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2. Gut virome-colonisingOrthohepadnavirusgenus is associated with ulcerative colitis pathogenesis and induces intestinal inflammationin vivo

Author

Massimino, Luca, primary, Palmieri, Orazio, additional, Facoetti, Amanda, additional, Fuggetta, Davide, additional, Spanò, Salvatore, additional, Lamparelli, Luigi Antonio, additional, D'Alessio, Silvia, additional, Cagliani, Stefania, additional, Furfaro, Federica, additional, D'Amico, Ferdinando, additional, Zilli, Alessandra, additional, Fiorino, Gionata, additional, Parigi, Tommaso Lorenzo, additional, Noviello, Daniele, additional, Latiano, Anna, additional, Bossa, Fabrizio, additional, Latiano, Tiziana, additional, Pirola, Alessandra, additional, Mologni, Luca, additional, Piazza, Rocco Giovanni, additional, Abbati, Danilo, additional, Perri, Francesco, additional, Bonini, Chiara, additional, Peyrin-Biroulet, Laurent, additional, Malesci, Alberto, additional, Jairath, Vipul, additional, Danese, Silvio, additional, and Ungaro, Federica, additional

Published
2023
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5. Development and validation of a histological index for UC

Author

Mosli, Mahmoud H, Feagan, Brian G, Zou, Guangyong, Sandborn, William J, DʼHaens, Geert, Khanna, Reena, Shackelton, Lisa M, Walker, Christopher W, Nelson, Sigrid, Vandervoort, Margaret K, Frisbie, Valerie, Samaan, Mark A, Jairath, Vipul, Driman, David K, Geboes, Karel, Valasek, Mark A, Pai, Rish K, Lauwers, Gregory Y, Riddell, Robert, Stitt, Larry W, and Levesque, Barrett G

Published
2017
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6. Gut virome-colonising Orthohepadnavirusgenus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo

Author

Massimino, Luca, Palmieri, Orazio, Facoetti, Amanda, Fuggetta, Davide, Spanò, Salvatore, Lamparelli, Luigi Antonio, D'Alessio, Silvia, Cagliani, Stefania, Furfaro, Federica, D'Amico, Ferdinando, Zilli, Alessandra, Fiorino, Gionata, Parigi, Tommaso Lorenzo, Noviello, Daniele, Latiano, Anna, Bossa, Fabrizio, Latiano, Tiziana, Pirola, Alessandra, Mologni, Luca, Piazza, Rocco Giovanni, Abbati, Danilo, Perri, Francesco, Bonini, Chiara, Peyrin-Biroulet, Laurent, Malesci, Alberto, Jairath, Vipul, Danese, Silvio, and Ungaro, Federica

Abstract

ObjectivesUlcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirusgenus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis.DesignHBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitromodels of the gut barrier. HBx-silencing experiments were performed in vitroand in vivo.ResultsHBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivoand in vivo.ConclusionThis study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

Published
2023
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8. International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease

Author

Gordon, Ilyssa O, primary, Bettenworth, Dominik, additional, Bokemeyer, Arne, additional, Srivastava, Amitabh, additional, Rosty, Christophe, additional, de Hertogh, Gert, additional, Robert, Marie E, additional, Valasek, Mark A, additional, Mao, Ren, additional, Li, Jiannan, additional, Harpaz, Noam, additional, Borralho, Paula, additional, Pai, Reetesh K, additional, Odze, Robert, additional, Feakins, Roger, additional, Parker, Claire E, additional, Guizzetti, Leonardo, additional, Nguyen, Tran, additional, Shackelton, Lisa M, additional, Sandborn, William J, additional, Jairath, Vipul, additional, Baker, Mark, additional, Bruining, David, additional, Fletcher, Joel G, additional, Feagan, Brian G, additional, Pai, Rish K, additional, and Rieder, Florian, additional

Published
2021
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9. Biosimilars in IBD: hope or expectation?

