{"id":"https://openalex.org/W2414877618","doi":null,"title":"Histopathologic changes associated with fialuridine hepatotoxicity.","display_name":"Histopathologic changes associated with fialuridine hepatotoxicity.","publication_year":1997,"publication_date":"1997-03-01","ids":{"openalex":"https://openalex.org/W2414877618","mag":"2414877618","pmid":"https://pubmed.ncbi.nlm.nih.gov/9071726"},"language":"en","primary_location":{"id":"pmid:9071726","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/9071726","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","raw_type":"Journal Article"},"volume":null,"type":"article","indexed_in":["pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5019378601","display_name":"David Erwin Kleiner","orcid":"https://orcid.org/0000-0003-3442-4453","observed_orcids":["https://orcid.org/0000-0003-3442-4453"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"D E Kleiner","raw_affiliation_strings":["Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}]},{"author_position":"middle","author":{"id":null,"display_name":"M J Gaffey","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"M J Gaffey","raw_affiliation_strings":["UNIVERSITY OF VIRGINIA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"UNIVERSITY OF VIRGINIA;","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075848657","display_name":"Richard Sallie","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R Sallie","raw_affiliation_strings":["National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059497696","display_name":"Maria Tsokos","orcid":"https://orcid.org/0000-0001-8072-1358","observed_orcids":["https://orcid.org/0000-0001-8072-1358"]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"M Tsokos","raw_affiliation_strings":["National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5107808162","display_name":"Larry Nichols","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I170201317","display_name":"University of Pittsburgh","ror":"https://ror.org/01an3r305","country_code":"US","type":"education","lineage":["https://openalex.org/I170201317"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"L Nichols","raw_affiliation_strings":["Univ. of Pittsburgh"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Univ. of Pittsburgh","institution_ids":["https://openalex.org/I170201317"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110658519","display_name":"Robin McKenzie","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R McKenzie","raw_affiliation_strings":["National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111598177","display_name":"Stephen E. Straus","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"S E Straus","raw_affiliation_strings":["National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5112714557","display_name":"Jay H. Hoofnagle","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"J H Hoofnagle","raw_affiliation_strings":["National Institutes of Health"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"National Institutes of Health","institution_ids":["https://openalex.org/I1299303238"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":2.3434,"has_fulltext":false,"cited_by_count":68,"citation_normalized_percentile":{"value":0.88137666,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"10","issue":"3","first_page":"192","last_page":"9"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.9785000085830688,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.9785000085830688,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10340","display_name":"Hepatitis B Virus Studies","score":0.014800000004470348,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10151","display_name":"Hepatitis C virus research","score":0.0020000000949949026,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/fialuridine","display_name":"FIAU","score":0.9660000205039978},{"id":"https://openalex.org/keywords/hepatotoxicity","display_name":"hepatotoxicity","score":0.9459999799728394},{"id":"https://openalex.org/keywords/chronic-hepatitis-b","display_name":"chronic hepatitis B","score":0.9120000004768372},{"id":"https://openalex.org/keywords/nucleoside-analogs","display_name":"nucleoside analogues","score":0.8230000138282776},{"id":"https://openalex.org/keywords/antiviral-therapy","display_name":"antiviral therapy","score":0.6079999804496765},{"id":"https://openalex.org/keywords/microvesicular-steatosis","display_name":"microvesicular steatosis","score":0.8100000023841858},{"id":"https://openalex.org/keywords/bile-ductular-proliferation","display_name":"bile ductular proliferation","score":0.9570000171661377},{"id":"https://openalex.org/keywords/cholestasis","display_name":"cholestasis","score":0.9909999966621399},{"id":"https://openalex.org/keywords/mitochondrial-injury","display_name":"mitochondrial injury","score":0.8529999852180481},{"id":"https://openalex.org/keywords/liver-ultrastructure","display_name":"liver ultrastructure","score":0.6660000085830688},{"id":"https://openalex.org/keywords/lactic-acidosis","display_name":"lactic acidosis","score":0.7580000162124634},{"id":"https://openalex.org/keywords/pancreatitis","display_name":"pancreatitis","score":0.6700000166893005},{"id":"https://openalex.org/keywords/drug-induced-liver-injury","display_name":"drug-induced liver injury","score":0.6610000133514404}],"concepts":[{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.6722198724746704},{"id":"https://openalex.org/C2777071529","wikidata":"https://www.wikidata.org/wiki/Q12796879","display_name":"Mitochondrial toxicity","level":3,"score":0.6039162874221802},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5921365022659302},{"id":"https://openalex.org/C2778351090","wikidata":"https://www.wikidata.org/wiki/Q1349821","display_name":"Toxic hepatitis","level":3,"score":0.5914513468742371},{"id":"https://openalex.org/C2776175330","wikidata":"https://www.wikidata.org/wiki/Q1365091","display_name":"Steatosis","level":2,"score":0.5799815654754639},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.5442330241203308},{"id":"https://openalex.org/C2780317664","wikidata":"https://www.wikidata.org/wiki/Q1500373","display_name":"Lactic acidosis","level":2,"score":0.5369823575019836},{"id":"https://openalex.org/C2778019345","wikidata":"https://www.wikidata.org/wiki/Q1148337","display_name":"Hepatocellular