{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:58:38Z","timestamp":1761541118869},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,1,20]],"date-time":"2013-01-20T00:00:00Z","timestamp":1358640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A clinically relevant, translational large animal model of acute liver failure (<jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>) is required for testing of novel therapies to prolong survival in acute liver failure, to permit spontaneous liver recovery or to act as a bridge to transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The aim was to establish a pig model of acetaminophen\u2010induced <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content> that mimics the human clinical syndrome, is managed as in a human intensive care unit and has a predictable survival time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nine female pigs were anaesthetised and instrumented for continuous intensive care monitoring and management using: target\u2010driven protocols for treatment of cardiovascular collapse, metabolic acidosis and electrolyte abnormalities; intermittent positive pressure ventilation; and continuous renal replacement therapy. Six animals were induced to <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content> with acetaminophen (paracetamol). Three animals acted as controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Irreversible acute liver failure, defined as rise in prothrombin time &gt;3 times normal, occurred 19.3\u00a0\u00b1\u00a01.8\u00a0h after the onset of acetaminophen administration. Death occurred predictably 12.6\u00a0\u00b1\u00a02.7\u00a0h thereafter, with acute hepatocellular necrosis in all animals. Clinical progression of liver failure mimicked the human condition including development of coagulopathy, intracranial hypertension, hyperammonaemia, cardiovascular collapse, elevation in creatinine, metabolic acidosis and hyperlactataemia. In addition, cardiovascular monitoring clearly demonstrated progressive cardiac dysfunction in <jats:styled-content style=\"fixed-case\">ALF<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A reproducible, clinically relevant, intensively managed, large animal model of acute liver failure, with death as a result of multi\u2010organ failure, has been successfully validated for translational studies of disease progression and therapies designed to prolong survival in man.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12042","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T08:17:03Z","timestamp":1352362623000},"page":"544-551","source":"Crossref","is-referenced-by-count":24,"title":["A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival"],"prefix":"10.1111","volume":"33","author":[{"given":"Karla C. L.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences Royal Veterinary College University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Palacios Jimenez","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Royal Veterinary College University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatim","family":"Alibhai","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Royal Veterinary College University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Mei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Royal Veterinary College University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela J.","family":"Leckie","sequence":"additional","affiliation":[{"name":"Liver Failure Group Institute of Liver and Digestive Health University College London Medical School Royal Free Campus London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Royal Veterinary College University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Stanzani","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Royal Veterinary College University of London  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"L. 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