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Moazzami B, Zabala ZE, Chandradevan R, Sifuentes H. Racial disparity in inflammatory bowel disease-related complications: a nationwide cohort study. Ann Gastroenterol 2025; 38:294-305. [PMID: 40371211 PMCID: PMC12070337 DOI: 10.20524/aog.2025.0958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 03/05/2025] [Indexed: 05/16/2025] Open
Abstract
Background Racial disparities in inflammatory bowel disease (IBD)-related complications are increasingly recognized, yet nationwide data remain limited. This study examined racial differences in IBD-related complications across diverse patient populations. Methods We analyzed data from the Nationwide Inpatient Sample 2016-2021, on over 1.7 million weighted hospitalizations for IBD. Adults with Crohn's disease (CD) or ulcerative colitis (UC) were identified using ICD-10 codes. Key outcomes included anal abscess, intestinal obstruction, rectal bleeding and anal fissure/fistula, were compared across racial groups. Multivariate logistic regression was used to estimate the odds of complications, adjusting for age, sex, insurance, comorbidities, and hospital factors. Results Compared to White patients, Black and Hispanic patients with CD had higher rates of anal abscesses (2.8% and 2.57% vs. 1.25%) and rectal bleeding (2.85% and 2.51% vs. 1.79%). Multivariate logistic regression showed that Black and Asian patients had higher odds of developing anal abscess compared to White patients (adjusted OR [aOR] 1.41, 95% confidence interval [CI] 1.38-1.45] and aOR 1.19, 95%CI 1.13-1.29, respectively). In UC, Black (aOR 1.33, 95%CI 1.29-1.37), Hispanic (aOR 1.23, 95%CI 1.21-1.27), and Asian patients (aOR 1.12, 95%CI 1.04-1.20) had higher odds of rectal bleeding, while the odds of intestinal obstruction were lower in Black (aOR 0.74, 95%CI 0.67-0.82), compared to White patients. Conclusions Racial disparities exist in complications associated with IBD. Black and Hispanic patients had higher odds of perianal complications, while White patients had more intestinal obstruction. These findings emphasize the need for earlier intervention and improved access to advanced therapies in diverse populations.
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Affiliation(s)
- Bobak Moazzami
- Rollins School of Public Health, Emory University, Atlanta, GA, USA (Bobak Moazzami)
- Internal Medicine, Graduate Medical Education-Northside Hospital Gwinnett, Lawrenceville, GA, USA (Bobak Moazzami)
| | - Zohyra E. Zabala
- Internal Medicine, St. Barnabas Hospital Health System, Bronx, NY, USA (Zohyra E. Zabala)
| | - Raguraj Chandradevan
- Department of Gastroenterology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA (Raguraj Chandradevan, Humberto Sifuentes)
| | - Humberto Sifuentes
- Department of Gastroenterology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA (Raguraj Chandradevan, Humberto Sifuentes)
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Nielsen KR, Lophaven SN, Midjord J, Langholz E, Burisch J, Hammer T. Mortality of Patients With Inflammatory Bowel Disease in the Faroe Islands From 1966-2020. Inflamm Bowel Dis 2025; 31:952-962. [PMID: 38830628 DOI: 10.1093/ibd/izae120] [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] [Received: 03/21/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND Increased mortality rates have been found in patients suffering from inflammatory bowel disease (IBD). The Faroe Islands have the highest occurrence of IBD, mainly ulcerative colitis (UC). This study investigated mortality of patients with IBD compared with the general Faroese population. METHODS All patients diagnosed with IBD from 1966-2020 were included, as well as population mortality data. All-cause and cause-specific mortality in the IBD cohort was compared with the population by standardized incidence ratios (SIRs). Risk factors for death within the cohort were assessed by hazard ratios (HRs) using Cox regression. RESULTS Overall mortality was not increased in patients with Crohn's disease (CD; SIR 0.9; 95% confidence interval [CI], 0.56-1.35) or UC (SIR 1.0; 95% CI, 0.83-1.25). However, patients with UC had an elevated risk of dying from digestive diseases (SIR 4.3; 95% CI, 2.16-7.74). Patients with IBD had lower risk of death of cardiovascular diseases compared with the background population (SIR 0.7; 95% CI, 0.50-0.93). Risk factors for mortality included male gender, age at diagnosis, and use of steroids. Protective factors were use of 5-aminosalicylic acid (5-ASA), thiopurines, and biological treatment. CONCLUSIONS No increased risk of all-cause mortality in patients with CD or UC was found in this nationwide study compared with the entire Faroese population over more than 5 decades. The risk of death due to digestive diseases was, however, increased in patients with UC, while mortality risk of cardiovascular diseases was lower in patients with IBD.
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Affiliation(s)
- Kári Rubek Nielsen
- Medical Centre, National Hospital of the Faroe Islands, Tórshavn, Faroe Islands
- Genetic Biobank, Tórshavn, Faroe Islands
- Department of Research, the National Hospital of the Faroe Islands, Tórshavn, Faroe Islands
| | | | - Jóngerð Midjord
- Medical Centre, National Hospital of the Faroe Islands, Tórshavn, Faroe Islands
- Department of Research, the National Hospital of the Faroe Islands, Tórshavn, Faroe Islands
| | - Ebbe Langholz
- Gastrounit D, Medical section, Herlev and Gentofte University Hospital, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Gastrounit, Medical Section, 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
| | - Turid Hammer
- Department of Research, the National Hospital of the Faroe Islands, Tórshavn, Faroe Islands
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Zhang Q, Wang Y, Liu S, Zhu S, Li P, Wu S. Mortality risk associated with MASLD, MASLD type and different cardiometabolic risk factors in IBD patients: A long-term prospective cohort study. Dig Liver Dis 2025; 57:744-752. [PMID: 39581836 DOI: 10.1016/j.dld.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/13/2024] [Accepted: 11/01/2024] [Indexed: 11/26/2024]
Abstract
PURPOSE To examine the mortality risk associated with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD type, lean/non-lean MASLD and different cardiometabolic risk factors (CMRFs) in patients with inflammatory bowel disease (IBD) based on a long-term prospective cohort. METHODS Prevalent IBD patients at baseline who were free of alcoholic liver disease, cancer and hepatitis B/C virus seropositive were included (N=4622). MASLD, MASLD type [pure MASLD, MASLD with increased alcohol intake (MetALD)], lean/non-lean MASLD and CMRFs at baseline were defined according to the latest criteria proposed by AASLD and EASL. Primary outcome was all-cause mortality. Cox proportional hazard model was used to examine the association. RESULTS Overall, 1,763 (38.1%) were diagnosed with MASLD. During a median of 13.3-year follow-up, 451 all-cause deaths were identified. Compared with IBD-only patients, those with MASLD had a 58% excess risk of mortality (HR=1.58, 95%CI:1.07-2.32). Furthermore, as number of CMRFs increased in MASLD patients, mortality risk was significantly increased (Ptrend=0.005), with a 85% and 83% higher risk in MASLD with 3 CMRFs (HR=1.85, 95%CI:1.20-2.85) and ≥4 CMRFs (HR=1.83, 95%CI:1.16-2.89) versus IBD-only patients. Specifically, similar elevated mortality risk was observed in either pure MASLD (HR= 1.62, 95%CI:1.09-2.43) or MetALD (HR=2.03, 95%CI:1.24-3.32). Moreover, the excess mortality risk was both indicated in lean (HR=3.14, 95%CI:1.57-6.29) and non-lean MASLD (HR=1.67, 95%CI:1.12-2.48). CONCLUSIONS MASLD, either pure MASLD or MetALD, as well as lean/non-lean MASLD, is associated with increased mortality risk in IBD patients, with greater risk as number of cardiometabolic risk factors increased and evidently higher risk in lean MASLD patients.
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Affiliation(s)
- Qian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Yutao Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Si Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China.
| | - Shanshan Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China.
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Javaid SS, Akhtar S, Hafeez A, Nofal A, Rahman S, Farooqui SK, Ahmed M, Ahmed IE, Fatima S, Javaid H, Kumar K, Singh H, Baig MA, Aziz AA, Dang AK, Shabbir MS. Trends in Mortality Due to Inflammatory Bowel Disease in the United States: A CDC WONDER Database Analysis (1999-2020). Dig Dis Sci 2025; 70:494-503. [PMID: 39746892 DOI: 10.1007/s10620-024-08803-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 12/12/2024] [Indexed: 01/04/2025]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a global health issue profoundly impacting quality of life. The United States accounts for nearly a quarter of the world's IBD patients, with the highest prevalence rates. This study aims to identify the demographic and regional trends of IBD-related mortality in the U.S. from 1999 to 2020. METHODOLOGY Our study utilized the CDC Wonder database to gather mortality data for IBD (Crohn's disease and ulcerative colitis) from 1999 to 2020. Results were presented as age-adjusted mortality rates (AAMR) per 100,000 population, with Joinpoint regression used to analyze trend changes and calculate annual percentage change (APC). RESULTS A total of 62,310 IBD-related deaths were recorded. From 1999 to 2020, AAMR for Crohn's disease increased from 0.79 to 0.97, declining from 1999 to 2018 (APC: - 0.22) but surging from 2018 onwards (APC: 11.26). Women had a higher AAMR (0.81) compared to men (0.77). The highest rates were among non-Hispanic whites (0.86), followed by non-Hispanic blacks (0.48) and Hispanics (0.21). AAMR varied by state, ranging from 0.29 in Hawaii to 1.42 in Vermont. For ulcerative colitis, AAMR rose from 0.56 in 1999 to 0.63 in 2020, following a similar trend: a decline from 1999 to 2018 (APC: - 0.37) followed by an increase (APC: 12.21). State-specific AAMR ranged from 0.14 in Hawaii to 0.67 in Oregon. CONCLUSION This study highlights a decrease in AAMR for both diseases from 1999 to 2018, followed by significant increases from 2018 to 2020, indicating a need for targeted interventions.
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Affiliation(s)
- Syed Sarmad Javaid
- Department of Medicine, University of Mississippi Medical Center, Jackson, USA.
| | | | | | - Abdullah Nofal
- Services Institute of Medical Sciences, Lahore, Pakistan
| | - Sara Rahman
- Services Institute of Medical Sciences, Lahore, Pakistan
| | | | | | | | - Saba Fatima
- Jinnah Sindh Medical University, Karachi, Pakistan
| | - Hira Javaid
- Allama Iqbal Medical College Lahore, Lahore, Pakistan
| | - Kantash Kumar
- Internal Medicine Maimonides Medical Center, New York, USA
| | | | | | - Ahmed Ali Aziz
- Department of Internal Medicine, Capital Health Regional Medical Center, Trenton, NJ, USA
| | - Ashujot K Dang
- Department of Internal Medicine, University of California Riverside School of Medicine, Riverside, USA
| | - Muhammad Shikaib Shabbir
- Department of Internal Medicine, University of California Riverside School of Medicine, Riverside, USA
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Vaezi A, Ashby T, Schweitzer M, Ghali P, Mirsaeidi M. Interstitial Lung Disease as an Emerging Contributor to Mortality in Patients With Inflammatory Bowel Disease: A Population-Based Epidemiological Study. Clin Transl Gastroenterol 2024; 15:e1. [PMID: 38822801 PMCID: PMC11421727 DOI: 10.14309/ctg.0000000000000720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/21/2024] [Indexed: 06/03/2024] Open
Abstract
INTRODUCTION We aim to investigate the contribution of interstitial lung disease (ILD) to mortality in patients with inflammatory bowel disease (IBD). METHODS We performed a comprehensive retrospective, population-based epidemiological study across the United States from 2001 to 2020, using the Wide-ranging Online Data for Epidemiologic Research database. Mortality data were classified according to the International Classification of Diseases, Tenth Revision , with the codes J84 for ILD, K50 for Crohn's disease, and K51 for ulcerative colitis. To discern patterns, age-adjusted mortality rates (AMR) were computed, stratified by sex, geographic census region, and racial/ethnic demographics. RESULTS From 2001 to 2020, there were 57,967 reported deaths among patients with IBD with an AMR per million significantly rising from 10.989 in 2001-2005 to 11.443 in 2016-2020 ( P < 0.0001). ILD was a contributor to death in 1.19% (692/57,967) of these cases, with AMR rising from 0.092 to 0.143 per million ( P = 0.010). The percentage of ILD-related deaths in the IBD population increased from 1.02% to 1.30% over 2 decades. ILD was a more common cause of death in patients with Crohn's disease than with ulcerative colitis (54.6% vs 45.4%), with a significant increase for both conditions from 2001 to 2020 ( P < 0.05). An upward trend in ILD-related mortality was observed in both sexes ( P < 0.05) and within the White population ( P = 0.010). DISCUSSION The observed increase in mortality rates due to ILD among patients with IBD is concerning and highlights a critical need for systematic ILD screening protocols within the IBD patient population to facilitate early detection and management.
