{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:30:39Z","timestamp":1783081839452,"version":"3.54.6"},"reference-count":38,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","pathologyjournal.rcpa.edu.au","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pathology"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1016\/j.pathol.2020.07.018","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T06:56:59Z","timestamp":1604300219000},"page":"220-228","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"title":["Electron microscopic observations in perfusion-fixed human non-alcoholic fatty liver disease biopsies"],"prefix":"10.1016","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-1124","authenticated-orcid":false,"given":"Pauline","family":"Verhaegh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Wisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toon","family":"de Munck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8202-7076","authenticated-orcid":false,"given":"Jan Willem","family":"Greve","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Verheij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Riedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Duimel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad","family":"Masclee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Jonkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger","family":"Koek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pathol.2020.07.018_bib1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease--Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000282080","article-title":"Epidemiology of non-alcoholic fatty liver disease","volume":"28","author":"Bellentani","year":"2010","journal-title":"Dig Dis"},{"key":"10.1016\/j.pathol.2020.07.018_bib3","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology","volume":"142","author":"Chalasani","year":"2012","journal-title":"Gastroenterology"},{"issue":"Suppl 4","key":"10.1016\/j.pathol.2020.07.018_bib4","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/jgh.12271","article-title":"Characteristics and diagnosis of NAFLD\/NASH","volume":"28","author":"Hashimoto","year":"2013","journal-title":"J\u00a0Gastroenterol Hepatol"},{"issue":"Suppl 1","key":"10.1016\/j.pathol.2020.07.018_bib5","first-page":"S17","article-title":"Pathophysiology of nonalcoholic steatohepatitis","volume":"40","author":"McCullough","year":"2006","journal-title":"J\u00a0Clin Gastroenterol"},{"key":"10.1016\/j.pathol.2020.07.018_bib6","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jhep.2008.06.018","article-title":"Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease","volume":"49","author":"Ong","year":"2008","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.pathol.2020.07.018_bib7","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat Med"},{"key":"10.1016\/j.pathol.2020.07.018_bib8","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1111\/hepr.12282","article-title":"Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease","volume":"44","author":"Fukuo","year":"2014","journal-title":"Hepatol Res"},{"key":"10.1016\/j.pathol.2020.07.018_bib9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.3109\/01913123.2013.799625","article-title":"What's in a name?-\"Lipolysosome\": ultrastructural features of a lipid-containing organelle","volume":"37","author":"Iancu","year":"2013","journal-title":"Ultrastruct Pathol"},{"key":"10.1016\/j.pathol.2020.07.018_bib10","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jhep.2010.04.031","article-title":"Hepatocellular ballooning in NASH","volume":"53","author":"Caldwell","year":"2010","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.pathol.2020.07.018_bib11","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1002\/hep.22851","article-title":"Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis","volume":"49","author":"Caldwell","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib12","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S0168-8278(99)80033-6","article-title":"Mitochondrial abnormalities in non-alcoholic steatohepatitis","volume":"31","author":"Caldwell","year":"1999","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.pathol.2020.07.018_bib13","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/j.1440-1746.2009.06142.x","article-title":"Electron microscopic findings in non-alcoholic fatty liver disease: is there a difference between hepatosteatosis and steatohepatitis?","volume":"25","author":"Ahishali","year":"2010","journal-title":"J\u00a0Gastroenterol Hepatol"},{"key":"10.1016\/j.pathol.2020.07.018_bib14","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.jhep.2019.02.012","article-title":"Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease","volume":"70","author":"Hammoutene","year":"2019","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.pathol.2020.07.018_bib15","doi-asserted-by":"crossref","first-page":"H1064","DOI":"10.1152\/ajpheart.00949.2015","article-title":"Dietary macronutrients and the aging liver sinusoidal endothelial cell","volume":"310","author":"Cogger","year":"2016","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.pathol.2020.07.018_bib16","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1530\/JME-14-0049","article-title":"oxLDL induces injury and defenestration of human liver sinusoidal endothelial cells via LOX1","volume":"53","author":"Zhang","year":"2014","journal-title":"J\u00a0Mol Endocrinol"},{"key":"10.1016\/j.pathol.2020.07.018_bib17","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1600-0676.1994.tb00080.x","article-title":"Endotoxin-induced defenestration of the hepatic sinusoidal endothelium: a factor in the pathogenesis of cirrhosis?","volume":"14","author":"Dobbs","year":"1994","journal-title":"Liver"},{"key":"10.1016\/j.pathol.2020.07.018_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0115005","article-title":"Formation of fenestrae in murine liver sinusoids depends on plasmalemma vesicle-associated protein and is required for lipoprotein passage","volume":"9","author":"Herrnberger","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.pathol.2020.07.018_bib19","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.3748\/wjg.v16.i23.2851","article-title":"Fixation