare the epidemiology of IBD between eastern and western countries by summarizing evidence from population-based cohort studies in the last ten years. Furthermore, we look at differences in genetic susceptibility and environmental triggers of IBD between East and West.
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Affiliation(s)
- Wing Yan Mak
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, LKS Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong
| | - Mirabella Zhao
- Gastrounit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Siew Chien Ng
- Gastrounit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
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Abu-Sbeih H, Faleck DM, Ricciuti B, Mendelsohn RB, Naqash AR, Cohen JV, Sellers MC, Balaji A, Ben-Betzalel G, Hajir I, Zhang J, Awad MM, Leonardi GC, Johnson DB, Pinato DJ, Owen DH, Weiss SA, Lamberti G, Lythgoe MP, Manuzzi L, Arnold C, Qiao W, Naidoo J, Markel G, Powell N, Yeung SCJ, Sharon E, Dougan M, Wang Y. Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease. J Clin Oncol 2020; 38:576-583. [PMID: 31800340 PMCID: PMC7030892 DOI: 10.1200/jco.19.01674] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
PURPOSE The risk of immune checkpoint inhibitor therapy-related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn's disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event-related deaths were recorded. Anti-cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.
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Affiliation(s)
| | | | - Biagio Ricciuti
- Dana-Farber Cancer Institute, Boston, MA,University of Perugia, Perugia, Italy
| | | | | | - Justine V. Cohen
- Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Maclean C. Sellers
- Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | | | | | | | | | | | - Giulia C. Leonardi
- University of Perugia, Perugia, Italy,University of Catania, Catania, Italy
| | | | - David J. Pinato
- Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
| | | | | | - Giuseppe Lamberti
- Policlinico di Sant'Orsola University Hospital, Bologna University, Bologna, Italy
| | - Mark P. Lythgoe
- Imperial College London, Hammersmith Hospital Campus, London, United Kingdom
| | - Lisa Manuzzi
- Policlinico di Sant'Orsola University Hospital, Bologna University, Bologna, Italy
| | | | - Wei Qiao
- The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | - Nick Powell
- Kings College London, London, United Kingdom
| | | | | | - Michael Dougan
- Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Yinghong Wang
- The University of Texas MD Anderson Cancer Center, Houston, TX,Yinghong Wang, MD, PhD, Department of Gastroenterology, Hepatology, and Nutrition, Unit 1466, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail:
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Agrawal M, Burisch J, Colombel JF, C Shah S. Viewpoint: Inflammatory Bowel Diseases Among Immigrants From Low- to High-Incidence Countries: Opportunities and Considerations. J Crohns Colitis 2020; 14:267-273. [PMID: 31359034 DOI: 10.1093/ecco-jcc/jjz139] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The inflammatory bowel diseases [IBDs], inclusive of Crohn's disease [CD] and ulcerative colitis [UC], are chronic, progressive immune-mediated diseases associated with high morbidity and substantial economic impact. The pathogenesis implicates a complex interaction between environmental determinants and genetic susceptibility. Of concern, the incidence and prevalence of IBD are increasing globally, with the highest relative increase observed in developing and recently developed countries. One high-risk yet underappreciated population is immigrants from countries of low to high IBD incidence, as evidenced by epidemiologic studies demonstrating higher risk of IBD among second- versus first-generation and younger versus older immigrants from low- to high-incidence countries [LTHICs]. The reasons underlying these emerging patterns among immigrants are incompletely understood and provide enormous opportunities to better define the pathophysiology of IBD and move toward disease prevention or at least earlier diagnosis. The rapidity of this epidemiologic shift in the demographic profile of IBD, which was traditionally a disease of Caucasians in industrialized countries, strongly implicates non-genetic factors and gene-environment interactions in the pathophysiology of IBD among immigrants from LTHICs. The primary objectives of this Viewpoint are to [1] provide a focused overview of IBD epidemiology among immigrants from countries at differential IBD risk; [2] emphasize the potential to advance our understanding of IBD pathogenesis via targeted research efforts to delineate risk and protective determinants in this cohort; and [3] highlight disparities and barriers in IBD care, as well as the economic implications of the rising, yet underappreciated, disease burden among immigrants from LTHICs.