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Affiliation(s)
- Atefeh Vaezi
- Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA;
| | - Tracy Ashby
- Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA;
| | - Michael Schweitzer
- Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA;
| | - Peter Ghali
- Division of Gastroenterology, University of Florida, Jacksonville, Florida, USA.
| | - Mehdi Mirsaeidi
- Division of Pulmonary, Critical Care, and Sleep Medicine, College of Medicine-Jacksonville, University of Florida, Jacksonville, Florida, USA;
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Galajda NÁ, Meznerics FA, Mátrai P, Fehérvári P, Lengyel AS, Kolonics MV, Sipos Z, Kemény LV, Csupor D, Hegyi P, Bánvölgyi A, Holló P. Reducing cardiovascular risk in immune-mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies-A systematic review and meta-analysis. J Eur Acad Dermatol Venereol 2024; 38:1070-1088. [PMID: 38433519 DOI: 10.1111/jdv.19900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 01/19/2024] [Indexed: 03/05/2024]
Abstract
Immune-mediated inflammatory disease (IMID) patients including psoriasis, inflammatory arthritides and bowel diseases have a higher risk of developing cardiovascular (CV) diseases compared to the general population. The increased CV risk may be promoted by tumour necrosis factor (TNF)-α-mediated immunological processes, which are present both in the pathomechanism of IMIDs and atherosclerosis. Our objective was to comprehensively investigate the effect of TNF inhibitors (TNFi) on CV risk compared with conventional therapies in IMIDs. The systematic literature search was conducted in three databases (MEDLINE, EMBASE, Cochrane Library) on 14 November 2022. Randomized controlled trials, cohort and case-control studies were eligible for inclusion. Outcomes consisted of the incidence of CV events, with major adverse cardiovascular events (MACE) as a main endpoint. A random-effects meta-analysis was performed by pooling fully adjusted multivariate hazard ratios (HR) and incidence rate ratios (IRR) with a 95% confidence interval (CI) comparing TNFis with conventional systemic non-biologicals (CSNBs). Of a total of 8724 search results, 56 studies were included overall, of which 29 articles were eligible for the meta-analysis, and 27 were involved in the systematic review. Including all IMIDs, the TNFi group showed a significantly reduced risk of MACE compared with the CSNB group (HR = 0.74, 95% confidence interval (CI) 0.58-0.95, p = 0.025; IRR = 0.77, 95% CI 0.67-0.88, p < 0.001). Subgroup analysis of Pso, PsA patients by pooling IRRs also confirmed the significantly decreased risk of MACE in TNFi-treated patients compared with CSNB groups (IRR = 0.79, 95% CI 0.64-0.98). The observational nature of most included studies leading to high heterogeneity represents a limitation. Based on the results, TNFis may reduce the risk of CV events compared to CSNBs. Therefore, earlier use of TNFis compared to conventional systemic agents in the therapeutic sequence may benefit CV risk in IMID patients.
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Affiliation(s)
- N Á Galajda
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - F A Meznerics
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - P Mátrai
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - P Fehérvári
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Department of Biostatistics, University of Veterinary Medicine, Budapest, Hungary
| | - A S Lengyel
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, Budapest, Hungary
| | - M V Kolonics
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - Z Sipos
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - L V Kemény
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, Budapest, Hungary
| | - D Csupor
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute of Clinical Pharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
| | - P Hegyi
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - A Bánvölgyi
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
- Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
| | - P Holló
- Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
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McHenry S, Glover M, Ahmed A, Alayo Q, Zulfiqar M, Ludwig DR, Ciorba MA, Davidson NO, Deepak P. NAFLD Is Associated With Quiescent Rather Than Active Crohn's Disease. Inflamm Bowel Dis 2024; 30:757-767. [PMID: 37454277 PMCID: PMC11491614 DOI: 10.1093/ibd/izad129] [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] [Received: 01/24/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND AND AIMS Crohn's disease (CD) confers an increased risk of nonalcoholic fatty liver disease (NAFLD), but the pathogenesis remains poorly understood. We determined if active intestinal inflammation increases the risk of NAFLD in patients with CD. METHODS Two cohorts (2017/2018 and 2020) with CD and no known liver disease were enrolled consecutively during staging magnetic resonance enterography. We quantified proton density fat fraction, MaRIA (Magnetic Resonance Index of Activity), and visceral adipose tissue. NAFLD was diagnosed when proton density fat fraction ≥5.5%. Synchronous endoscopy was graded by the Simple Endoscopic Score for CD and Rutgeerts score, while clinical activity was graded by the Harvey-Bradshaw index. Cytokine profiling was performed for the 2020 cohort. Transient elastography and liver biopsy were requested by standard of care. RESULTS NAFLD was diagnosed in 40% (n = 144 of 363), with higher prevalence during radiographically quiescent disease (odds ratio, 1.7; P = .01), independent of body mass index/visceral adipose tissue (adjusted odds ratio, 7.8; P = .03). These findings were corroborated by endoscopic disease activity, but not by aggregate clinical symptoms. Circulating interleukin-8 was independent of body mass index to predict NAFLD, but traditional proinflammatory cytokines were not. NAFLD subjects had similar liver stiffness estimates regardless of CD activity. Definitive or borderline steatohepatitis was present in most patients that underwent liver biopsy. CONCLUSIONS Quiescent CD is associated with risk of NAFLD. These findings suggest potentially distinct pathogenic mechanisms of NAFLD in patients with CD compared with the prevailing leaky gut hypothesis proposed for individuals without inflammatory bowel disease. Future validation and mechanistic studies are needed to dissect these distinct disease modifying factors.
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Affiliation(s)
- Scott McHenry
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
| | - Matthew Glover
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
| | - Ali Ahmed
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
- Inflammatory Bowel Disease Section, Washington University in St. Louis, St. Louis, MO, USA
| | - Quazim Alayo
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
- Inflammatory Bowel Disease Section, Washington University in St. Louis, St. Louis, MO, USA
| | - Maria Zulfiqar
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Daniel R Ludwig
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Matthew A Ciorba
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
- Inflammatory Bowel Disease Section, Washington University in St. Louis, St. Louis, MO, USA
| | - Nicholas O Davidson
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
| | - Parakkal Deepak
- Division of Gastroenterology, Washington University in St. Louis, St. Louis, MO, USA
- Inflammatory Bowel Disease Section, Washington University in St. Louis, St. Louis, MO, USA
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Sumida K, Shrestha P, Mallisetty Y, Thomas F, Gyamlani G, Streja E, Kalantar-Zadeh K, Kovesdy CP. Anti-Tumor Necrosis Factor Therapy and Risk of Kidney Function Decline and Mortality in Inflammatory Bowel Disease. JAMA Netw Open 2024; 7:e246822. [PMID: 38625700 PMCID: PMC11022116 DOI: 10.1001/jamanetworkopen.2024.6822] [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: 09/13/2023] [Accepted: 02/16/2024] [Indexed: 04/17/2024] Open
Abstract
Importance Inflammatory bowel disease (IBD) is associated with adverse clinical outcomes, including chronic kidney disease and mortality, due in part to chronic inflammation. Little is known about the effects of anti-tumor necrosis factor (TNF) therapy on kidney disease progression and mortality among patients with new-onset IBD. Objective To examine the association of incident use of TNF inhibitors with subsequent decline in kidney function and risk of all-cause mortality. Design, Setting, and Participants This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants were US veterans with new-onset IBD enrolled from October 1, 2004, through September 30, 2019. Data were analyzed from December 2022 to February 2024. Exposures Incident use of TNF inhibitors. Main Outcomes and Measures The main outcomes were at least 30% decline in estimated glomerular filtration rate (eGFR) and all-cause mortality. Results Among 10 689 patients (mean [SD] age, 67.4 [12.3] years; 9999 [93.5%] male) with incident IBD, 3353 (31.4%) had diabetes, the mean (SD) baseline eGFR was 77.2 (19.2) mL/min/1.73 m2, and 1515 (14.2%) were newly initiated on anti-TNF therapy. During a median (IQR) follow-up of 4.1 (1.9-7.0) years, 3367 patients experienced at least 30% decline in eGFR, and over a median (IQR) follow-up of 5.0 (2.5-8.0) years, 2502 patients died. After multivariable adjustments, incident use (vs nonuse) of TNF inhibitors was significantly associated with higher risk of decline in eGFR (adjusted hazard ratio [HR], 1.34 [95% CI, 1.18-1.52]) but was not associated with risk of all-cause mortality (adjusted HR, 1.02 [95% CI, 0.86-1.21]). Similar results were observed in sensitivity analyses. Conclusions and Relevance In this cohort study of US veterans with incident IBD, incident use (vs nonuse) of TNF inhibitors was independently associated with higher risk of progressive eGFR decline but was not associated with risk of all-cause mortality. Further studies are needed to elucidate potentially distinct pathophysiologic contributions of TNF inhibitor use to kidney and nonkidney outcomes in patients with IBD.
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Affiliation(s)
- Keiichi Sumida
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
| | - Prabin Shrestha
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
| | - Yamini Mallisetty
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
| | - Fridtjof Thomas
- Division of Biostatistics, Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis
| | - Geeta Gyamlani
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
- Nephrology Section, Memphis VA Medical Center, Memphis, Tennessee
| | - Elani Streja
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange
- Tibor Rubin Veterans Affairs Medical Center, Long Beach, California
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange
- Tibor Rubin Veterans Affairs Medical Center, Long Beach, California
| | - Csaba P. Kovesdy
- Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis
- Nephrology Section, Memphis VA Medical Center, Memphis, Tennessee
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Björner K, Chen WN, Gannavarapu VR, Axling F, Gulyas M, Halim MA, Webb DL, Hellström PM. High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival. Ups J Med Sci 2024; 28:10241. [PMID: 38187473 PMCID: PMC10770641 DOI: 10.48101/ujms.v128.10241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/09/2023] [Accepted: 12/03/2023] [Indexed: 01/09/2024] Open
Abstract
Background Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown. Aim The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC. Methods Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases. Results Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1β (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1β was higher (P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases. Conclusion Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.
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Affiliation(s)
- Kajsa Björner
- Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden
| | - Wei-Na Chen
- Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden
| | - Venkata Ram Gannavarapu
- Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden
| | - Fredrik Axling
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Miklos Gulyas
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Mohammad Abdul Halim
- Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden
| | - Dominic-Luc Webb
- Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden
| | - Per M. Hellström
- Department of Medical Sciences, Gastroenterology and Hepatology Section, Uppsala University, Uppsala, Sweden
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10
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Ghahramani S, Tamizifar B, Rajabpour V, Hosseinian SZ, Saeian S, Shahoon H, Bagheri Lankarani K. All-cause mortality of hospitalized inflammatory bowel disease patients: a multicenter study from Iran. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2024; 17:279-287. [PMID: 39308533 PMCID: PMC11413379 DOI: 10.22037/ghfbb.v17i3.2962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/14/2024] [Indexed: 09/25/2024]
Abstract
Aim In this multicenter study, we investigated all causes of mortality in hospitalized inflammatory bowel disease (IBD) patients. Background The widespread use of biologics and immune suppressive treatments, along with the longer lifespan of patients with IBD, may have changed the cause of death in this population. Knowing this may lead to better preventive and therapeutic strategies for IBD patients. Methods This cross-sectional study reviewed records of 1926 IBD patients hospitalized in referral hospitals in Isfahan and Shiraz during 2013-2021. In nine years, 84 patients, 39 from Isfahan and 45 from Shiraz, died. We retrospectively gathered data on demographic, clinical, and laboratory information, as well as the cause of death. We extracted the cause of death from the death sheets and classified it using the International Classification of Diseases (ICD-10). Using the Kaplan-Meier model, we estimated the median survival time from disease diagnosis to death. Results Males accounted for 47 (55%) of the deceased patients. The mean age of the patients was 48.63 ± 18.7 years. The mortality rates among hospitalized UC and CD patients were 7.2% and 7.8%, respectively. The median duration of admission to death was 8 days, with 19 (22.6%) of IBD patients dying on the first day of their hospital admission. Half of the cohort of deceased IBD patients had survived for 8 years following their disease diagnosis. 32.7% of all recorded causes of death were due to certain infectious diseases. The second and third most common causes of death were diseases of the digestive system and diseases of the circulatory system, including pulmonary embolism, accounting for 30.1% and 14.2%, respectively. Conclusion According to this study from Iran, infectious diseases are the leading cause of death among hospitalized IBD patients. Prevention and clinical management of pulmonary embolism in IBD patients require more careful consideration. We strongly encourage population-based cohort studies to enhance the findings.
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Affiliation(s)
- Sulmaz Ghahramani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Babak Tamizifar
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Vahid Rajabpour
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyedeh-Zeynab Hosseinian
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Samira Saeian
- Gastroenterology and Hepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hassan Shahoon
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Kamran Bagheri Lankarani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
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11
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Clinton JW, Cross RK. Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions. Clin Exp Gastroenterol 2023; 16:249-276. [PMID: 38111516 PMCID: PMC10726957 DOI: 10.2147/ceg.s360248] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023] Open
Abstract
Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.