Author

Gecse, Krisztina B, Khanna, Reena, van den Brink, Gijs R, Ponsioen, Cyriel Y, Löwenberg, Mark, Jairath, Vipul, Travis, Simon P L, Sandborn, William J, Feagan, Brian G, and DʼHaens, Geert R A M

Published
2013
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13. ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study

Author

Laursen, Stig Borbjerg, primary, Oakland, Kathryn, additional, Laine, Loren, additional, Bieber, Vered, additional, Marmo, Riccardo, additional, Redondo-Cerezo, Eduardo, additional, Dalton, Harry R, additional, Ngu, Jeffrey, additional, Schultz, Michael, additional, Soncini, Marco, additional, Gralnek, Ian, additional, Jairath, Vipul, additional, Murray, Iain A, additional, and Stanley, Adrian J, additional

Published
2020
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14. Assessment of Crohn’s disease-associated small bowel strictures and fibrosis on cross-sectional imaging: a systematic review

Author

Bettenworth, Dominik, primary, Bokemeyer, Arne, additional, Baker, Mark, additional, Mao, Ren, additional, Parker, Claire E, additional, Nguyen, Tran, additional, Ma, Christopher, additional, Panés, Julián, additional, Rimola, Jordi, additional, Fletcher, Joel G, additional, Jairath, Vipul, additional, Feagan, Brian G, additional, and Rieder, Florian, additional

Published
2019
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15. Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology

Author

Oakland, Kathryn, primary, Chadwick, Georgina, additional, East, James E, additional, Guy, Richard, additional, Humphries, Adam, additional, Jairath, Vipul, additional, McPherson, Simon, additional, Metzner, Magdalena, additional, Morris, A John, additional, Murphy, Mike F, additional, Tham, Tony, additional, Uberoi, Raman, additional, Veitch, Andrew McCulloch, additional, Wheeler, James, additional, Regan, Cuthbert, additional, and Hoare, Jonathan, additional

Published
2019
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16. International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease

Author

Gordon, Ilyssa O, Bettenworth, Dominik, Bokemeyer, Arne, Srivastava, Amitabh, Rosty, Christophe, de Hertogh, Gert, Robert, Marie E, Valasek, Mark A, Mao, Ren, Li, Jiannan, Harpaz, Noam, Borralho, Paula, Pai, Reetesh K, Odze, Robert, Feakins, Roger, Parker, Claire E, Guizzetti, Leonardo, Nguyen, Tran, Shackelton, Lisa M, Sandborn, William J, Jairath, Vipul, Baker, Mark, Bruining, David, Fletcher, Joel G, Feagan, Brian G, Pai, Rish K, and Rieder, Florian

Abstract

ObjectiveEffective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion.DesignModified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures.ResultsIn this exercise, diagnosis of nai¨ve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials.ConclusionStandardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.

Published
2022
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17. ABC score: a new risk score that accurately predicts mortality in acute upper and lower gastrointestinal bleeding: an international multicentre study.

Author

Laursen, Stig Borbjerg, Oakland, Kathryn, Laine, Loren, Bieber, Vered, Marmo, Riccardo, Redondo-Cerezo, Eduardo, Dalton, Harry R., Ngu, Jeffrey, Schultz, Michael, Soncini, Marco, Gralnek, Ian, Jairath, Vipul, Murray, Iain A., and Stanley, Adrian J.

Subjects
GASTROINTESTINAL hemorrhage, ENDOSCOPIC hemostasis, RECEIVER operating characteristic curves
Published
2021
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19. Responsiveness of histological disease activity indices in ulcerative colitis: a post hoc analysis using data from the TOUCHSTONE randomised controlled trial

Author

Jairath, Vipul, primary, Peyrin-Biroulet, Laurent, additional, Zou, Guangyong, additional, Mosli, Mahmoud, additional, Vande Casteele, Niels, additional, Pai, Reetesh K, additional, Valasek, Mark A, additional, Marchal-Bressenot, Aude, additional, Stitt, Larry W, additional, Shackelton, Lisa M, additional, Khanna, Reena, additional, D’Haens, Geert R, additional, Sandborn, William J, additional, Olson, Allan, additional, Feagan, Brian G, additional, and Pai, Rish K, additional

Published
2018
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21. Responsiveness of histological disease activity indices in ulcerative colitis: a post hoc analysis using data from the TOUCHSTONE randomised controlled trial.

