{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:22:32Z","timestamp":1792725752723,"version":"4.5.0"},"reference-count":80,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, has been a paradigm shift in cancer therapeutics, producing durable cancer responses across a range of primary malignancies. ICI drugs increase immune activity against tumor cells, but may also reduce immune tolerance to self-antigens, resulting in immune-mediated tissue damage. ICI-associated hepatotoxicity usually manifests as hepatocellular enzyme elevation and may occur in 2%\u201325% of ICI-treated patients. Although ICI-associated hepatotoxicity is clinically and pathologically distinct from idiopathic autoimmune hepatitis, our understanding of its pathogenesis continues to evolve. Pending greater understanding of the pathophysiology, mainstay of management remains through treatment with high-dose corticosteroids. This approach works for many patients, but up to 30% of patients with high-grade hepatotoxicity may not respond to corticosteroids alone. Furthermore, atypical cholestatic presentations are increasingly recognized, and rare cases of fulminant hepatitis due to ICI hepatotoxicity have been reported. Optimal management for these challenging patients remains uncertain. Herein, we review the current understanding of pathogenesis of ICI-associated toxicities, with a focus on hepatotoxicity. Based on the existing literature, we propose evolving management approaches to incorporate strategies to limit excess corticosteroid exposure, and address rare but important presentations of cholestatic hepatitis and fulminant liver failure. Finally, as ICI hepatotoxicity frequently occurs in the context of treatment for advanced malignancy, we review the impact of hepatotoxicity and its treatment on cancer outcomes, and the overall safety of re-challenge with ICI, for patients who may have limited treatment options.<\/jats:p>","DOI":"10.1097\/hep.0000000000000045","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T08:00:31Z","timestamp":1673510431000},"page":"198-212","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":72,"title":["Checkpoint inhibitor hepatotoxicity: pathogenesis and management"],"prefix":"10.1097","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-9523","authenticated-orcid":false,"given":"Morven","family":"Cunningham","sequence":"first","affiliation":[{"name":"Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5195-4443","authenticated-orcid":false,"given":"Rohit","family":"Gupta","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-7057","authenticated-orcid":false,"given":"Marcus","family":"Butler","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"R1-20250818","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/j.cell.2021.02.011","article-title":"Understanding and treating the inflammatory adverse events of cancer immunotherapy","volume":"184","author":"Dougan","year":"2021","journal-title":"Cell"},{"key":"R2-20250818","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"R3-20250818","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"},{"issue":"suppl 4","key":"R4-20250818","doi-asserted-by":"crossref","first-page":"iv119","DOI":"10.1093\/annonc\/mdx225","article-title":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Haanen","year":"2017","journal-title":"Ann Oncol"},{"key":"R5-20250818","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3389\/fimmu.2019.00167","article-title":"Regulation of monocyte-macrophage responses in cirrhosis-role of innate immune programming and checkpoint receptors","volume":"10","author":"Riva","year":"2019","journal-title":"Front Immunol"},{"key":"R6-20250818","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.immuni.2013.07.005","article-title":"Deciphering and reversing tumor immune suppression","volume":"39","author":"Motz","year":"2013","journal-title":"Immunity"},{"key":"R7-20250818","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.it.2019.04.002","article-title":"Adverse events following cancer immunotherapy: obstacles and opportunities","volume":"40","author":"Pauken","year":"2019","journal-title":"Trends Immunol"},{"key":"R8-20250818","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":"R9-20250818","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000500902","article-title":"On the horizon: targeting next-generation immune checkpoints for cancer treatment","volume":"64","author":"Tundo","year":"2019","journal-title":"Chemotherapy"},{"key":"R10-20250818","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N Engl J Med"},{"key":"R11-20250818","first-page":"125","article-title":"Advances in cancer immunology and cancer immunotherapy","volume":"21","author":"Voena","year":"2016","journal-title":"Discov Med"},{"key":"R12-20250818","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1016\/j.apsb.2021.10.003","article-title":"Mechanisms of immune checkpoint inhibitor-mediated liver injury","volume":"11","author":"Shojaie","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"R13-20250818","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nri724","article-title":"Epitope spreading in immune-mediated diseases: implications for immunotherapy","volume":"2","author":"Vanderlugt","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"R14-20250818","doi-asserted-by":"crossref","first-page":"108377","DOI":"10.1016\/j.clim.2020.108377","article-title":"Immune-related adverse events of checkpoint inhibitors: Insights into immunological dysregulation","volume":"213","author":"Yang","year":"2020","journal-title":"Clin