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Affiliation(s)
- Joseph William Clinton
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond Keith Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
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12
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Capela TL, Silva VM, Freitas M, Arieira C, Gonçalves TC, de Castro FD, Magalhães J, Cotter J. Identifying inflammatory bowel disease patients at risk of metabolic dysfunction-associated fatty liver disease: usefulness of non-invasive steatosis predictive scores. BMC Gastroenterol 2023; 23:437. [PMID: 38093213 PMCID: PMC10720099 DOI: 10.1186/s12876-023-02988-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 10/05/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients have a higher risk of metabolic dysfunction-associated fatty liver disease (MAFLD) compared with the general population. However, it is not known whether available non-invasive hepatic steatosis scores are useful in predicting MAFLD in IBD patients. We aimed to analyze the performances of MAFLD screening score (MAFLD-S), Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Clinical Prediction Tool for NAFLD in Crohn's Disease (CPN-CD), in identifying MAFLD in IBD patients. METHODS A cross-sectional study was carried out including consecutive adult IBD outpatients submitted to transient elastography (TE). MAFLD criteria were assessed, and hepatic steatosis (HS) was defined by a controlled attenuation parameter (CAP) >248 dB/m using TE. MAFLD-S, FLI, HSI, and CPN-CD were calculated and their accuracy for the prediction of MAFLD was evaluated through their areas under the receiver-operating characteristic (AUROC) curves. RESULTS Of 168 patients, body mass index ≥25, type 2 diabetes mellitus, dyslipidemia and arterial hypertension were present in 76 (45.2%), 10 (6.0%), 53 (31.5%), 20 (11.9%), respectively. HS was identified in 77 (45.8%) patients, of which 65 (84.4%) fulfilled MAFLD criteria. MAFLD-S (AUROC, 0.929 [95% CI, 0.888-0.971]) had outstanding and FLI (AUROC, 0.882 [95% CI, 0.830-0.934]), HSI (AUROC, 0.803 [95% CI, 0.736-0.871]), and CPN-CD (AUROC, 0.822 [95% CI, 0.753-0.890) had excellent discrimination in predicting MAFLD. CONCLUSIONS MAFLD-S, FLI, HSI and CPN-CD scores can accurately identify MAFLD in IBD patients, allowing the selection of those in whom hepatic steatosis and metabolic risk factors assessment may be particularly beneficial.
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Affiliation(s)
- Tiago Lima Capela
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal.
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal.
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal.
| | - Vítor Macedo Silva
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
| | - Marta Freitas
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
| | - Cátia Arieira
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
| | - Tiago Cúrdia Gonçalves
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
| | - Francisca Dias de Castro
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
| | - Joana Magalhães
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
| | - José Cotter
- Hospital Senhora da Oliveira, Gastroenterology Department, Guimarães, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga/Guimarães, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Guimarães/Braga, Braga, Portugal
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13
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Li F, Ramirez Y, Yano Y, Daniel CR, Sharma SV, Brown EL, Li R, Moshiree B, Loftfield E, Lan Q, Sinha R, Inoue-Choi M, Vogtmann E. The association between inflammatory bowel disease and all-cause and cause-specific mortality in the UK Biobank. Ann Epidemiol 2023; 88:15-22. [PMID: 38013230 PMCID: PMC10842122 DOI: 10.1016/j.annepidem.2023.10.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/05/2023] [Accepted: 10/26/2023] [Indexed: 11/29/2023]
Abstract
PURPOSE Inflammatory bowel disease (IBD) has a rising global prevalence. However, the understanding of its impact on mortality remains inconsistent so we explored the association between IBD and all-cause and cause-specific mortality. METHODS This study included 502,369 participants from the UK Biobank, a large, population-based, prospective cohort study with mortality data through 2022. IBD was defined by baseline self-report or from primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality in multivariable Cox proportional hazards regression models. RESULTS A total of 5799 (1.2%) participants had a history of IBD at baseline. After a median follow-up of 13.7 years, 44,499 deaths occurred. Having IBD was associated with an increased risk of death from all causes (HR = 1.16, 95% CI = 1.07-1.24) and cancer (HR = 1.16, 95% CI = 1.05-1.30), particularly colorectal cancer (CRC) (HR = 1.56, 95% CI = 1.17-2.09). We observed elevated breast cancer mortality rates for individuals with Crohn's disease, and increased CRC mortality rates for individuals with ulcerative colitis. In stratified analyses of IBD and all-cause mortality, mortality risk differed by individuals' duration of IBD, age at IBD diagnosis, body mass index (BMI) (PHeterogeneity = 0.03) and smoking status (PHeterogeneity = 0.01). Positive associations between IBD and all-cause mortality were detected in individuals diagnosed with IBD for 10 years or longer, those diagnosed before the age of 50, all BMI subgroups except obese individuals, and in never or current, but not former smokers. CONCLUSIONS We found that having IBD was associated with increased risks of mortality from all causes, all cancers, and CRC. This underscores the importance of enhanced patient management strategies and targeted prevention efforts in individuals with IBD.
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Affiliation(s)
- Fangyu Li
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Yesenia Ramirez
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Yukiko Yano
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Carrie R Daniel
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Shreela V Sharma
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston
| | - Eric L Brown
- Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston
| | - Ruosha Li
- Department of Biostatistics and Data Science, School of Public Health, University of Texas Health Science Center at Houston
| | - Baharak Moshiree
- Division of Gastroenterology, Hepatology, and Nutrition, Atrium Health, Wake Forest University, Charlotte, NC
| | - Erikka Loftfield
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Qing Lan
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Rashmi Sinha
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Maki Inoue-Choi
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD
| | - Emily Vogtmann
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
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14
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Lewis JD, Parlett LE, Jonsson Funk ML, Brensinger C, Pate V, Wu Q, Dawwas GK, Weiss A, Constant BD, McCauley M, Haynes K, Yang JY, Schaubel DE, Hurtado-Lorenzo A, Kappelman MD. Incidence, Prevalence, and Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States. Gastroenterology 2023; 165:1197-1205.e2. [PMID: 37481117 PMCID: PMC10592313 DOI: 10.1053/j.gastro.2023.07.003] [Citation(s) in RCA: 147] [Impact Index Per Article: 73.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 06/30/2023] [Accepted: 07/07/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND & AIMS We sought to estimate the incidence, prevalence, and racial-ethnic distribution of physician-diagnosed inflammatory bowel disease (IBD) in the United States. METHODS The study used 4 administrative claims data sets: a 20% random sample of national fee-for-service Medicare data (2007 to 2017); Medicaid data from Florida, New York, Pennsylvania, Ohio, and California (1999 to 2012); and commercial health insurance data from Anthem beneficiaries (2006 to 2018) and Optum's deidentified Clinformatics Data Mart (2000 to 2017). We used validated combinations of medical diagnoses, diagnostic procedures, and prescription medications to identify incident and prevalent diagnoses. We computed pooled age-, sex-, and race/ethnicity-specific insurance-weighted estimates and pooled estimates standardized to 2018 United States Census estimates with 95% confidence intervals (CIs). RESULTS The age- and sex-standardized incidence of IBD per 100,000 person-years was 10.9 (95% CI, 10.6-11.2). The incidence of IBD peaked in the third decade of life, decreased to a relatively stable level across the fourth to eighth decades, and declined further. The age-, sex- and insurance-standardized prevalence of IBD was 721 per 100,000 population (95% CI, 717-726). Extrapolated to the 2020 United States Census, an estimated 2.39 million Americans are diagnosed with IBD. The prevalence of IBD per 100,000 population was 812 (95% CI, 802-823) in White, 504 (95% CI, 482-526) in Black, 403 (95% CI, 373-433) in Asian, and 458 (95% CI, 440-476) in Hispanic Americans. CONCLUSIONS IBD is diagnosed in >0.7% of Americans. The incidence peaks in early adulthood and then plateaus at a lower rate. The disease is less commonly diagnosed in Black, Asian, and Hispanic Americans.
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Affiliation(s)
- James D Lewis
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | | | - Michele L Jonsson Funk
- Center for Pharmacoepidemiology, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Colleen Brensinger
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Virginia Pate
- Center for Pharmacoepidemiology, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Qufei Wu
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ghadeer K Dawwas
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Alexandra Weiss
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Brad D Constant
- Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Maureen McCauley
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kevin Haynes
- Janssen Research and Development, LLC, Titusville, New Jersey
| | - Jeff Yufeng Yang
- Center for Pharmacoepidemiology, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Douglas E Schaubel
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Michael David Kappelman
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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15
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Ge X, Hu J, Peng Y, Zeng Z, He D, Li X, Chen Y, Luo G, Deng J, Xu Z, He S. Atmosphere-inspired multilayered nanoarmor with modulable protection and delivery of Interleukin-4 for inflammatory microenvironment modulation. Biomaterials 2023; 301:122254. [PMID: 37531774 DOI: 10.1016/j.biomaterials.2023.122254] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 06/26/2023] [Accepted: 07/23/2023] [Indexed: 08/04/2023]
Abstract
Inflammatory bowel disease (IBD) has been closely associated with immune disorders and excessive M1 macrophage activation, which can be reversed by the M2-polarizing effect of interleukin-4 (IL-4). However, maintaining native IL-4 activity with its specific release in the inflammatory microenvironment and efficient biological performance remain a challenge. Inspired by the multilayered defense mechanism of the earth's atmosphere, we constructed a multilayered protective nanoarmor (NA) for IL-4 delivery (termed as IL-4@PEGRA NAs) into an intricate inflammatory microenvironment. The poly(ethylene glycol) (PEG)-ylated phenolic rosmarinic acid (RA)-grafted copolymer contains two protective layers-the intermediate polyphenol (RA molecules) and outermost shield (PEG) layers-to protect the biological activity of IL-4 and prolong its circulation in blood. Moreover, IL-4@PEGRA NAs scavenge reactive oxygen species with the specific release of IL-4 and maximize its biofunction at the site of inflammation, leading to M2 macrophage polarization and downregulation of inflammatory mediators. Simultaneously, gut microbiota dysbiosis can improve to amplify the M2-polarizing effect and inhibit the phosphatidylinositol 3 kinase/Akt signaling pathway, thereby attenuating inflammation and promoting colitis tissue repair. It provides a nature-inspired strategy for constructing an advanced multilayered NA delivery system with protective characteristics and potential for IBD management.
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Affiliation(s)
- Xin Ge
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 400010, China
| | - Junfeng Hu
- Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy & Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing, 400715, China
| | - Yuan Peng
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China; Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Zhuo Zeng
- Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Danfeng He
- Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Xilan Li
- Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Yajie Chen
- Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Gaoxing Luo
- Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
| | - Jun Deng
- Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma, Burn and Combined Injury, Chongqing Key Laboratory for Disease Proteomics, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
| | - Zhigang Xu
- Key Laboratory of Luminescence Analysis and Molecular Sensing, Ministry of Education, School of Materials and Energy & Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices, Southwest University, Chongqing, 400715, China.
| | - Song He
- Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, 400010, China.
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16
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Liu B, Qin Z, Cai Z, Liu Z, Chen YL, Yin X, Yin Y, Peng X, Zhang B. Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study. Biomedicines 2023; 11:2543. [PMID: 37760983 PMCID: PMC10526051 DOI: 10.3390/biomedicines11092543] [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: 07/26/2023] [Revised: 09/07/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Observational studies suggested that inflammatory bowel disease (IBD) (i.e., Crohn's disease [CD] and ulcerative colitis [UC]) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD) and ischemic stroke. However, it is still unclear whether the observed associations causally exist. Thus, we aim to examine the potential effect of IBD, CD, and UC on the risk of CAD and ischemic stroke, using a two-sample Mendelian randomization (MR) study. METHODS Genetic instruments for IBD, CD, and UC were retrieved from the latest published genome-wide association studies (GWASs) of European ancestry. GWAS summary data for instrument-outcome associations were gathered from four independent resources: CARDIoGRAMplusC4D Consortium, MEGASTROKE consortium, FinnGen, and UK Biobank. The inverse variance weighted (IVW) method and multiple pleiotropy-robust approaches were conducted and, subsequently, combined in a fixed-effect meta-analysis. Moreover, multivariable MR (MVMR) analysis was conducted to adjust for potential influencing instrumental variables. RESULTS The IVW method revealed no causal effect of IBD on the risk of CAD (overall IBD on CAD: OR 1.003, 95%CI 0.982 to 1.025; CD on CAD: OR 0.997, 95%CI 0.978 to 1.016; UC on CAD: OR 0.986, 95%CI 0.963 to 1.010) or the risk of ischemic stroke (overall IBD on ischemic stroke: OR 0.994, 95%CI 0.970 to 1.018; CD on ischemic stroke: OR 0.996, 95%CI 0.979 to 1.014; UC on ischemic stroke: OR 0.999, 95%CI 0.978 to 1.020). The results of the meta-analysis and MVMR remained consistent. CONCLUSION Our MR analysis does not support a causal effect of IBD on CAD and ischemic stroke, and previous results from observational studies might be biased through uncontrolled confoundings (such as IBD-specific medications and detection bias, etc.) that warrant further research.
