{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:55:27Z","timestamp":1793048127417,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T00:00:00Z","timestamp":1504828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031 6154"],"award-info":[{"award-number":["031 6154"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2018,2]]},"abstract":"Abstract<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n The analgesic flupirtine has been linked to cases of severe idiosyncratic drug\u2010induced liver injury (\n sFILI<\/jats:styled-content>\n ). We therefore examined whether N\u2010acetylcysteine (\n NAC<\/jats:styled-content>\n ) and glucocorticoid therapy is effective in the management of\n sFILI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In a retrospective cohort study efficacy of\n NAC<\/jats:styled-content>\n \u2010infusion and oral prednisolone treatments on liver\u2010function\u2010tests (\n LFT<\/jats:styled-content>\n s) and clinical outcome of 21\n sFILI<\/jats:styled-content>\n cases was evaluated by comparing it to an external cohort of 30\n sFILI<\/jats:styled-content>\n cases not receiving the antidote.\n LFT<\/jats:styled-content>\n s were also assayed in human hepatocyte cultures treated with flupirtine for 96\u00a0hours. Additionally, modulation of glutathione stores in cultures of human hepatocytes treated with 80 drugs was investigated.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Upon admission, patients presented Alanine aminotransferase (\n ALT<\/jats:styled-content>\n ), aspartate aminotransferase (\n AST<\/jats:styled-content>\n ) and bilirubin elevations of up to 90\u2010, 35\u2010 and 30\u2010fold of upper limits of normal (\n ULN<\/jats:styled-content>\n ) respectively. The average\n INR<\/jats:styled-content>\n was 2.2, and 50% of patients had a high Model for end\u2010stage liver disease (\n MELD<\/jats:styled-content>\n ) score of \u226525 and included 5 cases of 28\u201032. The combined\n NAC<\/jats:styled-content>\n \/prednisolone treatment was well tolerated and led to significant\n ALT<\/jats:styled-content>\n ,\n AST<\/jats:styled-content>\n and\n INR<\/jats:styled-content>\n improvements within 2\u00a0weeks. However, the hyperbilirubinaemia resolved slowly. Two patients with late start of\n NAC<\/jats:styled-content>\n \/prednisolone treatment developed hepatic encephalopathy and required liver transplantation; the remaining patients recovered without long\u2010term sequela. Based on serum biochemistries\n sFILI<\/jats:styled-content>\n cases resolved more rapidly (\n P<\/jats:italic>\n \u00a0<\u00a0.01) when compared to untreated\n sFILI<\/jats:styled-content>\n patients and included a case with fatal outcome. Additionally, in vitro studies revealed glutathione depletion as a common culprit for drugs with liver liabilities.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Based on these initial findings a prospective randomized clinical trial (RCT) is needed to confirm safety and efficacy of\n NAC<\/jats:styled-content>\n \/prednisolone treatment in\n sFILI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.13538","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T04:12:43Z","timestamp":1502079163000},"page":"365-376","source":"Crossref","is-referenced-by-count":26,"title":["N\u2010acetylcysteine and prednisolone treatment improved serum biochemistries in suspected flupirtine cases of severe idiosyncratic liver injury"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1558-9519","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Borlak","sequence":"first","affiliation":[{"name":"Centre for Pharmacology and Toxicology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"van B\u00f6mmel","sequence":"additional","affiliation":[{"name":"Section of Hepatology Clinic for Gastroenterology and Rheumatology University Hospital Leipzig Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berg","sequence":"additional","affiliation":[{"name":"Section of Hepatology Clinic for Gastroenterology and Rheumatology University Hospital Leipzig Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.032"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23588"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00111.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12522"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2014.09.010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.024364"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-011-1087-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2014.03.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2015.11.008"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(05)01028-1"},{"key":"e_1_2_9_13_1","first-page":"3143","article-title":"Glutathione synthesis","volume":"2013","author":"Lu SC","year":"1830","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.001"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.04.016"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28678"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.12.1499"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.6.4.341"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.06.006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-012-2512-x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2015.01.003"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025221"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.20113"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26678"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm493"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.13538","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.13538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T12:19:16Z","timestamp":1695471556000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.13538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,8]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/liv.13538"],"URL":"https:\/\/doi.org\/10.1111\/liv.13538","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,8]]}}}