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It can have several underlying causes. Despite its prevalence in critically ill patients, which can reach upwards of 10%, very little is known about the mechanisms of injury. Thus, we set out to measure previously identified circulating biomarkers in an attempt to describe mechanisms of injury following hypoxic hepatitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma from patients diagnosed with hypoxic hepatitis was collected for this study. Biomarkers of hepatocellular injury, mitochondrial damage and cell death were measured. These results were compared against results obtained from well\u2010characterized acetaminophen overdose patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At peak injury, <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> measured 4082\u00b1606\u00a0U\/L and gradually decreased over 5\u00a0days, corresponding to the clinically observed pattern of hypoxic hepatitis. Levels of <jats:styled-content style=\"fixed-case\">GDH<\/jats:styled-content> showed a similar pattern, but neither <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> nor <jats:styled-content style=\"fixed-case\">GDH<\/jats:styled-content> were significantly higher in these patients than in acetaminophen patients. Plasma levels of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragments mimicked hepatocellular injury as measured by <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> and mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010122. Interestingly, we found a significant increase in caspase\u2010cleaved cytokeratin\u201018; however, the full\u2010length form greatly exceeded the cleaved form at the time of maximum injury (45837\u00b112085 vs 2528\u00b11074\u00a0U\/L). We also found an increase in ac<jats:styled-content style=\"fixed-case\">HMGB<\/jats:styled-content>1 at later time points indicating a possible role of inflammation, but cytokine levels at these times were actually decreased relative to early time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The mechanism of injury following hypoxic hepatitis involves mitochondrial damage and <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> fragmentation. Importantly, necrosis, rather than apoptosis, is the main mode of cell death.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13202","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T14:42:38Z","timestamp":1468852958000},"page":"377-384","source":"Crossref","is-referenced-by-count":36,"title":["Plasma biomarkers to study mechanisms of liver injury in patients with hypoxic hepatitis"],"prefix":"10.1111","volume":"37","author":[{"given":"James L.","family":"Weemhoff","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Therapeutics University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin L.","family":"Woolbright","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Therapeutics University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalind 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