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Affiliation(s)
- Baike Liu
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Zijian Qin
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zhaolun Cai
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Zheran Liu
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yun-Lin Chen
- Department of Cardiology, The 2nd Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Xiaonan Yin
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Yuan Yin
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Xingchen Peng
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Bo Zhang
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
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Tu KC, Yu RY, Lin YH, Chien CC, Lu CL. Bidirectional association between infectious gastroenteritis and inflammatory bowel disease: a population-based study. Eur J Med Res 2023; 28:337. [PMID: 37697336 PMCID: PMC10494362 DOI: 10.1186/s40001-023-01324-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Accepted: 08/27/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Intertwined association between infectious gastroenteritis (IGE) and inflammatory bowel disease (IBD) has not been investigated clearly. We aimed to examine the bidirectional association between IGE and IBD. METHODS A bidirectional study using the Taiwan National Health Insurance Research Database was designed. Through a case-control design, we identified 2899 new IBD cases during 2006-2017 and matched to 28,990 non-IBD controls. We used conditional logistic regression model to estimate odds ratios (OR) of IBD for previous IGE in different exposure time-windows within 5-years before IBD diagnosis and Poisson regression model to estimate incidence rate ratio (IRR) of subsequent IGE for IBD group to non-IBD group. RESULTS The mean age at the initial IBD diagnosis was 41 years. More IBD patients (21.49%) than controls (12.60%) had been exposed to IGE during > 6 months to 5 years before IBD diagnosis, the OR of IBD for IGE was 1.89 [95% confidence interval: 1.69-2.11]. Excess OR decreased as IGE exposure time before the index date increased. More IGE episodes were associated with additional increase in IBD risk (OR: 1.64, 2.19, 2.57, 3.50, and 4.57 in patients with 1, 2, 3, 4, and ≥ 5 IGE episodes, respectively). The IRR of having IGE for IBD group to non-IBD group was 2.42 before IBD diagnosis and increased to 5.74 after IBD diagnosis. CONCLUSIONS These findings suggested an IGE-IBD bidirectional association. More attention is needed for physicians to develop preventive strategies and be aware of the higher risk of subsequent IGE in IBD patients.
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Affiliation(s)
- Kuan-Chieh Tu
- Department of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan
| | - Ru-Yi Yu
- Graduate Institute of Food Safety, College of Agriculture and Natural Resources, South District, National Chung Hsing University, 145 Xingda Road, Taichung, 402, Taiwan
| | - Yu-Hsuan Lin
- Graduate Institute of Food Safety, College of Agriculture and Natural Resources, South District, National Chung Hsing University, 145 Xingda Road, Taichung, 402, Taiwan
| | | | - Chin-Li Lu
- Graduate Institute of Food Safety, College of Agriculture and Natural Resources, South District, National Chung Hsing University, 145 Xingda Road, Taichung, 402, Taiwan.
- Department of Food Science and Biotechnology, College of Agriculture and Natural Resources, National Chung Hsing University, Taichung, Taiwan.
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
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18
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Magro F, Portela F, Lago P, Chagas C, Moreira F, Pereira F, Rodrigues B, Pedrosa H, Correia L. Burden of Disease and Cost of Illness of Inflammatory Bowel Diseases in Portugal. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2023; 30:283-292. [PMID: 37767302 PMCID: PMC10521318 DOI: 10.1159/000525206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 01/26/2022] [Indexed: 09/29/2023]
Abstract
Background Inflammatory bowel diseases' (IBD) increasing incidence and prevalence place a heavy health and economic burden on society. Objectives This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care. Methods The burden of disease was expressed using disability-adjusted life years (DALY). Costs were estimated considering the societal perspective, using a prevalence-based model and prices established by law. An expert panel composed of 5 expert Portuguese gastroenterologists and a patient-reported study were conducted to support the cost analysis and fill in information gaps. Results In Portugal, with a prevalence of 24,069 IBD patients and an incidence of 15/100,000, the burden of disease was estimated at 6,067 DALYs: 507 resulting from premature deaths and 5,560 from disability. Total cost was estimated at EUR 146 million per year, with direct costs representing 59%. Average yearly cost per IBD patient is EUR 6,075, where 60% is related to Crohn's disease and 40% to ulcerative colitis (UC). Conclusion This study estimates the annual health burden and cost of IBD in Portugal, thus generating information with the intent to raise awareness of the need to advance health policies as well as better clinical and economic decisions in this pathology.
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Affiliation(s)
- Fernando Magro
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
- IBD Portuguese Group (GEDII), Porto, Portugal
- Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- MedInUP − Centre for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| | - Francisco Portela
- IBD Portuguese Group (GEDII), Porto, Portugal
- Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Paula Lago
- IBD Portuguese Group (GEDII), Porto, Portugal
- Gastroenterology Department, Centro Hospitalar e Universitário do Porto, Hospital de Santo António, Porto, Portugal
| | - Cristina Chagas
- IBD Portuguese Group (GEDII), Porto, Portugal
- Gastroenterology Department, Centro Hospitalar Lisboa Ocidental, Hospital Egas Moniz, Lisboa, Portugal
| | | | | | | | | | - Luis Correia
- IBD Portuguese Group (GEDII), Porto, Portugal
- Gastroenterology Department, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, Lisboa, Portugal
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19
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McHenry S. The evaluation of liver abnormalities in inflammatory bowel disease patients. Curr Opin Gastroenterol 2023; 39:287-293. [PMID: 37144524 PMCID: PMC10421594 DOI: 10.1097/mog.0000000000000942] [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] [Indexed: 05/06/2023]
Abstract
PURPOSE OF REVIEW Develop a clinical presentation-based approach for common liver abnormalities encountered by providers caring for patients with inflammatory bowel disease (IBD). Develop a treatment pathway for those with nonalcoholic fatty liver disease (NAFLD) arising in IBD. Discuss recent studies of prevalence, incidence, risk factors, and prognosis NAFLD in the IBD population. RECENT FINDINGS The work-up for liver abnormalities should be approached systematically in IBD patients, similar to the general population, while still appreciating the differing prevalence of underlying liver diagnoses. Although immune mediated liver diseases occur commonly in patients with IBD, NAFLD is still the most common liver disease in patients with IBD paralleling its expanding prevalence in the general population. IBD is also an independent risk factor for NAFLD, developing in many patients with lower degrees of adiposity. Furthermore, the more severe histologic subtype, nonalcoholic steatohepatitis, is both more common and difficult to treat considering the lower effectiveness of weight loss interventions. SUMMARY Having a standard approach to the most common liver disease presentations and care pathway for NAFLD will improve the quality of care provided and ease the medical decision making complexity for IBD patients. The early identification of these patients should prevent the development of irreversible complications like cirrhosis or hepatocellular carcinoma.
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Affiliation(s)
- Scott McHenry
- Division of Gastroenterology, Hepatology Section, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
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20
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Burisch J. Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort. APMIS 2023; 131 Suppl 147:1-46. [PMID: 37336790 DOI: 10.1111/apm.13334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
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21
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BARTOŠKA P, PALUCH Z. Treatment of Crohn's disease. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2022. [DOI: 10.23736/s0393-3660.22.04819-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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22
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Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease. Life (Basel) 2022; 12:life12101623. [PMID: 36295058 PMCID: PMC9604584 DOI: 10.3390/life12101623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/07/2022] [Accepted: 10/08/2022] [Indexed: 11/16/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals’ genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.
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23
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Trifan A, Stafie R, Rotaru A, Stratina E, Zenovia S, Nastasa R, Huiban L, Cuciureanu T, Muzica C, Chiriac S, Girleanu I, Singeap AM, Sfarti C, Cojocariu C, Petrea O, Stanciu C. Screening for Liver Steatosis and Fibrosis in Patients with Inflammatory Bowel Disease Using Vibration Controlled Transient Elastography with Controlled Attenuation Parameter. J Clin Med 2022; 11:5959. [PMID: 36233826 PMCID: PMC9573563 DOI: 10.3390/jcm11195959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/01/2022] [Accepted: 10/07/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are frequently associated with extraintestinal manifestations, hepatic injury being of concern in these patients. Current literature reports an increased prevalence of liver steatosis and fibrosis in subjects with IBD and the pathophysiology is yet to be completely understood. The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with IBD, as well as to determine the factors that connect these two disorders. METHODS From September 2021 to June 2022, 82 consecutive IBD patients were enrolled from a tertiary care center hospital in Iasi. Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter (CAP) was used to assess the presence of NAFLD, with a cut-off score for CAP of 248 dB/m. Significant liver fibrosis was considered at a cut-off for liver stiffness measurements (LSM) of 7.2 kPa. RESULTS In total, 82 IBD patients (54.8% men, mean age of 49 ± 13 years) were included, 38 (46.3%) of them being diagnosed with NAFLD, with a mean CAP score of 286 ± 35.4 vs. 203 ± 29.7 in patients with IBD only. Age (β = 0.357, p = 0.021), body mass index (BMI) (β = 0.185, p = 0.048), disease duration (β = 0.297, p = 0.041), C-reactive protein (β = 0.321, p = 0.013), fasting plasma glucose (β = 0.269, p = 0.038), and triglycerides (β = 0.273, p = 0.023) were strongly associated with the presence of liver steatosis. The multivariate analysis showed that older age, BMI, and disease duration were strongly associated with significant liver fibrosis in our group. CONCLUSIONS NAFLD is a multifaced pathology with growing prevalence among IBD patients. Additional studies are needed to completely understand this problem and to create a solid evidence-based framework for more effective preventative and intervention strategies.
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Affiliation(s)
- Anca Trifan
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Remus Stafie
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Adrian Rotaru
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ermina Stratina
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Sebastian Zenovia
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Robert Nastasa
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Laura Huiban
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Cristina Muzica
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Stefan Chiriac
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Oana Petrea
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
| | - Carol Stanciu
- Department of Gastroenterology, Grigore T. Popa University of Medicine and Pharmacy, 70015 Iasi, Romania
- Institute of Gastroenterology and Hepatology, “St. Spiridon” University Hospital, 700111 Iasi, Romania
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Pavlidis P, Tsakmaki A, Pantazi E, Li K, Cozzetto D, Digby-Bell J, Yang F, Lo JW, Alberts E, Sa ACC, Niazi U, Friedman J, Long AK, Ding Y, Carey CD, Lamb C, Saqi M, Madgwick M, Gul L, Treveil A, Korcsmaros T, Macdonald TT, Lord GM, Bewick G, Powell N. Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy. Nat Commun 2022; 13:5820. [PMID: 36192482 PMCID: PMC9530232 DOI: 10.1038/s41467-022-33331-8] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 09/14/2022] [Indexed: 11/28/2022] Open
Abstract
The function of interleukin-22 (IL-22) in intestinal barrier homeostasis remains controversial. Here, we map the transcriptional landscape regulated by IL-22 in human colonic epithelial organoids and evaluate the biological, functional and clinical significance of the IL-22 mediated pathways in ulcerative colitis (UC). We show that IL-22 regulated pro-inflammatory pathways are involved in microbial recognition, cancer and immune cell chemotaxis; most prominently those involving CXCR2+ neutrophils. IL-22-mediated transcriptional regulation of CXC-family neutrophil-active chemokine expression is highly conserved across species, is dependent on STAT3 signaling, and is functionally and pathologically important in the recruitment of CXCR2+ neutrophils into colonic tissue. In UC patients, the magnitude of enrichment of the IL-22 regulated transcripts in colonic biopsies correlates with colonic neutrophil infiltration and is enriched in non-responders to ustekinumab therapy. Our data provide further insights into the biology of IL-22 in human disease and highlight its function in the regulation of pathogenic immune pathways, including neutrophil chemotaxis. The transcriptional networks regulated by IL-22 are functionally and clinically important in UC, impacting patient trajectories and responsiveness to biological intervention.
