{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:09:08Z","timestamp":1780322948159,"version":"3.54.1"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Biliary atresia (BA) is a devastating cholangiopathy of infancy. Upon diagnosis, surgical reconstruction by Kasai hepatoportoenterostomy (HPE) restores biliary drainage in a subset of patients, but most patients develop fibrosis and progress to end\u2010stage liver disease requiring liver transplantation for survival. In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling that of human BA. High\u2010mobility group box 1 (HMGB1) is an important member of the danger\u2010associated molecular patterns capable of mediating inflammation during infection\u2010associated responses. In this study, we investigated the role of HMGB1 in BA pathogenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>In cholangiocytes, RRV\u00a0induced the expression and release of HMGB1 through the p38 mitogen\u2010activated protein kinase signaling pathway, and inhibition of p38 blocked HMGB1 release. Treatment of cholangiocytes with ethyl pyruvate suppressed the release of HMGB1. Administration of glycyrrhizin <jats:italic toggle=\"yes\">in vivo<\/jats:italic> decreased symptoms and increased survival in the murine model of BA. HMGB1 levels were measured in serum obtained from infants with BA enrolled in the PROBE and START studies conducted by the Childhood Liver Disease Research Network. High HMGB1 levels were found in a subset of patients at the time of HPE. These patients had higher bilirubin levels 3\u00a0months post\u2010HPE and a lower survival of their native liver at 2\u00a0years.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>These results suggest that HMGB1 plays a role in virus induced BA pathogenesis and could be a target for therapeutic interventions in a subset of patients with BA and high HMGB1.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31745","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T12:38:51Z","timestamp":1612960731000},"page":"864-878","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":28,"title":["High Mobility Group Box 1 Release by Cholangiocytes Governs Biliary Atresia Pathogenesis and Correlates With Increases in Afflicted Infants"],"prefix":"10.1097","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8603-2876","authenticated-orcid":false,"given":"Sujit K.","family":"Mohanty","sequence":"first","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"Temple","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ortiz\u2010Perez","sequence":"additional","affiliation":[{"name":"Translational Liver Research,Department of Medical Cell Biophysics,Technical Medical Centre,Faculty of Science and Technology,University of Twente,Enschede,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mowery","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Lobeck","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phylicia","family":"Dupree","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly M.","family":"Poling","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"McNeal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University of Cincinnati College of Medicine,Cincinnati,OH"},{"name":"Division of Infectious Diseases,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Mourya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Hepatology & Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Thoracic Surgery,Cincinnati Children\u2019s Hospital Medical 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