carcinoma","level":2,"score":0.5149708390235901},{"id":"https://openalex.org/C2777766500","wikidata":"https://www.wikidata.org/wiki/Q360841","display_name":"Liver biopsy","level":3,"score":0.5010788440704346},{"id":"https://openalex.org/C90924648","wikidata":"https://www.wikidata.org/wiki/Q120569","display_name":"Gastroenterology","level":1,"score":0.4605414569377899},{"id":"https://openalex.org/C2775967933","wikidata":"https://www.wikidata.org/wiki/Q1527888","display_name":"Pancreatitis","level":2,"score":0.4427661597728729},{"id":"https://openalex.org/C2776029263","wikidata":"https://www.wikidata.org/wiki/Q131742","display_name":"Hepatitis","level":2,"score":0.3658236861228943},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.35408705472946167},{"id":"https://openalex.org/C2775934546","wikidata":"https://www.wikidata.org/wiki/Q179991","display_name":"Biopsy","level":2,"score":0.3417360782623291}],"mesh":[{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000998","descriptor_name":"Antiviral Agents","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D000998","descriptor_name":"Antiviral Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D001086","descriptor_name":"Arabinofuranosyluracil","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":false},{"descriptor_ui":"D001086","descriptor_name":"Arabinofuranosyluracil","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D001086","descriptor_name":"Arabinofuranosyluracil","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D002908","descriptor_name":"Chronic Disease","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006509","descriptor_name":"Hepatitis B","qualifier_ui":"Q000150","qualifier_name":"complications","is_major_topic":false},{"descriptor_ui":"D006509","descriptor_name":"Hepatitis B","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D006509","descriptor_name":"Hepatitis B","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016032","descriptor_name":"Randomized Controlled Trials as Topic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017322","descriptor_name":"Clinical Trials, Phase II as Topic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D056486","descriptor_name":"Chemical and Drug Induced Liver Injury","qualifier_ui":"Q000209","qualifier_name":"etiology","is_major_topic":false},{"descriptor_ui":"D056486","descriptor_name":"Chemical and Drug Induced Liver Injury","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true}],"locations_count":2,"locations":[{"id":"pmid:9071726","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/9071726","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc","raw_type":"Journal Article"},{"id":"mag:2414877618","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/9071726","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":"PubMed","raw_type":null}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2327070670","https://openalex.org/W2006154411","https://openalex.org/W2056909940","https://openalex.org/W2017775208","https://openalex.org/W4390823273","https://openalex.org/W2138201468","https://openalex.org/W7096840510","https://openalex.org/W2419346019","https://openalex.org/W2440864604","https://openalex.org/W7216969035"],"abstract_inverted_index":{"Chronic":[0],"hepatitis":[1,110,165],"B":[2,166],"is":[3,21],"a":[4,170],"widespread":[5],"viral":[6],"illness":[7],"with":[8,19,125,184,203,208],"the":[9,30,42,52,70,87,96,106,113,162,174,230],"serious":[10],"sequelae":[11],"of":[12,32,41,51,55,72,99,108,115,176,181,189,196,232],"cirrhosis":[13],"and":[14,25,65,79,83,102,137,145,193,198,211],"hepatocellular":[15,130],"carcinoma.":[16],"Current":[17],"therapy":[18],"interferon":[20],"not":[22,155],"universally":[23],"efficacious,":[24],"this":[26,92],"has":[27],"led":[28],"to":[29,94,103,112],"evaluation":[31],"other":[33,223],"antiviral":[34,224],"agents.":[35],"A":[36],"recent":[37],"Phase":[38],"II":[39],"trial":[40,93],"nucleoside":[43,225],"analogue,":[44],"fluoroiodoarabinofuranosyluracil":[45],"(fialuridine,":[46],"FIAU)":[47],"was":[48,121,169],"halted":[49],"because":[50],"sudden":[53],"development":[54],"severe":[56,152,209],"multisystem":[57],"toxicity":[58,101,153,205,233],"characterized":[59,122],"by":[60,123,161],"hepatic":[61,97,215],"failure,":[62],"lactic":[63],"acidosis,":[64],"pancreatitis,":[66],"which":[67,227],"resulted":[68],"in":[69,91,150,173,179,201],"deaths":[71],"five":[73],"patients.":[74],"We":[75],"systematically":[76],"evaluated":[77],"pre-":[78],"post-therapy":[80],"biopsy,":[81],"explant,":[82],"autopsy":[84],"specimens":[85],"from":[86,119],"15":[88],"patients":[89,183,202],"involved":[90],"define":[95],"changes":[98,159],"fialuridine":[100,120,204],"determine":[104],"whether":[105],"degree":[107],"pre-existing":[109],"contributed":[111],"severity":[114],"toxicity.":[116,190],"Severe":[117],"hepatotoxicity":[118],"hepatomegaly":[124],"diffuse,":[126],"predominantly":[127],"microvesicular":[128,177],"steatosis,":[129],"glycogen":[131],"depletion,":[132],"marked":[133,146],"bile":[134],"ductular":[135],"proliferation,":[136],"cholestasis.":[138],"Ultrastructural":[139],"examination":[140],"revealed":[141],"intracytoplasmic":[142],"lipid":[143],"droplets":[144],"mitochondrial":[147,210],"injury.":[148],"Patients":[149],"whom":[151],"did":[154],"develop":[156],"mainly":[157],"showed":[158],"caused":[160],"underlying":[163],"chronic":[164],"alone.":[167],"There":[168],"subtle":[171],"increase":[172],"amount":[175],"steatosis":[178],"two":[180],"six":[182],"mild":[185],"or":[186],"no":[187],"symptoms":[188,200],"The":[191],"microscopic":[192],"ultrastructural":[194],"pattern":[195],"injury":[197],"systemic":[199],"are":[206],"consistent":[207],"metabolic":[212],"derangements.":[213],"Similar":[214],"pathologic":[216],"findings":[217],"have":[218],"been":[219],"reported":[220],"rarely":[221],"for":[222],"analogues,":[226],"suggests":[228],"that":[229],"mechanisms":[231],"might":[234],"be":[235],"related.":[236]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":5},{"year":2017,"cited_by_count":6},{"year":2016,"cited_by_count":5},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":4},{"year":2012,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