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Affiliation(s)
| | - Anastasia Tsakmaki
- Diabetes Research Group, School of Life Course Sciences, Faculty of Life Science and Medicine, King's College London, London, UK
| | - Eirini Pantazi
- School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Katherine Li
- Janssen Research & Development, 1400 McKean Rd, Spring House, PA, 19477, USA
| | - Domenico Cozzetto
- Translational Bioinformatics, National Institute for Health Research Biomedical Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK
| | - Jonathan Digby-Bell
- School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Feifei Yang
- Janssen Research & Development, 1400 McKean Rd, Spring House, PA, 19477, USA
| | - Jonathan W Lo
- Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK
| | - Elena Alberts
- School of Immunology and Microbial Sciences, King's College London, London, UK
| | | | - Umar Niazi
- Translational Bioinformatics, National Institute for Health Research Biomedical Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK
| | - Joshua Friedman
- Janssen Research & Development, 1400 McKean Rd, Spring House, PA, 19477, USA
| | - Anna K Long
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Yuchun Ding
- Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, UK
| | - Christopher D Carey
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, UK
| | - Christopher Lamb
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Framlington Place, Newcastle upon Tyne, UK
| | - Mansoor Saqi
- Translational Bioinformatics, National Institute for Health Research Biomedical Centre, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK
| | - Matthew Madgwick
- Earlham Institute, Norwich Research Park, Norwich, UK
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Leila Gul
- Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK
- Earlham Institute, Norwich Research Park, Norwich, UK
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Agatha Treveil
- Earlham Institute, Norwich Research Park, Norwich, UK
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Tamas Korcsmaros
- Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK
- Earlham Institute, Norwich Research Park, Norwich, UK
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Thomas T Macdonald
- Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, QMUL, London, UK
| | - Graham M Lord
- School of Immunology and Microbial Sciences, King's College London, London, UK
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Gavin Bewick
- Diabetes Research Group, School of Life Course Sciences, Faculty of Life Science and Medicine, King's College London, London, UK
| | - Nick Powell
- Division of Digestive Diseases, Faculty of Medicine, Imperial College London, London, UK.
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25
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Nardone OM, Iacucci M. Image-Enhanced Endoscopy in the Surveillance of Colitis-Associated Neoplasia. Gastrointest Endosc Clin N Am 2022; 32:845-862. [PMID: 36202520 DOI: 10.1016/j.giec.2022.05.012] [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] [Indexed: 02/04/2023]
Abstract
Advances in endoscopic technology have allowed for improved detection and management of dysplasia. These developments have also raised the question of the optimal methods for surveillance. Promising data showed that virtual chromoendoscopy (VCE) is comparable to dye-based chromoendoscopy (DCE). However, the usefulness of DCE and VCE in the surveillance of longstanding inflammatory bowel disease colitis when compared with high-definition white-light endoscopy has been recently questioned. Confocal laser endomicroscopy is a highly innovative endoscopic procedure but is still far from the routine adoption for surveillance. Thus, a personalized approach should guide the most appropriate surveillance strategy.
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Affiliation(s)
- Olga Maria Nardone
- Institute of Immunology and Immunotherapy, Heritage Building for Research and Development, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TT, United Kingdom.
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, Heritage Building for Research and Development, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham B15 2TT, United Kingdom.
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26
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Pribadi RR, Simadibrata M, Sulaiman AS, Abdullah M. Role of thigh circumference, calf circumference, subjective global assessment, and handgrip strength as diagnostic modalities of sarcopenia in women inflammatory bowel disease patients. JGH Open 2022; 6:621-624. [PMID: 36091320 PMCID: PMC9446409 DOI: 10.1002/jgh3.12797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 03/12/2022] [Accepted: 07/11/2022] [Indexed: 11/24/2022]
Abstract
Background and Aim Sarcopenia is a problem affecting inflammatory bowel disease (IBD) outcome and should be evaluated by measuring muscle mass (using dual‐energy X‐ray absorptiometry [DXA]), muscle strength, and physical performance. DXA has drawbacks as it is expensive, not covered by a national program, and requires a technician. Other inexpensive and simple examinations are needed. The objective is to explore cutoff point and diagnostic accuracy of thigh circumference (TC), calf circumference (CC), subjective global assessment (SGA), and handgrip strength (HGS) to identify sarcopenia in IBD patients. Methods The study was conducted in Cipto Mangunkusumo Hospital during November 2020–June 2021. Analysis was performed to discover the cutoff point and diagnostic accuracy of TC, CC, SGA, and HGS to identify sarcopenia. Results As assessed by DXA, 7 of 60 women (11.7%) with IBD had sarcopenia. Using CC cutoff ≤31 cm, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ration (PLR), and negative likelihood ratio (NLR) were 100%, 60.38%, 25%, 100%, 2.52, and 0, respectively. Using TC cutoff ≤50 cm, the sensitivity, specificity, PPV, NPV, PLR, and NLR were 100%, 83.02%, 43.75%, 100%, 5.90, and 0, respectively. SGA has sensitivity, specificity, PPV, NPV, PLR, and NLR of 42.86%, 84.91%, 27.27%, 91.84%, 2.84, and 0.67, respectively. The area under curve of HGS was 33.3%. Conclusion In this survey of Indonesian women with IBD, the frequency of sarcopenia was 11.7%. When compared with DXA, TC and CC values over 50 cm and 31 cm, respectively, were helpful to exclude the diagnosis of sarcopenia. SGA and HGS were of lesser value for the identification of a decrease in muscle mass.
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Affiliation(s)
- Rabbinu Rangga Pribadi
- Division of Gastroenterology, Pancreatobiliary, and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo National Central General Hospital Jakarta Indonesia
| | - Marcellus Simadibrata
- Division of Gastroenterology, Pancreatobiliary, and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo National Central General Hospital Jakarta Indonesia
| | - Andri Sanityoso Sulaiman
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo National Central General Hospital Jakarta Indonesia
| | - Murdani Abdullah
- Division of Gastroenterology, Pancreatobiliary, and Digestive Endoscopy, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo National Central General Hospital Jakarta Indonesia
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27
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Kleinjans M, Schneider CV, Bruns T, Strnad P. Phenome of coeliac disease vs. inflammatory bowel disease. Sci Rep 2022; 12:14572. [PMID: 36028550 PMCID: PMC9418215 DOI: 10.1038/s41598-022-18593-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 08/16/2022] [Indexed: 11/09/2022] Open
Abstract
Coeliac disease (CeD) is characterized by gliadin-induced intestinal inflammation appearing in genetically susceptible individuals, such as HLA-DQ2.5 carriers. CeD, as well as other chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis, has been associated with increased morbidity and mortality, but the causes are unknown. We systematically analysed CeD-associated diagnoses and compared them to conditions enriched in subjects with CD/UC as well as in HLA-DQ2.5 carriers without CeD. We compared the overall and cause-specific mortality and morbidity of 3,001 patients with CeD, 2,020 with CD, 4,399 with UC and 492,200 controls in the community-based UK Biobank. Disease-specific phenotypes were assessed with the multivariable Phenome Wide Association Study (PheWAS) method. Associations were adjusted for age, sex and body mass index. All disease groups displayed higher overall mortality than controls (CD: aHR = 1.91[1.70-2.17]; UC: aHR = 1.32 [1.20-1.46]; CeD: aHR = 1.38 [1.22-1.55]). Cardiovascular and cancer-related deaths were responsible for the majority of fatalities. PheWAS analysis revealed 166 Phecodes overrepresented in all three disorders, whereas only ~ 20% of enriched Phecodes were disease specific. Seven of the 58 identified CeD-specific Phecodes were enriched in individuals homozygous for HLA-DQ2.5 without diagnosed CeD. Four out of these seven Phecodes and eight out of 19 HLA-DQ2.5 specific Phecodes were more common in homozygous HLA-DQ2.5 subjects with vs. without CeD, highlighting the interplay between genetics and diagnosis-related factors. Our study illustrates that the morbidity and mortality in CeD share similarities with CD/UC, while the CeD-restricted conditions might be driven by both inherited and acquired factors.
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Affiliation(s)
- Moritz Kleinjans
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Carolin V Schneider
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
- The Institute for Translational Medicine and Therapeutics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Tony Bruns
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Pavel Strnad
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
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28
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Dang AK, Gonzalez DA, Kumar R, Asif S, Bali A, Anne KK, Konanur Srinivasa NK. Vinculum of Cardiovascular Disease and Inflammatory Bowel Disease: A Narrative Review. Cureus 2022; 14:e26144. [PMID: 35891823 PMCID: PMC9303831 DOI: 10.7759/cureus.26144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/20/2022] [Indexed: 11/24/2022] Open
Abstract
Inflammatory bowel disease (IBD), comprising of ulcerative colitis (UC) and Crohn's disease (CrD), is a chronic relapsing-remitting inflammation of the bowel with extraintestinal involvement. Numerous studies published in the last decade have underlined the dangerous cardiovascular disease (CVD) outcomes of IBD, such as ischemic heart disease, heart failure, and stroke, and the need for better therapeutic and prognostic strategies. This article elucidated the pathological web of mechanisms that link IBD with CVD, such as immune dysregulation, endothelial dysfunction, arterial stiffness, and dysbiosis, with a comprehensive review of clinical studies standing for and against the notion in pediatric and adult populations. The current treatment and prevention aim at disease remission and dietary strategies shown to reduce the CVD risk. Exploration of other supplemental preventive and treatment methods, especially during active flares of disease, to reduce the risk of arterial thromboembolic disease (ATED) is the need of the hour.
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29
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Weissman S, Systrom HK, Aziz M, El-Dallal M, Lee-Smith W, Sciarra M, Feuerstein JD. Colorectal Cancer Prevention in Inflammatory Bowel Disease: A Systematic Analysis of the Overall Quality of Guideline Recommendations. Inflamm Bowel Dis 2022; 28:745-754. [PMID: 34245270 DOI: 10.1093/ibd/izab164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Owing to the increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD), numerous societies developed preventative guidelines. We aimed to assess the overall quality of CRC prevention guidelines in IBD. METHODS A systematic search was performed in multiple databases to identify all guidelines pertaining to CRC prevention in IBD in September 2020. All guidelines were reviewed for conflicts of interest (COIs)/funding, recommendation quality/strength, external guideline review, use of patient representation, and plans for update-as per Institute of Medicine standards. In addition, recommendations were compared amongst societies. RESULTS One hundred forty-nine recommendations from 14 different guidelines/societies were included. Not all guidelines provided recommendations on key elements surrounding (1) screening initiation and surveillance, (2) screening modality, (3) pharmacological chemoprevention, (4) dysplasia management and follow-up, and (5) molecular marker use. Only 71% of guidelines disclosed COIs, 43% reported industry funding, 14% were externally reviewed, 7% included patient representation, and 36% had plans for update. Of the total recommendations, 7.4%, 23.5%, and 69.1% were based on high,- moderate-, and low-quality evidence, respectively. Additionally, 20.1% of recommendations were strong, 14.1%, were weak/conditional, and 65.8% did not provide a strength. The proportion of high-quality evidence (P = 0.34) and strong recommendations (P = 0.57) did not significantly differ across societies. CONCLUSIONS Many guidelines do not provide recommendations on key aspects of CRC prevention in IBD. Over 90% of recommendations are based on low- to moderate-quality evidence; therefore, further studies on CRC prevention in IBD are needed to improve the overall quality of evidence.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, New Jersey, USA
| | - Hannah K Systrom
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo Medical Center, Toledo, OH, USA
| | - Mohammed El-Dallal
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Division of Hospital Medicine, Cambridge Health Alliance, Cambridge and Harvard Medical School, MA, USA
| | - Wade Lee-Smith
- Department of Library Sciences, University of Toledo Medical Center, Toledo, OH, USA
| | - Michael Sciarra
- Division of Gastroenterology and Hepatology, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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30
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Stallmach A, Grunert P, Stallhofer J, Löffler B, Baier M, Rödel J, Kiehntopf M, Neugebauer S, Pieper DH, Junca H, Tannapfel A, Merkel U, Schumacher U, Breternitz-Gruhne M, Heller T, Schauer A, Hartmann M, Steube A. Transfer of FRozen Encapsulated multi-donor Stool filtrate for active ulcerative Colitis (FRESCO): study protocol for a prospective, multicenter, double-blind, randomized, controlled trial. Trials 2022; 23:173. [PMID: 35193638 PMCID: PMC8861997 DOI: 10.1186/s13063-022-06095-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 02/07/2022] [Indexed: 11/10/2022] Open
Abstract
Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (<0.2 μm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable. Methods Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12. Discussion This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease. Trial registration ClinicalTrials.govNCT03843385. DRKS (Deutsches Register für Klinische Studien) DRKS00020471
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Affiliation(s)
- Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany.