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Affiliation(s)
- Manasi Agrawal
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, Copenhagen, Denmark
| | - Jean-Frederic Colombel
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA
| | - Shailja C Shah
- Division of Gastroenterology, Vanderbilt University, Nashville TN, USA
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Genetic polymorphisms present in IL10, IL23R, NOD2, and ATG16L1 associated with susceptibility to inflammatory bowel disease in Mexican population. Eur J Gastroenterol Hepatol 2020; 32:10-16. [PMID: 31651650 DOI: 10.1097/meg.0000000000001540] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE Ulcerative colitis and Crohn's disease are the two clinical forms of inflammatory bowel disease (IBD). Diverse studies have shown the association of single nucleotide polymorphism (SNP) in molecules of the immune system and the occurrence of IBD. Here, several SNPs of the immune system with controversial results for their association with UC and CD were evaluated in a Mexican population. METHODS SNPs rs1800896, rs3024505 (IL-10); rs11209026 (IL23R); rs2066844, rs2066845 (NOD-2), and rs2241880 (ATG16L1) were assessed in 93 patients with IBD and 200 healthy controls by hybridization probes and quantitative PCR. RESULTS The AG genotype for rs1800896 was associated with an increased risk for both UC and CD (P = 0.005 and P = 0.026, respectively); whereas the AA genotype presents a negative association (P = 0.011 for UC, and 0.0038 for CD). For this SNP, G allele was associated with risk of UC (P = 0-043) but not for CD. For the rs3024505 in IL-10, T allele was associated with UC (P = 0.011). Moreover, this allele was associated with early onset of UC (P = 0.033) and with the use of steroid treatment (P = 0.019). No significant differences for NOD2 (rs2066844T and rs2066845C), IL23R (rs11209026), and ATG16L1 (rs22411880) were found between cases and controls and the homozygous TT genotype for rs2066844 and CC for rs2066845 were not observed. CONCLUSION Our results show both genotypic and phenotypic associations of IL-10 SNPs with IBD but not with the other immune-related SNPs studied in this Mexican cohort.
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Han M, Jung YS, Cheon JH, Park S. Comparison of Real-World Outcomes of Infliximab versus Adalimumab in Biologic-Naïve Korean Patients with Ulcerative Colitis: A Population-Based Study. Yonsei Med J 2020; 61:48-55. [PMID: 31887799 PMCID: PMC6938779 DOI: 10.3349/ymj.2020.61.1.48] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 11/29/2019] [Accepted: 12/02/2019] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with ulcerative colitis (UC) are extremely limited, especially in the Asian population. We compared clinically important outcomes [colectomy, UC-related emergency room (ER) visits, UC-related hospitalizations, and need for corticosteroids] for these two biologics in biologic-naïve Korean patients with UC. MATERIALS AND METHODS Using National Health Insurance claims, we collected data on patients who were diagnosed with UC and exposed to IFX or ADA between 2010 and 2016. RESULTS A total of 862 new users of biologics were included, of whom 630 were treated with IFX and 232 were treated with ADA. Over a median follow-up of 1.8 years after starting biologic therapy, there were no significant differences in the risk of colectomy [adjusted hazard ratio (aHR), 1.87; 95% confidence interval (CI), 0.30-11.63], ER visits (aHR, 1.58; 95% CI, 0.79-3.16), hospitalizations (aHR, 0.83; 95% CI, 0.59-1.17), and corticosteroid use (aHR, 1.16; 95% CI, 0.76-1.78) between IFX and ADA users. These results were stable even when only patients who used biologics for ≥6 months were analyzed. Additionally, these results were unchanged in patients treated with biologic monotherapy or combination therapy with immunomodulators. CONCLUSION In this nationwide population-based study, there was no significant difference in the risk of colectomy, ER visits, hospitalizations, and corticosteroid use between IFX and ADA users. Our findings indicate that IFX and ADA have comparable effectiveness in biologic-naïve Korean patients with UC.
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Affiliation(s)
- Minkyung Han
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.
| | - Sohee Park
- Department of Biostatistics, Graduate School of Public Health, Yonsei University, Seoul, Korea.
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Zhang M, Wang X, Jiang X, Yang X, Wen C, Zhi M, Gao X, Hu P, Liu H. Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China. MEDICAL SCIENCE MONITOR : INTERNATIONAL MEDICAL JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2019; 25:9637-9650. [PMID: 31844038 PMCID: PMC6929548 DOI: 10.12659/msm.917244] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background Although 90 susceptibility loci of Crohn’s disease (CD) have been confirmed in the Asian population, susceptibility genes for perianal fistula of CD (pCD) in this population remain unknown. This study explored susceptibility genes for CD and pCD in the Han population from South China. Material/Methods In total, 490 patients diagnosed with CD between July 2012 and June 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were included and divided into the CD group (n=240) and the pCD group (n=250). The healthy control group was composed of 260 volunteers. Peripheral blood samples were taken, and single nucleotide polymorphism (SNP) locus sequencing was used to screen for susceptibility loci. SNPs were sequenced using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Results Nine SNPs in TNFSF1 on chromosome 9 were associated with CD. Among them, the rs6478106 locus is a risk locus for CD. The distribution frequency of the T allele of the rs6478106 SNP was significantly different between cases and controls (32.49% versus 18.27%, P<0.001). Rs72553867, located in the IRGM gene on chromosome 5, rs4409764, located in the NKX2–3 gene on chromosome 10, and rs3731772, located in the AOX1 gene on chromosome 2, were susceptibility factors for pCD. Nine SNPs located in TNFSF15 on chromosome 9 were related to CD in Han individuals from Southern China. Conclusions The rs6478106 T allele is associated with the risk of CD in the investigated population. SNPs rs72553867 (IRGM gene), rs4409764 (NKX2–3 gene), and rs3731772 (AOX1 gene) increase the risk of pCD.
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Affiliation(s)
- Min Zhang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Xiaoyan Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Xiaodong Jiang
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Xiangling Yang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Chuangyu Wen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Min Zhi
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Xiang Gao
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Pinjin Hu
- Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland)
| | - Huanliang Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China (mainland).,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
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