{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:58:03Z","timestamp":1776128283901,"version":"3.50.1"},"reference-count":31,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","dldjournalonline.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Digestive and Liver Disease"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1016\/j.dld.2019.06.017","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T07:50:36Z","timestamp":1562572236000},"page":"1074-1078","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":39,"title":["Hepatotoxicity of immune check point inhibitors: Approach and management"],"prefix":"10.1016","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0561-7902","authenticated-orcid":false,"given":"Ana","family":"Lleo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-3615","authenticated-orcid":false,"given":"Lorenza","family":"Rimassa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.dld.2019.06.017_bib0005","doi-asserted-by":"crossref","first-page":"261","DOI":"10.21037\/atm.2016.04.01","article-title":"Harnessing the immune system to improve cancer therapy","volume":"4","author":"Papaioannou","year":"2016","journal-title":"Ann Transl Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0010","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrd.2015.35","article-title":"Development of immuno-oncology drugs \u2014 from CTLA4 to PD1 to the next generations","volume":"15","author":"Hoos","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.dld.2019.06.017_bib0015","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N Engl J Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0020","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in previously untreated melanoma without BRAF mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0025","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S0140-6736(14)60958-2","article-title":"Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial","volume":"384","author":"Robert","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.dld.2019.06.017_bib0030","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0035","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0040","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.dld.2019.06.017_bib0045","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1056\/NEJMoa1414428","article-title":"Nivolumab and ipilimumab versus ipilimumab in untreated melanoma","volume":"372","author":"Postow","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0050","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0055","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/ni.2691","article-title":"Immune surveillance by the liver","volume":"14","author":"Jenne","year":"2013","journal-title":"Nat Immunol"},{"key":"10.1016\/j.dld.2019.06.017_bib0060","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13045-018-0582-8","article-title":"Next generation of immune checkpoint therapy in cancer: new developments and challenges","volume":"11","author":"Marin-Acevedo","year":"2018","journal-title":"J Hematol Oncol"},{"key":"10.1016\/j.dld.2019.06.017_bib0065","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13045-017-0552-6","article-title":"Cancer immunotherapy beyond immune checkpoint inhibitors","volume":"11","author":"Marin-Acevedo","year":"2018","journal-title":"J Hematol Oncol"},{"key":"10.1016\/j.dld.2019.06.017_bib0070","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1053\/j.gastro.2017.06.007","article-title":"Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features","volume":"153","author":"Sia","year":"2017","journal-title":"Gastroenterology"},{"key":"10.1016\/j.dld.2019.06.017_bib0075","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.bulcan.2018.07.005","article-title":"Physiopathological mechanisms of immune-related adverse events induced by anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies in cancer treatment","volume":"105","author":"Passat","year":"2018","journal-title":"Bull Cancer"},{"key":"10.1016\/j.dld.2019.06.017_bib0080","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12916-015-0455-8","article-title":"Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis","volume":"13","author":"Bertrand","year":"2015","journal-title":"BMC Med"},{"key":"10.1016\/j.dld.2019.06.017_bib0085","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3389\/fonc.2017.00056","article-title":"Incidence of immune-related adverse events with program death Receptor-1- and program death Receptor-1 ligand-directed therapies in genitourinary cancers","volume":"7","author":"Maughan","year":"2017","journal-title":"Front Oncol"},{"key":"10.1016\/j.dld.2019.06.017_bib0090","first-page":"560","article-title":"Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities","volume":"4","author":"Villadolid","year":"2015","journal-title":"Transl Lung Cancer Res"},{"key":"10.1016\/j.dld.2019.06.017_bib0095","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s40425-017-0300-z","article-title":"Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group","volume":"5","author":"Puzanov","year":"2017","journal-title":"J Immunother Cancer"},{"key":"10.1016\/j.dld.2019.06.017_bib0100","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1634\/theoncologist.2014-0422","article-title":"The evolving role of immune checkpoint inhibitors in Cancer treatment","volume":"20","author":"Pennock","year":"2015","journal-title":"Oncologist"},{"key":"10.1016\/j.dld.2019.06.017_bib0105","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.18632\/oncotarget.2980","article-title":"PD-1 pathway inhibitors: the next generation of immunotherapy for advanced melanoma","volume":"6","author":"Luke","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.dld.2019.06.017_bib0110","unstructured":"https:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/CTCAE_4.03\/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf."},{"key":"10.1016\/j.dld.2019.06.017_bib0115","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.dld.2019.06.017_bib0120","doi-asserted-by":"crossref","DOI":"10.1016\/S0168-8278(18)30249-6","article-title":"Hepatic safety and biomarker assessments in sorafenib experienced patients with advanced hepatocellular carcinoma treated with nivolumab in the CheckMate-040 study","volume":"68","author":"Meyer","year":"2018","journal-title":"J Hepatol"},{"key":"10.1016\/j.dld.2019.06.017_bib0125","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/ijc.30678","article-title":"Risk of hepatotoxicity in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis of published data","volume":"141","author":"Wang","year":"2017","journal-title":"Int J Cancer"},{"key":"10.1016\/j.dld.2019.06.017_bib0130","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.jhep.2018.01.033","article-title":"Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors","volume":"68","author":"De Martin","year":"2018","journal-title":"J Hepatol"},{"key":"10.1016\/j.dld.2019.06.017_bib0135","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1002\/hep.30157","article-title":"Nodular regenerative hyperplasia associated with immune checkpoint blockade","volume":"68","author":"LoPiccolo","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.dld.2019.06.017_bib0140","unstructured":"https:\/\/www.fda.gov\/Drugs\/default.htm."},{"issue":"6","key":"10.1016\/j.dld.2019.06.017_bib0145","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.jhep.2019.02.014","article-title":"EASL clinical practice guidelines: drug-induced liver injury","volume":"70","author":"European Association for the Study of the Liver","year":"2019","journal-title":"J Hepatol"},{"key":"10.1016\/j.dld.2019.06.017_bib0150","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejca.2015.11.016","article-title":"Immune-related adverse events with immune checkpoint blockade: a comprehensive review","volume":"54","author":"Michot","year":"2016","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.dld.2019.06.017_bib0155","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1111\/liv.13746","article-title":"Hepatotoxicity of immune checkpoint inhibitors: an evolving picture of risk associated with a vital class of immunotherapy agents","volume":"38","author":"Suzman","year":"2018","journal-title":"Liver Int"}],"container-title":["Digestive and Liver Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1590865819306747?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1590865819306747?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T04:09:39Z","timestamp":1761624579000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1590865819306747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["S1590865819306747"],"URL":"https:\/\/doi.org\/10.1016\/j.dld.2019.06.017","relation":{},"ISSN":["1590-8658"],"issn-type":[{"value":"1590-8658","type":"print"}],"subject":[],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepatotoxicity of immune check point inhibitors: Approach and management","name":"articletitle","label":"Article Title"},{"value":"Digestive and Liver Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.dld.2019.06.017","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"https:\/\/doi.org\/10.1016\/j.dld.2019.05.006","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}