| | - Philip Grunert
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Johannes Stallhofer
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
| | - Bettina Löffler
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Michael Baier
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Jürgen Rödel
- Institute of Medical Microbiology, Jena University Hospital, Friedrich Schiller University, Jena, Germany
| | - Michael Kiehntopf
- Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Jena, Germany
| | - Sophie Neugebauer
- Institute for Clinical Chemistry and Laboratory Diagnostics and Integrated Biobank Jena, Jena University Hospital, Jena, Germany
| | - Dietmar H Pieper
- Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection, Braunschweig, Germany
| | - Howard Junca
- Microbial Interactions and Processes Research Group, Helmholtz Centre for Infection, Braunschweig, Germany
| | | | - Ute Merkel
- Hospital Pharmacy, Jena University Hospital, Jena, Germany
| | - Ulrike Schumacher
- Center for Clinical Studies Jena (ZKS), Jena University Hospital, Jena, Germany
| | | | - Tabitha Heller
- Center for Clinical Studies Jena (ZKS), Jena University Hospital, Jena, Germany
| | - Anja Schauer
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
| | | | - Arndt Steube
- Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University of Jena, Am Klinikum 1, 07747, Jena, Germany
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31
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Zhulina Y, Udumyan R, Tysk C, Halfvarson J. Mortality in patients with Crohn's disease in Örebro, Sweden 1963-2010. Scand J Gastroenterol 2022; 57:158-164. [PMID: 34693837 DOI: 10.1080/00365521.2021.1991466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Some studies have suggested a reduced life expectancy in patients with Crohn's disease (CD) compared with the general population. The evidence, however, is inconsistent. AIMS Prompted by such studies, we studied survival of CD patients in Örebro county, Sweden. METHODS From the medical records, we identified all patients diagnosed with CD during 1963-2010 with follow-up to the end of 2011. We estimated: overall survival, net and crude probabilities of dying from CD, relative survival ratio (RSR), and excess mortality rate ratios (EMRR) at 10-year follow-up. RESULTS The study included 492 patients (226 males, 266 females). Median age at diagnosis was 32 years (3-87). Net and crude probabilities of dying from CD increased with increasing age and were higher for women. Net survival of patients aged ≥60 at diagnosis was worse for patients diagnosed during 1963-1985 (54%) than for patients diagnosed during 1986-1999 (88%) or 2000-2010 (93%). Overall, CD patients' survival was comparable to that in the general population [RSR = 0.98; 95% CI: (0.95-1.00)]. However, significantly lower than expected survival was suggested for female patients aged ≥60 diagnosed during the 1963-1985 [RSR = 0.47 (0.07-0.95)]. The adjusted model suggested that, compared with diagnostic period 1963-1985, disease-related excess mortality declined during 2000-2010 [EMRR = 0.36 (0.07-1.96)]; and age ≥60 at diagnosis [EMRR = 7.99 (1.64-39.00), reference: age 40-59], female sex [EMRR = 4.16 (0.62-27.85)], colonic localization [EMRR = 4.20 (0.81-21.88), reference: ileal localization], and stricturing/penetrating disease [EMRR = 2.56 (0.52-12.58), reference: inflammatory disease behaviour] were associated with poorer survival. CONCLUSION CD-related excess mortality may vary with diagnostic period, age, sex and disease phenotype.Key summaryThere is inconsistent evidence on life expectancy of patients with Crohn's diseaseCrohn's disease-specific survival improved over time.Earlier diagnosis period, older age at diagnosis, female sex, colonic disease and complicated disease behaviour seems to be associated with excess Crohn's disease-related mortality.
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Affiliation(s)
- Yaroslava Zhulina
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Ruzan Udumyan
- Clinical Epidemiology and Biostatistics; School of Medical Sciences, Örebro University, Örebro, Sweden
| | - Curt Tysk
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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Colorectal Cancer Surveillance in Patients with Inflammatory Bowel Diseases: Chromoendoscopy or Non-Chromoendoscopy, That Is the Question. J Clin Med 2022; 11:jcm11030509. [PMID: 35159961 PMCID: PMC8836765 DOI: 10.3390/jcm11030509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 01/03/2022] [Accepted: 01/17/2022] [Indexed: 12/07/2022] Open
Abstract
Subjects affected by ulcerative colitis and Crohn’s disease with colonic localization have an increased risk of colorectal cancer (CRC). Surveillance colonoscopy is recommended by international guidelines as it can detect early-stage CRC. Based on previous evidence, in 2015 the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients International Consensus indicated dye chromoendoscopy (DCE) as the most effective technique for detecting dysplasia. However, advances in endoscopic technology such as high-definition colonoscopes and dye-less virtual chromoendoscopy (VCE) may change future practice. In this review, we summarize the available evidence on CRC surveillance in IBD, focusing on the emerging role of high-definition white light endoscopy (HD-WLE) and VCE over the standard DCE, and the current role of random biopsies.
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33
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Faye AS, Colombel JF. Aging and IBD: A New Challenge for Clinicians and Researchers. Inflamm Bowel Dis 2022; 28:126-132. [PMID: 33904578 DOI: 10.1093/ibd/izab039] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Indexed: 12/12/2022]
Abstract
Evidence from recent epidemiological data suggests that the patient population with inflammatory bowel disease (IBD) is chronologically aging. As these individuals become older, cellular senescence leads to a state of chronic inflammation. This process, known as inflammaging, is thought to be closely linked with biological aging and may be upregulated within IBD. As a consequence, we see an increased risk of aging-related disorders within IBD. In addition, we see that frailty, which results from physiologic decline, is increasing in prevalence and is associated with adverse clinical outcomes in IBD. As such, in this review we explore the potential overlapping biology of IBD and aging, discuss the risk of aging-related disorders in IBD, and describe frailty and its relation to clinical outcomes within IBD. Finally, we discuss current considerations for clinical care and potential research avenues for further investigation.
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Affiliation(s)
- Adam S Faye
- Department of Medicine, Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jean-Frederic Colombel
- Department of Medicine, Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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34
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Agca R, Smulders Y, Nurmohamed M. Cardiovascular disease risk in immune-mediated inflammatory diseases: recommendations for clinical practice. Heart 2022; 108:73-79. [PMID: 33674356 PMCID: PMC8666803 DOI: 10.1136/heartjnl-2019-316378] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Affiliation(s)
- Rabia Agca
- Rheumatology, Amsterdam UMC and Reade, Amsterdam, Noord-Holland, The Netherlands
| | - Yvo Smulders
- Internal Medicine, Amsterdam UMC, Amsterdam, Noord-Holland, The Netherlands
| | - Michael Nurmohamed
- Rheumatology, Amsterdam UMC and Reade, Amsterdam, Noord-Holland, The Netherlands
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35
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Lichtenstein GR, Shahabi A, Seabury SA, Lakdawalla DN, Espinosa OD, Green S, Brauer M, Baldassano RN. Increased Lifetime Risk of Intestinal Complications and Extraintestinal Manifestations in Crohn's Disease and Ulcerative Colitis. Gastroenterol Hepatol (N Y) 2022; 18:32-43. [PMID: 35505770 PMCID: PMC9053498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Patients with Crohn's disease (CD) or ulcerative colitis (UC) have high morbidity rates owing to debilitating intestinal complications and extraintestinal manifestations (EIMs). We retrospectively identified patients in the Truven MarketScan databases with an incident CD or UC diagnosis from January 2008 to September 2015 to quantify the incremental lifetime risk of experiencing an intestinal complication or EIM after CD or UC diagnosis. Seven intestinal complications and 13 categories of EIMs by site were identified, and lifetime risk of experiencing an intestinal complication or EIM from age at CD or UC diagnosis to end of life was estimated using parametric models. Results were compared with controls' propensity score matched by age, sex, health plan, and pre-index Charlson Comorbidity Index. The CD or UC incremental risk was calculated using the difference in rates between CD or UC patients and matched controls. A total of 34,692 CD patients and 48,196 UC patients with 1:1 matched controls were included. CD and UC patients had an increased lifetime risk of intestinal complications, which varied across ages, inflammatory bowel disease (IBD) types, and categories of intestinal complications and EIMs. CD and UC patients aged 0 to 11 years had the highest incremental lifetime risk for all 7 intestinal complications and the majority of EIMs, with blood EIMs associated with the highest incremental risk (CD: 32%; UC: 21%). CD and UC patients of all ages have a higher lifetime risk of experiencing intestinal complications and EIMs than patients without CD or UC. When evaluating the burden of disease on patients with IBD, it is important to include the burden of these intestinal complications and EIMs in the assessment.
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Affiliation(s)
- Gary R. Lichtenstein
- Department of Medicine, Center for Inflammatory Bowel Disease, Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ahva Shahabi
- Health Policy and Economics, Precision Health Economics, Los Angeles, California
| | - Seth A. Seabury
- Pharmaceutical and Health Economics, Leonard D. Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles, California
| | - Darius N. Lakdawalla
- Pharmaceutical and Regulatory Innovation, Leonard D. Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles, California
| | | | - Sarah Green
- Health Policy and Economics, Precision Health Economics, Los Angeles, California
| | - Michelle Brauer
- Health Policy and Economics, Precision Health Economics, Los Angeles, California
| | - Robert N. Baldassano
- Center for Pediatric Inflammatory Bowel Disease, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
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Kim HM, Kim JH, Lee JK, Kang DR, Kim H, Kim SY, Kim HS. Age- and sex-specific risk of colorectal cancer in incident ulcerative colitis during the first 10 years after diagnosis: a nationwide population-based study. Scand J Gastroenterol 2021; 56:1279-1285. [PMID: 34376117 DOI: 10.1080/00365521.2021.1958370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE We assessed the risk of colorectal cancer (CRC) in patients with ulcerative colitis (UC) using the nationwide population-based claims data. MATERIALS AND METHODS We analyzed the claims data of the Korean National Health Insurance (2006-2015). UC and CRC were defined using ICD-10 codes and UC-specific prescriptions in this study. Age- and sex-matched individuals without UC were randomly selected from the general population. Hazard ratios (HRs), adjusted for different covariates, were calculated using multivariate Cox proportional hazard regression. RESULTS In total, 30,546 and 88,829 individuals with and without UC, respectively, were enrolled. CRC developed in 85 (0.27%) among UC, and 340 (0.38%) among individuals without UC, respectively. The HR (95% confidence interval [CI]) of CRC in all UC patients was 0.74 (0.58-0.94). Further, UC patients were stratified according to sex (male vs. female: 0.60 [0.44-0.82] vs. 1.10 [0.75-1.61]) and age (HR = 14.37, 2.74, 0.58, and 0.70 for 0-19, 20-39, 40-59, and ≥60 years, respectively). HR was significantly higher for late-onset UC (≥60 years) than for early-onset UC (0-19 years). The long duration of 5-aminosalicylic acid use had a significantly low HR, with reference to the 1st quartile. CONCLUSIONS The risk of CRC varies with age and sex in Korean patients with UC during the first decade after diagnosis. Early-onset UC (<40 years) increases the CRC risk.
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Affiliation(s)
- Hee Man Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Ji Hoon Kim
- Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jung Kuk Lee
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Dae Ryong Kang
- Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hyunil Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Su Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
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Manka P, Sydor S, Wase N, Best J, Brandenburg M, Hellbeck A, Schänzer J, Vilchez-Vargas R, Link A, Figge A, Jähnert A, von Arnim U, Coombes JD, Cubero FJ, Kahraman A, Kim MS, Kälsch J, Kinner S, Faber KN, Moshage H, Gerken G, Syn WK, Friedman SL, Canbay A, Bechmann LP. Anti-TNFα treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status. Liver Int 2021; 41:2646-2658. [PMID: 34219348 DOI: 10.1111/liv.15003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/04/2021] [Accepted: 06/21/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analysed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis. METHODS This cross-sectional study evaluated patients with established CD, with and without anti-TNFα treatment, analysing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP) and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analysed gut microbiota composition and mediators of bile acid (BA) signalling via stool and serum analysis. RESULTS Patients on anti-TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels. CONCLUSIONS Anti-TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterations in FXR-signalling (eg FGF19) and microbiota composition in CD.
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Affiliation(s)
- Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Svenja Sydor
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Nishikant Wase
- Biomolecular Analysis Facility, University of Virginia, School of Medicine, Charlottesville, VA, USA
| | - Jan Best
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Malte Brandenburg
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Annika Hellbeck
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Julia Schänzer
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Ramiro Vilchez-Vargas
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke-University Hospital Magdeburg, Magdeburg, Germany
| | - Alexander Link
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke-University Hospital Magdeburg, Magdeburg, Germany
| | - Anja Figge
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Andreas Jähnert
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Ulrike von Arnim
- Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke-University Hospital Magdeburg, Magdeburg, Germany
| | - Jason D Coombes
- Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Francisco-Javier Cubero
- Department of Immunology, Ophthalmology and ORL, Complutense University School of Medicine, Madrid, Spain
- 12 de Octubre Health Research Institute (imas 12), Madrid, Spain
| | - Alisan Kahraman
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Moon-Sung Kim
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Julia Kälsch
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Sonja Kinner
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Klaas-Nico Faber
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Han Moshage
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Guido Gerken
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
- Section of Gastroenterology, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA
- Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Vizcaya, Spain
| | - Scott L Friedman
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ali Canbay
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Lars P Bechmann
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
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Ludvigsson JF, Holmgren J, Grip O, Halfvarson J, Askling J, Sachs MC, Olén O. Adult-onset inflammatory bowel disease and rate of serious infections compared to the general population: a nationwide register-based cohort study 2002-2017. Scand J Gastroenterol 2021; 56:1152-1162. [PMID: 34369254 DOI: 10.1080/00365521.2021.1924259] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/13/2021] [Accepted: 04/26/2021] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To investigate absolute and relative risk of serious infections in adult/elderly inflammatory bowel disease (IBD) diagnosed 2002-2017. METHODS Nationwide, register-based cohort study of Swedish patients with IBD compared with general population matched reference individuals with regard to time to first serious infection, equal to hospital admission. Multivariable Cox regression estimated hazard ratios (HRs) for any serious infection. Secondary outcomes included site-specific infections, opportunistic infections and sepsis. RESULTS We identified 47 798 individuals with IBD. During a follow-up of 329 000 person-years, they had 8752 first serious infections (26.6 per 1000 person-years). This compared with an incidence rate of 10.7 per 1000 person-years in matched reference individuals, corresponding to a 2.53-fold increased hazard of serious infections (95%CI = 2.47-2.59). The HR for serious infection in elderly-onset IBD was 2.01 (95%CI = 1.95-2.08). The relative hazard of serious infection was somewhat higher in Crohn's disease (2.94; 95%CI = 2.81-3.06) than in ulcerative colitis (2.24; 95%CI = 2.17-2.31). The HR for serious infections was high in the first year of follow-up (5.17; 95%CI = 4.93-5.42). Individuals with IBD were at a particularly high relative hazard of gastrointestinal and opportunistic infections. The HR for sepsis was 2.47 (95%CI = 2.32-2.63). The relative rates for serious infections in IBD increased in recent years. CONCLUSIONS Patients with adult-onset IBD are at increased risk of serious infections, particularly gastrointestinal and opportunistic infections. Relative rates were highest just after IBD diagnosis, and seem to have increased in recent years.
