{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:56:34Z","timestamp":1772207794259,"version":"3.50.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Ischaemic Hepatitis (IH) or Hypoxic Hepatitis (HH) also known as centrilobular liver cell necrosis is an acute liver injury characterized by a rapid increase in serum aminotransferase. The liver injury typically results from different underlying medical conditions such as cardiac failure, respiratory failure and septic shock in which the liver becomes damaged due to deprivation of either blood or oxygen. IH is a potentially lethal condition that is often preventable if diagnosed timely. The role of mechanisms that cause IH is often not well understood, making it difficult to diagnose or accurately quantify the patterns of related biomarkers. In most patients, currently, the only way to determine a case of IH is to rule out all other possible conditions for liver injuries. A better understanding of the liver\u2019s response to IH is necessary to aid in its diagnosis, measurement, and improve outcomes. The goal of this study is to identify mechanisms that can alter associated biomarkers for reducing the density of damaged hepatocytes, and thus reduce the chances of IH. We develop a mathematical model capturing dynamics of hepatocytes in the liver through the rise and fall of associated liver enzymes aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) related to the condition of IH. The model analysis provides a novel approach to predict the level of biomarkers given variations in the systemic oxygen in the body. Using IH patient data in the US, novel model parameters are described and then estimated for the first time to capture real-time dynamics of hepatocytes in the presence and absence of IH condition. The results may allow physicians to estimate the extent of liver damage in an IH patient based on their enzyme levels and receive faster treatment on a real-time basis.<\/jats:p>","DOI":"10.1371\/journal.pone.0230833","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T15:32:39Z","timestamp":1619105559000},"page":"e0230833","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["The role of oxygen intake and liver enzyme on the dynamics of damaged hepatocytes: Implications to ischaemic liver injury via a mathematical model"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4239-0038","authenticated-orcid":true,"given":"Aditi","family":"Ghosh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Onsager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Mason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Arriola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuj","family":"Mubayi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"issue":"7","key":"pone.0230833.ref001","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/j.1478-3231.2011.02655.x","article-title":"Hypoxic hepatitis","volume":"32","author":"J Henrion","year":"2012","journal-title":"Liver International"},{"issue":"6","key":"pone.0230833.ref002","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1097\/01.md.0000101573.54295.bd","article-title":"Hypoxic hepatitis: Clinical and Hemodynamic Study in 142 Consecutive Cases","volume":"82","author":"J Henrion","year":"2003","journal-title":"Medicine"},{"issue":"5-6","key":"pone.0230833.ref003","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00508-010-1357-6","article-title":"Hypoxic hepatitis\u2013epidemiology, pathophysiology and clinical management","volume":"122","author":"V Fuhrmann","year":"2010","journal-title":"Wiener Klinische Wochenschrift"},{"issue":"2","key":"pone.0230833.ref004","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0002-9343(00)00461-7","article-title":"Ischemic hepatitis: clinical presentation and pathogenesis","volume":"109","author":"RK Seeto","year":"2000","journal-title":"The American journal of medicine"},{"issue":"12","key":"pone.0230833.ref005","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.amjmed.2015.07.033","article-title":"The incidence and outcomes of ischemic hepatitis: a systematic review with meta-analysis","volume":"128","author":"EB Tapper","year":"2015","journal-title":"The American journal of medicine"},{"issue":"5","key":"pone.0230833.ref006","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1016\/j.nurpra.2017.02.013","article-title":"Ischemic Hepatitis: Risks for Sudden Liver Dysfunction","volume":"13","author":"MA Hall","year":"2017","journal-title":"The Journal for Nurse Practitioners"},{"issue":"3","key":"pone.0230833.ref007","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ijcard.2012.05.003","article-title":"Congestive hepatopathy and hypoxic hepatitis in heart failure: a cardiologist\u2019s point of view","volume":"166","author":"A Kavoliuniene","year":"2013","journal-title":"International journal of cardiology"},{"issue":"36","key":"pone.0230833.ref008","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1093\/eurheartj\/eht246","article-title":"Interactions of the heart and the liver","volume":"34","author":"S M\u00f8ller","year":"2013","journal-title":"European heart journal"},{"issue":"1","key":"pone.0230833.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2010.09.010","article-title":"Cardiovascular diseases and the liver","volume":"15","author":"IS Weisberg","year":"2011","journal-title":"Clinics in liver disease"},{"key":"pone.0230833.ref010","first-page":"1232","volume-title":"Mayo Clinic Proceedings","author":"EC Ebert","year":"2006"},{"issue":"4","key":"pone.0230833.ref011","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s12072-011-9336-1","article-title":"Hypoxic hepatitis: a challenging diagnosis","volume":"6","author":"G Trilok","year":"2012","journal-title":"Hepatology international"},{"issue":"3","key":"pone.0230833.ref012","first-page":"385","article-title":"Hypoxic hepatitis: a difficult diagnosis when the cardiomyopathy remains unrecognized and the course of liver enzymes follows an atypical pattern. 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