Author

Jairath, Vipul, Peyrin-Biroulet, Laurent, Guangyong Zou, Mosli, Mahmoud, Casteele, Niels Vande, Pai, Reetesh K., Valasek, Mark A., Marchal-Bressenot, Aude, Stitt, Larry W., Shackelton, Lisa M., Khanna, Reena, D'Haens, Geert R., Sandborn, William J., Olson, Allan, Feagan, Brian G., and Pai, Rish K.

Subjects
ULCERATIVE colitis, DATA analysis
Published
2019
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22. Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials

Author

Hindryckx, Pieter, primary, Levesque, Barrett G, additional, Holvoet, Tom, additional, Durand, Serina, additional, Tang, Ceen-Ming, additional, Parker, Claire, additional, Khanna, Reena, additional, Shackelton, Lisa M, additional, D'Haens, Geert, additional, Sandborn, William J, additional, Feagan, Brian G, additional, Lebwohl, Benjamin, additional, Leffler, Daniel A, additional, and Jairath, Vipul, additional

Published
2016
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24. Development and validation of a histological index for UC

Author

Mosli, Mahmoud H, primary, Feagan, Brian G, additional, Zou, Guangyong, additional, Sandborn, William J, additional, D'Haens, Geert, additional, Khanna, Reena, additional, Shackelton, Lisa M, additional, Walker, Christopher W, additional, Nelson, Sigrid, additional, Vandervoort, Margaret K, additional, Frisbie, Valerie, additional, Samaan, Mark A, additional, Jairath, Vipul, additional, Driman, David K, additional, Geboes, Karel, additional, Valasek, Mark A, additional, Pai, Rish K, additional, Lauwers, Gregory Y, additional, Riddell, Robert, additional, Stitt, Larry W, additional, and Levesque, Barrett G, additional

Published
2015
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27. Authors' response

Author

Logan, Richard F A, primary, Hearnshaw, Sarah, additional, Jairath, Vipul, additional, Travis, Simon, additional, and Palmer, Kelvin R, additional

Published
2011
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28. Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo .

Author

Massimino L, Palmieri O, Facoetti A, Fuggetta D, Spanò S, Lamparelli LA, D'Alessio S, Cagliani S, Furfaro F, D'Amico F, Zilli A, Fiorino G, Parigi TL, Noviello D, Latiano A, Bossa F, Latiano T, Pirola A, Mologni L, Piazza RG, Abbati D, Perri F, Bonini C, Peyrin-Biroulet L, Malesci A, Jairath V, Danese S, and Ungaro F

Subjects
Animals, Mice, Virome, Mice, Inbred C57BL, Colon pathology, Inflammation metabolism, Intestinal Mucosa metabolism, Disease Models, Animal, Dextran Sulfate, Colitis, Ulcerative pathology, Colitis metabolism
Abstract

Objectives: Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis., Design: HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo ., Results: HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo . HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo ., Conclusion: This study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments., Competing Interests: Competing interests: SD has served as a speaker, consultant and advisory board member for Schering Plough, Abbott (AbbVie) Laboratories, Merck and Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Vifor and Johnson and Johnson. LP-B has served as consultant for Merck, AbbVie, Janssen, Genentech, Ferring, Tillots, Vifor, Pharmacosmos, Celltrion, Takeda, Biogaran, Boerhinger-lngelheim, Lilly, Pfizer, Jndex Pharmaceuticals, Amgen, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestlé, Enterome, Mylan, HAC-Pharma, Tigenix, and has served as speaker for Merck, AbbVie, Janssen, Genentech, Ferring, Tillots, Vifor, Pharmacosmos, Celltrion, Takeda, Boerhinger-lngelheim, Pfizer, Amgen, Biogen, Samsung Bioepis. VJ has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Vividion; speaker’s fees from, AbbVie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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