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Affiliation(s)
- Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
- Department of Pediatrics, Orebro University Hospital, Orebro, Sweden
- Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Johanna Holmgren
- Department of Gastroenterology, Skåne University Hospital, Malmö, Sweden
| | - Olof Grip
- Department of Gastroenterology, Skåne University Hospital, Malmö, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Johan Askling
- Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Michael C Sachs
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden
| | - Ola Olén
- Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
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Fujita M, Suzuki H, Fukai F. Involvement of integrin-activating peptides derived from tenascin-C in colon cancer progression. World J Gastrointest Oncol 2021; 13:980-994. [PMID: 34616507 PMCID: PMC8465449 DOI: 10.4251/wjgo.v13.i9.980] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 06/03/2021] [Accepted: 08/11/2021] [Indexed: 02/06/2023] Open
Abstract
Tenascin-C (TNC) is an adhesion modulatory protein present in the extracellular matrix that is highly expressed in several malignancies, including colon cancer. Although TNC is considered a negative prognostic factor for cancer patients, the substantial role of the TNC molecule in colorectal carcinogenesis and its malignant progression is poorly understood. We previously found that TNC has a cryptic functional site and that a TNC peptide containing this site, termed TNIIIA2, can potently and persistently activate beta1-integrins. In contrast, the peptide FNIII14, which contains a cryptic bioactive site within the fibronectin molecule, can inactivate beta1-integrins. This review presents the role of TNC in the development of colitis-associated colorectal cancer and in the malignant progression of colon cancer, particularly the major involvement of its cryptic functional site TNIIIA2. We propose new possible prophylactic and therapeutic strategies based on inhibition of the TNIIIA2-induced beta1-integrin activation by peptide FNIII14.
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Affiliation(s)
- Motomichi Fujita
- Department of Molecular Patho-Physiology, Tokyo University of Science, Noda 278-8510, Chiba, Japan
| | - Hideo Suzuki
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Fumio Fukai
- Department of Molecular Patho-Physiology, Tokyo University of Science, Noda 278-8510, Chiba, Japan
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40
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Elamin S, Cohen J. Telenutrition for Inflammatory Bowel Disease: A Tipping Point for Dietary Wellness. CROHNS & COLITIS 360 2021; 3:otab017. [PMID: 34485904 PMCID: PMC8394826 DOI: 10.1093/crocol/otab017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis,
cause inflammation of the digestive tract. It is estimated that about three
million Americans and, globally, over six million individuals, suffer from IBD.
While most physicians, especially gastroenterologists, are experts in the
function and pathology of the gastrointestinal tract, factors such as nutrition
science education and training, bandwidth, culture, language, and the
longitudinal nature of dietary care, represent some of the barriers to receiving
optimal nutritional guidance. Remote dietary expert counseling, an emerging
solution that has been further highlighted by the COVID-19 pandemic, can improve
IBD patients’ nutritional status, avoid food triggers, and reduce the
frequency and severity of exacerbations. Inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis,
causes inflammation of the digestive tract. Remote nutritional expert care can
improve IBD patients’ nutritional status, avoid food triggers, and reduce
the frequency and severity of exacerbations.
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Affiliation(s)
- Sami Elamin
- Hospital Medicine Unit, Department of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.,Harvard Medical School, Boston, Massachusetts, USA
| | - Jonah Cohen
- Harvard Medical School, Boston, Massachusetts, USA.,Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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Ritaccio G, Stoleru G, Abutaleb A, Cross RK, Shetty K, Sakiani S, Wong U. Nonalcoholic Fatty Liver Disease Is Common in IBD Patients However Progression to Hepatic Fibrosis by Noninvasive Markers Is Rare. Dig Dis Sci 2021; 66:3186-3191. [PMID: 32894439 PMCID: PMC7936981 DOI: 10.1007/s10620-020-06588-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries and an increasing cause of end-stage liver disease and hepatocellular carcinoma. NAFLD is known to coexist in patients with inflammatory bowel disease (IBD). This study aims to examine the prevalence of NAFLD, as well as trends in NAFLD-associated fibrosis, in a well-characterized IBD cohort utilizing a validated noninvasive test. METHODS We conducted a single-center retrospective chart review of patients at a large academic IBD center between 2007 and 2017. Patients with IBD and concurrent hepatic steatosis were identified. Charts were reviewed for baseline characteristics and laboratory data in order to calculate and trend NAFLD progression over time by a noninvasive marker, the NAFLD fibrosis score (NFS). RESULTS Of 207 patients with IBD and concurrent NAFLD, NFS was able to be calculated for 138 patients at index diagnosis. A subsequent NFS was able to be calculated at 5-year follow-up for 56 patients. Over 5 years, 9 patients (16%) had worsening in NFS category, 4 patients (7%) had improvement in NFS category, and the remaining 43 patients (77%) stayed within their index NFS category. CONCLUSIONS IBD patients with NAFLD tend to have stable liver disease over 4-6 years, and the risk of liver disease progression is low. This is the first study to document the progression of NAFLD by noninvasive testing over time.
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Affiliation(s)
- Gabrielle Ritaccio
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA
| | - Gianna Stoleru
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA
| | - Ameer Abutaleb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Raymond K Cross
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Kirti Shetty
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Sasan Sakiani
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Uni Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA.
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Weissman S, Sharma, S, Fung BM, Aziz M, Sciarra M, Swaminath A, Feuerstein JD. Increased Mortality and Healthcare Costs Upon Hospital Readmissions of Ulcerative Colitis Flares: A Large Population-Based Cohort Study. CROHN'S & COLITIS 360 2021; 3:otab029. [PMID: 36776672 PMCID: PMC9802231 DOI: 10.1093/crocol/otab029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Ulcerative colitis (UC) flares often result in prolonged hospitalization and considerable mortality. Nevertheless, large-scale analyses evaluating the frequency and characteristics of hospital readmissions for UC remain limited. We aimed to examine these clinical outcomes in a nationwide cohort of patients hospitalized with UC. METHODS We queried the 2017 Nationwide Readmission Database using ICD-10-CM codes to identify all adult patients admitted for UC. Outcomes including mortality, readmission rates, predictors of readmission and mortality, and healthcare usage were assessed. Multivariate analysis was used to adjust for potential confounders. RESULTS From the 31,063 patients hospitalized for UC, 17.38% were readmitted within 30 days and 28.51% in 90 days. UC accounted for 28.17% and 29.82% of readmissions at 30 and 90 days, respectively. Compared to index admission, 30- and 90-day readmissions were characterized by significantly higher mortality (0.42% vs 1.99% and 1.65%, respectively), longer hospital stays (5.05 vs 6.62 and 6.04 days, respectively), and increased hospital cost ($49,999 vs $62,288 and $59,698, respectively) (all P < 0.01). Numerous factors, including chronic steroid use [hazard ratio (HR) 1.35] and opioid use (HR 1.6, were independently associated with increased 30-day readmission (P < 0.01). Numerous factors, including anxiety (HR 1.21) and venous thromboembolism (HR 5.39), were independently associated with increased 30-day mortality (P < 0.01). CONCLUSIONS In a large cohort of patients hospitalized for UC, we found that readmission is associated with higher mortality and more lengthy/costly admissions. Additionally, we found independent associations for readmission and mortality that may help identify patients who can benefit from close postdischarge follow-up.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, New Jersey, USA
| | - Sachit Sharma,
- Department of Medicine, University of Toledo Medical Center, Toledo, Ohio, USA
| | - Brian M Fung
- Division of Gastroenterology and Hepatology, University of Arizona College of Medicine—Phoenix, Phoenix, Arizona, USA
| | - Muhammad Aziz
- Division of Gastroenterology, University of Toledo Medical Center, Toledo, Ohio, USA
| | - Michael Sciarra
- Department of Gastroenterology and Hepatology, Hackensack Meridian Health Palisades Medical Center, North Bergen, New Jersey, USA
| | - Arun Swaminath
- Division of Gastroenterology, Inflammatory Bowel Disease Program, Lenox Hill Hospital, New York, New York, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Rao J, Shao L, Lin M, Huang J, Fan L. LncRNA UCA1 Accelerates the Progression of Ulcerative Colitis via Mediating the miR-331-3p/BRD4 Axis. Int J Gen Med 2021; 14:2427-2435. [PMID: 34140798 PMCID: PMC8203302 DOI: 10.2147/ijgm.s304837] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 04/06/2021] [Indexed: 12/30/2022] Open
Abstract
Background Ulcerative colitis (UC) has become one of the fastest-growing severe diseases worldwide with high morbidity. This research aimed to explore the function of lncRNA UCA1 in UC progression. Methods RT-qPCR analysis was used to examine the expression of UCA1 level in colonic mucosa tissues of UC patients. Then, fetal human cells (FHCs) were stimulated by LPS to induce inflammatory injury. CCK-8, flow cytometry and ELISA were adopted to determine the influence of UCA1 depletion on cell viability, apoptosis and pro-inflammatory factors levels in LPS-induced FHCs. The interaction between UCA1 and miR-331-3p or BRD4 was confirmed by luciferase reporter assay. The expressions of key factors involved in NF-κB pathway were assessed by Western blotting. Results LncRNA UCA1 level was elevated in colonic mucosa tissues of UC patients. LPS stimulation restrained cell viability and promoted the apoptosis and inflammatory factors levels, thus inducing FHCs inflammatory injury, while these effects were partially abolished by UCA1 knockdown. Moreover, it was found that UCA1 silence improved LPS-triggered cell injury via miR-331-3p. In addition, BRD4 was directly targeted by miR-331-3p, and BRD4 deficiency neutralized the effects of miR-331-3p repression on LPS-triggered injury in LPS-treated FHCs. Conclusion Our data determined that UCA1 knockdown attenuated UC development via targeting the miR-331-3p/BRD4/NF-κB pathway.
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Affiliation(s)
- Jun Rao
- Department of Gastroenterology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, People's Republic of China
| | - Lihua Shao
- Department of Gastroenterology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, People's Republic of China
| | - Min Lin
- Department of Gastroenterology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, People's Republic of China
| | - Jin Huang
- Department of Gastroenterology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, People's Republic of China
| | - Li Fan
- Department of Gastroenterology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, People's Republic of China
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Comorbid Diabetes in Inflammatory Bowel Disease Predicts Adverse Disease-Related Outcomes and Infectious Complications. Dig Dis Sci 2021; 66:2005-2013. [PMID: 32617771 DOI: 10.1007/s10620-020-06439-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 06/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Diabetes mellitus (DM) and inflammatory bowel diseases (IBD) are chronic systemic illnesses associated with chronic inflammation, dysbiosis, impaired immune function, and infection risk. The impact of DM in modifying disease activity in patients with IBD remains largely unknown. AIM To investigate the impact of DM on IBD-related disease outcomes, mortality, and infections in patients with IBD. METHODS We performed a longitudinal cohort analysis. Using a large institutional database, patients with concurrent IBD and DM (IBD-DM), and IBD without DM (IBD cohort), were identified and followed longitudinally to evaluate for primary (IBD-related) and secondary (mortality and infections) outcomes. Cox proportional hazards models were used to determine the independent effect of DM on each outcome, adjusting for confounding effects of covariates. RESULTS A total of 901 and 1584 patients were included in the IBD-DM and DM cohorts. Compared with IBD, IBD-DM had significantly higher risk of IBD-related hospitalization [adjusted hazard ratio (HR) 1.97, 95% confidence interval (1.71-2.28)], disease flare [HR 2.05 (1.75-2.39)], and complication [HR 1.54 (1.29-1.85)]. No significant difference was observed in the incidence of IBD-related surgery. All-cause mortality, sepsis, Clostridioides difficile infection (CDI), pneumonia, urinary tract infection, and skin infection were also more frequent in the IBD-DM than the IBD cohort (all p ≤ 0.05). Subgroup analysis of Crohn's disease (CD) and ulcerative colitis patients showed similar associations, except with an additional risk of surgery and no association with CDI in the CD-DM cohort. CONCLUSION Comorbid diabetes in patients with IBD is a predictor of poor disease-related and infectious outcomes.
