{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:44:35Z","timestamp":1789757075651,"version":"4.0.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4230,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The murine model of hereditary tyrosinemia type 1 (HT1) was used to analyze the relationship between chronic liver disease and programmed cell death <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. In healthy fumarylacetoacetate hydrolase deficient mice (<jats:italic toggle=\"yes\">Fah<\/jats:italic>\n                                 <jats:sup>-\/-<\/jats:sup>), protected from liver injury by the drug 2-(2- nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), the tyrosine metabolite homogentisic acid (HGA) caused rapid hepatocyte death. In contrast, all mice survived the same otherwise lethal dose of HGA if they had preexisting liver damage induced by NTBC withdrawal. Similarly, <jats:italic toggle=\"yes\">Fah<\/jats:italic>\n                                 <jats:sup>-\/-<\/jats:sup> animals with liver injury were also resistant to apoptosis induced by the Fas ligand Jo-2 and to necrosis-like cell death induced by acetaminophen (APAP). Molecular studies revealed a marked up-regulation of the antiapoptotic heat shock proteins (Hsp) 27, 32, and 70 and of c-Jun in hepatocytes of stressed mice. In addition, the p38 and Jun N-terminal kinase (JNK) stress-activated kinase pathways were markedly impaired in the cell-death resistant liver. In conclusion, these results provide evidence that chronic liver disease can paradoxically result in cell death resistance <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. Stress-induced failure of cell death programs may lead to an accumulation of damaged cells and therefore enhance the risk for cancer as observed in HT1 and other chronic liver diseases. (Hepatology 2004;39:433-443.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20077","type":"journal-article","created":{"date-parts":[[2004,2,3]],"date-time":"2004-02-03T17:05:53Z","timestamp":1075827953000},"page":"433-443","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":61,"title":["Chronic liver disease in murine hereditary tyrosinemia type 1 induces resistance to cell death"],"prefix":"10.1097","volume":"39","author":[{"given":"Arndt","family":"Vogel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge E.T.","family":"van den 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