{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:11:43Z","timestamp":1773069103147,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["Bolyai Scholarship"],"award-info":[{"award-number":["Bolyai Scholarship"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and\/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three\u2010dimensional reconstruction of serial sections were applied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed \u03b1\u2010fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re\u2010establish the hepatic lobules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Regeneration of human livers following massive hepatic necrosis can occur in two ways\u2014either through proliferation of \u03b1\u2010fetoprotein\u2010positive acinary\u2010arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14721","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T01:58:54Z","timestamp":1557885534000},"page":"124-134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Human liver regeneration following massive hepatic necrosis: Two distinct patterns"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-0483","authenticated-orcid":false,"given":"Katalin","family":"Dezs\u0151","sequence":"first","affiliation":[{"name":"First Department of Pathology and Experimental Cancer Research Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-9221","authenticated-orcid":false,"given":"P\u00e9ter","family":"Nagy","sequence":"additional","affiliation":[{"name":"First Department of Pathology and Experimental Cancer Research Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-7729","authenticated-orcid":false,"given":"S\u00e1ndor","family":"Paku","sequence":"additional","affiliation":[{"name":"First Department of Pathology and Experimental Cancer Research Semmelweis University  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00178"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20562"},{"key":"e_1_2_5_4_1","first-page":"471","article-title":"The pathology of fatal epidemic hepatitis","volume":"20","author":"Luck\u00e9 B","year":"1944","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_5_1","first-page":"867","article-title":"The fulminant form of epidemic hepatitis","volume":"22","author":"Luck\u00e9 B","year":"1946","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_6_1","first-page":"70","article-title":"Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver","volume":"110","author":"Gerber MA","year":"1983","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_7_1","first-page":"397","article-title":"Morhometric and immunohistochemical characterization of human liver regeneration","volume":"147","author":"Rubin EM","year":"1995","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_8_1","first-page":"439","article-title":"Ductular reaction after submassive necrosis in humans. Special emphasis on analysis of ductular hepatocytes","volume":"149","author":"Demetris AJ","year":"1996","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230528"},{"key":"e_1_2_5_10_1","first-page":"348","article-title":"Characterization of ductular hepatocytes in primary liver allograft failure","volume":"10","author":"Fiel MI","year":"1997","journal-title":"Mod. Pathol."},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880029"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2006.01377.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-011-1115-9"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2012.07.018"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000092229.93203.57"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24080"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.3350\/kjhep.2010.16.3.334"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21665"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25713"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.11.014"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28661"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21172"},{"key":"e_1_2_5_23_1","first-page":"8910821","article-title":"Cellular mechanisms of liver regeneration and cell\u2010based therapies of liver diseases","author":"Kholodenko IV","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27706"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3203"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24122"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840120625"},{"key":"e_1_2_5_28_1","first-page":"289","article-title":"Distribution of \u03b1\u2010fetoprotein\u2010 and albumin\u2010containing cells in the livers of Fischer rats fed four cycles on N\u20102\u2010fluorenylacetamide in a choline\u2010deficient diet","volume":"114","author":"Sell S","year":"1984","journal-title":"Am. J. Pathol."},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.20886"},{"key":"e_1_2_5_30_1","first-page":"122","article-title":"Prognostic models for acute liver failure","volume":"9","author":"Du W","year":"2010","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03668.x"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840160604"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-007-0571-8"},{"key":"e_1_2_5_34_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/modpathol.2008.26","article-title":"Utility of glypican\u20103 in differentiating hepatocellular carcinoma from other primary and metastatic lesions in FNA of the liver: an immunocytochemical study","volume":"21","author":"Ligato S","journal-title":"Mod. Pathol."},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2018.01.003"},{"key":"e_1_2_5_36_1","first-page":"179","article-title":"The origin, hormonal nature, and action of hepatotrophic substances in portal venous blood","volume":"137","author":"Starzl TE","year":"1973","journal-title":"Surg. Gynecol. Obstet."},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049611"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711660407"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21568"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-2-27"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840210213"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.01.029"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s005350200099"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjgh.14721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.14721","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jgh.14721","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.14721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:02:51Z","timestamp":1694131371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.14721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,10]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/jgh.14721"],"URL":"https:\/\/doi.org\/10.1111\/jgh.14721","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,10]]},"assertion":[{"value":"2018-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}