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Beelen EMJ, van der Woude CJ, Pierik MJ, Hoentjen F, de Boer NK, Oldenburg B, van der Meulen AE, Ponsioen CIJ, Dijkstra G, Bruggink AH, Erler NS, Schouten WR, de Vries AC. Decreasing Trends in Intestinal Resection and Re-Resection in Crohn's Disease: A Nationwide Cohort Study. Ann Surg 2021; 273:557-563. [PMID: 31188225 DOI: 10.1097/sla.0000000000003395] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To assess time trends in intestinal resection and re-resection in Crohn's disease (CD) patients. SUMMARY OF BACKGROUND DATA CD treatment has changed considerably over the past decades. The effect of these advances on the necessity of intestinal resections and the risk of re-resection is unclear. METHODS In this nationwide cohort study, adult CD patients with ileocolonic, small bowel, colon, or rectum resections between 1991 and 2015 were included. Data were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Time trends were analyzed with a broken stick model and Cox proportional hazard model with smoothing splines. RESULTS The identified cohort comprised 8172 CD patients (3293/4879 male/female) in whom 10,315 intestinal resections were performed. The annual intestinal resection rate decreased nonlinearly from 1.9/100,000 (1991) to 0.2/100,000 (2015). A significantly steeper-decrease was observed before 1999 (slope –0.13) as compared to subsequent years (slope –0.03) (p<0.001). Analogous trends were observed for ileocolonic, small bowel, and colon resections. Overall cumulative risk of re-resection was 10.9% at 5 years, 18.6% at 10 years, and 28.3% at 20 years after intestinal resection. The hazard for intestinal re-resection showed a nonlinear decreasing trend, with hazard ratio 0.39 (95% confidence interval 0.36-0.44) in 2000 and hazard ratio 0.25 (95% confidence interval 0.18-0.34) in 2015 as compared to 1991. CONCLUSION Over the past 25 years, intestinal resection rate has decreased significantly for ileocolonic, small bowel, and colonic CD. In addition, current postoperative CD patients are at 75% lower risk of intestinal re-resection.
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Affiliation(s)
- Evelien M J Beelen
- Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands
| | - C Janneke van der Woude
- Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands
| | - Marie J Pierik
- Maastricht University Medical Center, Department of Gastroenterology and Hepatology, Maastricht, the Netherlands
| | - Frank Hoentjen
- Radboud University Medical Center, Department of Gastroenterology and Hepatology, Nijmegen, the Netherlands
| | - Nanne K de Boer
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism Research Institute, Amsterdam, The Netherlands
| | - Bas Oldenburg
- University Medical Center Utrecht, Department of Gastroenterology and Hepatology, Utrecht, the Netherlands
| | - Andrea E van der Meulen
- Leiden University Medical Center, Department of Gastroenterology and Hepatology, Leiden, the Netherlands
| | - Cyriel I J Ponsioen
- Amsterdam UMC, Academic Medical Center, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands
| | - Gerard Dijkstra
- University of Groningen, Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, the Netherlands
| | - Annette H Bruggink
- PALGA, Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands, Houten, the Netherlands
| | - Nicole S Erler
- Erasmus University Medical Center, Department of Biostatistics, Rotterdam, the Netherlands
| | - W Rudolph Schouten
- Erasmus University Medical Center, Department of Surgery, Rotterdam, the Netherlands
| | - Annemarie C de Vries
- Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Rotterdam, the Netherlands
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Phisalprapa P, Kositamongkol C, Limsrivilai J, Aniwan S, Charatcharoenwitthaya P, Pisespongsa P, Kitiyakara T, Treepongkaruna S, Chaiyakunapruk N. Cost-effectiveness and budget impact analysis of infliximab and its biosimilar in patients with refractory moderate-to-severe Crohn's disease using real world evidence in Thailand. J Med Econ 2020; 23:1302-1310. [PMID: 32729347 DOI: 10.1080/13696998.2020.1803889] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIMS This study aimed to conduct a cost-effectiveness analysis of infliximab and its biosimilar compared to conventional therapy in refractory moderate-to-severe Crohn's disease (CD) in Thailand. MATERIALS AND METHODS A Markov model was used to estimate lifetime costs and health benefits of infliximab from a societal perspective. Our analyses consisted of three choices of treatment (conventional therapy, infliximab originator, and biosimilar) and three treatment scenarios (infliximab 2 years and 3 years if relapse, infliximab 2 years and lifelong if relapse, and infliximab lifelong). The input parameters were obtained from the CD registry and systematic literature reviews. The results were reported as incremental cost-effectiveness ratios (ICERs) in 2017 USD per quality-adjusted life year (QALY) gained. The sensitivity analyses were performed to assess the influence of parameter uncertainty. Threshold sensitivity analyses were carried out to determine the optimal drug prices. Finally, budget impact analyses were conducted. RESULTS None of the scenarios was cost-effective at Thai willingness-to-pay threshold (4,706 USD/QALY gained). The lowest ICER of 30,121 USD/QALY gained was reported in the scenario that included only standard dose of infliximab biosimilar with the maximum of 5-year treatment. The drug prices need to be reduced by at least 72% to allow infliximab biosimilar to be cost-effective. The 5-year budget impact was only 695,958 USD for the current biosimilar price. CONCLUSIONS Infliximab for the treatment of refractory moderate-to-severe CD in Thailand would be cost-effective if the drug prices were significantly decreased. The best value for money strategy was infliximab biosimilar with a restricted duration of treatment. Key points The use of infliximab and its biosimilar in a restricted duration of maximum 5-year is not cost-effective for patients with moderate-to-severe Crohn's disease refractory to conventional therapy, unless their price was lowered around 72-90% in Thailand. The estimated budget impact for adopting infliximab or its biosimilar for such indication has potential financial feasibility. Policy makers may consider cost-effectiveness and budget impact findings as well as other aspects such as rarity of disease as a part of the decision making process.
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Affiliation(s)
- Pochamana Phisalprapa
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chayanis Kositamongkol
- Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Satimai Aniwan
- Gastroenterology Unit, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Phunchai Charatcharoenwitthaya
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | - Taya Kitiyakara
- Division of Gastroenterology and Hepatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Suporn Treepongkaruna
- Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Weissman S, Sinh P, Mehta TI, Thaker RK, Derman A, Heiberger C, Qureshi N, Amrutiya V, Atoot A, Dave M, Tabibian JH. Atherosclerotic cardiovascular disease in inflammatory bowel disease: The role of chronic inflammation. World J Gastrointest Pathophysiol 2020; 11:104-113. [PMID: 32832194 PMCID: PMC7403753 DOI: 10.4291/wjgp.v11.i5.104] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 04/24/2020] [Accepted: 06/27/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) causes systemic vascular inflammation. The increased risk of venous as well as arterial thromboembolic phenomena in IBD is well established. More recently, a relationship between IBD and atherosclerotic cardiovascular disease (ASCVD) has been postulated. Systemic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, have well characterized cardiac pathologies and treatments that focus on prevention of disease associated ASCVD. The impact of chronic inflammation on ASCVD in IBD remains poorly characterized. This manuscript aims to review and summarize the current literature pertaining to IBD and ASCVD with respect to its pathophysiology and impact of medications in order to encourage further research that can improve understanding and help develop clinical recommendations for prevention and management of ASCVD in patients with IBD.
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Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Preetika Sinh
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, United States
| | - Tej I Mehta
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57108, United States
| | - Rishi K Thaker
- Department of Medicine, New York Presbyterian, Brooklyn, NY 11215, United States
| | - Abraham Derman
- Department of Medicine, Mount Sinai-Saint Luke’s Roosevelt, NY 10025, United States
| | - Caleb Heiberger
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57108, United States
| | - Nabeel Qureshi
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Viralkumar Amrutiya
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Adam Atoot
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Maneesh Dave
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, CA 95817, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
- David Geffen School of Medicine at UCLA, Los Angeles, CA 90001, United States
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King D, Rees J, Mytton J, Harvey P, Thomas T, Cooney R, Patel P, Trudgill N. The Outcomes of Emergency Admissions With Ulcerative Colitis Between 2007 and 2017 in England. J Crohns Colitis 2020; 14:764-772. [PMID: 31714573 DOI: 10.1093/ecco-jcc/jjz185] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS Patients with ulcerative colitis [UC] may present as emergencies and require rapid escalation of therapy. This study aimed to assess the mortality, colectomy, and readmission risks, during and following a first emergency admission with UC. METHODS Using Hospital Episode Statistics, subjects aged between 18 and 60 years, coded with a first emergency admission with UC, were identified between 2007 and 2017. Influences of demographic factors, comorbidity, anti-tumour necrosis factor [TNF] therapy, and provider UC activity on mortality and colectomy were examined. RESULTS A total of 10 051 subjects (46% female; median age 33 years [interquartile range [IQR] 25-44]) were identified. Mortality was 0.2% in hospital and 0.5% at 12 months and, following colectomy during acute admission, it was 1.4% in hospital and 2.1% at 12 months. Females had reduced risk of colectomy during admission: odds ratio [OR] 0.73 (95% confidence interval [CI] 0.62-0.85). Comparing the period 2007-2011 with 2012-2017, the rate of colectomy fell during acute admissions: OR 0.85 [0.72-0.99], p = 0.038 and at 12 months after admission: OR 0.73 [0.61-0.87]. Anti-TNF therapy increased 4-fold in acute UC admissions from 2007-2017. Those receiving anti-TNF therapy had a 70% increased risk of colectomy during index admission compared with those not receiving anti-TNF: OR 1.72 [1.29-2.31]. Increased time to colectomy during first admission was associated with female sex: hazard ratio [HR] 0.84 [0.72-0.98] and Asian ethnicity: HR 0.61 [0.44-0.85], whereas reduced time was associated with increased comorbidity, lower deprivation, and high provider volume of colectomies for UC: HR 1.59 [1.31-1.93]. CONCLUSIONS Mortality following colectomy was 1.4% in hospital and 2.1% at 12 months, and no significant change over time was observed. Colectomy during emergency admission for UC was less common in females. Rates of anti-TNF therapy during emergency admission for UC have increased and overall colectomy rates have fallen. PODCAST This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.
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Affiliation(s)
- Dominic King
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - James Rees
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Jemma Mytton
- Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Philip Harvey
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
| | - Tom Thomas
- Department of Gastroenterology, Queen Elizabeth Hospital, Birmingham, UK
| | - Rachael Cooney
- Department of Gastroenterology, Queen Elizabeth Hospital, Birmingham, UK
| | - Prashant Patel
- Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Nigel Trudgill
- Department of Gastroenterology, Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
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49
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King D, Reulen RC, Thomas T, Chandan JS, Thayakaran R, Subramanian A, Gokhale K, Bhala N, Nirantharakumar K, Adderley NJ, Trudgill N. Changing patterns in the epidemiology and outcomes of inflammatory bowel disease in the United Kingdom: 2000-2018. Aliment Pharmacol Ther 2020; 51:922-934. [PMID: 32237083 DOI: 10.1111/apt.15701] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 12/01/2019] [Accepted: 03/09/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. AIMS To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases. METHODS Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index. RESULTS Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). CONCLUSIONS The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls.
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Affiliation(s)
- Dominic King
- Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK.,Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Raoul C Reulen
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Tom Thomas
- Translational Gastroenterology Unit, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
| | - Joht Singh Chandan
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Rasiah Thayakaran
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | | | - Krishna Gokhale
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Neeraj Bhala
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | | | - Nicola J Adderley
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Nigel Trudgill
- Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, UK
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50
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Olén O, Askling J, Sachs MC, Neovius M, Smedby KE, Ekbom A, Ludvigsson JF. Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964-2014. Gut 2020; 69:453-461. [PMID: 31092591 DOI: 10.1136/gutjnl-2018-317572] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 04/09/2019] [Accepted: 04/30/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years. DESIGN Swedish nationwide register-based cohort study 1964-2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873. RESULTS During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn's disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002-2014 had 2.3 years shorter mean estimated life span than matched comparators. CONCLUSIONS Adult-onset and elderly-onset patients with UC, Crohn's disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.
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Affiliation(s)
- Ola Olén
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.,Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
| | - Johan Askling
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Michael C Sachs
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Martin Neovius
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Karin E Smedby
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Anders Ekbom
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA
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