methods for electron microscopy of human and other liver","volume":"16","author":"Wisse","year":"2010","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.pathol.2020.07.018_bib20","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/hep.26532","article-title":"Jet-fixation: a novel method to improve microscopy of human liver needle biopsies","volume":"59","author":"Vreuls","year":"2014","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib21","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/hep.25889","article-title":"Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients","volume":"56","author":"Bedossa","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib22","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1177\/019262339602400114","article-title":"Structure and function of sinusoidal lining cells in the liver","volume":"24","author":"Wisse","year":"1996","journal-title":"Toxicol Pathol"},{"key":"10.1016\/j.pathol.2020.07.018_bib23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0022-5320(70)90150-4","article-title":"An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids","volume":"31","author":"Wisse","year":"1970","journal-title":"J\u00a0Ultrastruct Res"},{"key":"10.1016\/j.pathol.2020.07.018_bib24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1097\/PAT.0b013e328351bcc8","article-title":"The liver sieve and atherosclerosis","volume":"44","author":"Fraser","year":"2012","journal-title":"Pathology"},{"key":"10.1016\/j.pathol.2020.07.018_bib25","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/apt.12046","article-title":"Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions?","volume":"36","author":"Yilmaz","year":"2012","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.pathol.2020.07.018_bib26","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/hep.23719","article-title":"Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites","volume":"52","author":"Neuschwander-Tetri","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib27","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00018-018-2947-0","article-title":"Molecular pathways of nonalcoholic fatty liver disease development and progression","volume":"76","author":"Bessone","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"10.1016\/j.pathol.2020.07.018_bib28","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/gt.2008.60","article-title":"The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer","volume":"15","author":"Wisse","year":"2008","journal-title":"Gene Ther"},{"key":"10.1016\/j.pathol.2020.07.018_bib29","first-page":"30","article-title":"Mistakes in mouse models of nonalcoholic steatophepatitis and how to avoid them","volume":"18","author":"Castro","year":"2018","journal-title":"UEG Educ"},{"key":"10.1016\/j.pathol.2020.07.018_bib30","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.jmbbm.2019.05.036","article-title":"Biomechanics of cultured hepatic cells during different steatogenic hits","volume":"97","author":"Baldini","year":"2019","journal-title":"J\u00a0Mech Behav Biomed Mater"},{"key":"10.1016\/j.pathol.2020.07.018_bib31","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1002\/hep.1840050427","article-title":"The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse","volume":"5","author":"Wisse","year":"1985","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib32","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/labinvest.2012.103","article-title":"Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture","volume":"92","author":"Francque","year":"2012","journal-title":"Lab Invest"},{"key":"10.1016\/j.pathol.2020.07.018_bib33","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1007\/s11695-018-03637-y","article-title":"Crashing NASH in patients listed for bariatric surgery","volume":"29","author":"De Munck","year":"2019","journal-title":"Obes Surg"},{"key":"10.1016\/j.pathol.2020.07.018_bib34","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.exger.2006.11.004","article-title":"Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid","volume":"42","author":"Jamieson","year":"2007","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.pathol.2020.07.018_bib35","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1053\/j.gastro.2005.03.084","article-title":"Sampling variability of liver biopsy in nonalcoholic fatty liver disease","volume":"128","author":"Ratziu","year":"2005","journal-title":"Gastroenterology"},{"key":"10.1016\/j.pathol.2020.07.018_bib36","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/hep.20202","article-title":"The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis","volume":"39","author":"Le","year":"2004","journal-title":"Hepatology"},{"key":"10.1016\/j.pathol.2020.07.018_bib37","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.3748\/wjg.v20.i15.4335","article-title":"Pediatric non-alcoholic steatohepatitis: the first report on the ultrastructure of hepatocyte mitochondria","volume":"20","author":"Lotowska","year":"2014","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.pathol.2020.07.018_bib38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/BF00218791","article-title":"Ultrastructural and biochemical studies of lipolysis by lipolysosomes in chick hepatocytes","volume":"255","author":"Kanai","year":"1989","journal-title":"Cell Tissue Res"}],"container-title":["Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0031302520309466?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0031302520309466?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T04:07:01Z","timestamp":1611374821000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0031302520309466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["S0031302520309466"],"URL":"https:\/\/doi.org\/10.1016\/j.pathol.2020.07.018","relation":{},"ISSN":["0031-3025"],"issn-type":[{"value":"0031-3025","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Electron microscopic observations in perfusion-fixed human non-alcoholic fatty liver disease biopsies","name":"articletitle","label":"Article Title"},{"value":"Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pathol.2020.07.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}