Immunol"},{"key":"R15-20250818","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1158\/0008-5472.CAN-16-2324","article-title":"Immune toxicities elicted by CTLA-4 blockade in cancer patients are associated with early diversification of the T-cell repertoire","volume":"77","author":"Oh","year":"2017","journal-title":"Cancer Res"},{"key":"R16-20250818","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1001\/jamaoncol.2019.0402","article-title":"Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in non-small cell lung cancer","volume":"5","author":"Berner","year":"2019","journal-title":"JAMA Oncol"},{"key":"R17-20250818","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.cell.2017.07.024","article-title":"Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade","volume":"170","author":"Wei","year":"2017","journal-title":"Cell"},{"key":"R18-20250818","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41416-018-0155-1","article-title":"Immune dysregulation in cancer patients developing immune-related adverse events","volume":"120","author":"Khan","year":"2019","journal-title":"Br J Cancer"},{"key":"R19-20250818","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.semcancer.2019.01.006","article-title":"Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis","volume":"64","author":"Kumar","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"R20-20250818","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1158\/2326-6066.CIR-20-0969","article-title":"Regulatory T-cell transcriptomic reprogramming characterizes adverse events by checkpoint inhibitors in solid tumors","volume":"9","author":"Grigoriou","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"R21-20250818","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":"R22-20250818","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1097\/PAS.0000000000000453","article-title":"Ipilimumab-associated hepatitis: clinicopathologic characterization in a series of 11 cases","volume":"39","author":"Johncilla","year":"2015","journal-title":"Am J Surg Pathol"},{"key":"R23-20250818","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":"R24-20250818","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1080\/25785826.2020.1788229","article-title":"Fatal fulminant hepatitis induced by combined ipilimumab and nivolumab therapy despite favorable histologic response and confirmed by autopsy in a patient with clear cell renal cell carcinoma","volume":"44","author":"Kubo","year":"2021","journal-title":"Immunol Med"},{"key":"R25-20250818","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jhep.2021.02.008","article-title":"Activation and transcriptional profile of monocytes and CD8","volume":"75","author":"Gudd","year":"2021","journal-title":"J Hepatol"},{"key":"R26-20250818","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/14737140.2022.2094772","article-title":"Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer","volume":"22","author":"Issa","year":"2022","journal-title":"Expert Rev Anticancer Ther"},{"key":"R27-20250818","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s00262-020-02797-0","article-title":"Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors","volume":"70","author":"Abdel-Wahab","year":"2021","journal-title":"Cancer Immunol Immunother"},{"key":"R28-20250818","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"},{"key":"R29-20250818","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s12072-021-10151-4","article-title":"Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients","volume":"15","author":"Biewenga","year":"2021","journal-title":"Hepatol Int"},{"key":"R30-20250818","doi-asserted-by":"crossref","first-page":"e0253070","DOI":"10.1371\/journal.pone.0253070","article-title":"Evaluation of liver enzyme elevations and hepatotoxicity in patients treated with checkpoint inhibitor immunotherapy","volume":"16","author":"Cunningham","year":"2021","journal-title":"PLoS One"},{"key":"R31-20250818","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1097\/COC.0000000000000374","article-title":"Hepatotoxicity after immune checkpoint inhibitor therapy in melanoma: natural progression and management","volume":"41","author":"Huffman","year":"2018","journal-title":"Am J Clin Oncol"},{"key":"R32-20250818","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jamaoncol.2019.0393","article-title":"Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis","volume":"5","author":"Wang","year":"2019","journal-title":"JAMA Oncol"},{"key":"R33-20250818","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1093\/annonc\/mdx286","article-title":"Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review","volume":"28","author":"Khoja","year":"2017","journal-title":"Ann Oncol"},{"key":"R34-20250818","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/ijc.32132","article-title":"A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors","volume":"145","author":"Arnaud-Coffin","year":"2019","journal-title":"Int J Cancer"},{"key":"R35-20250818","doi-asserted-by":"crossref","first-page":"570752","DOI":"10.3389\/fonc.2020.570752","article-title":"Incidence of skin and respiratory immune-related adverse events correlates with specific tumor types in patients treated with checkpoint inhibitors","volume":"10","author":"Rose","year":"2020","journal-title":"Front Oncol"},{"key":"R36-20250818","doi-asserted-by":"crossref","first-page":"650292","DOI":"10.3389\/fonc.2021.650292","article-title":"Immune checkpoint inhibitor associated hepatotoxicity in primary liver cancer versus other cancers: a systematic review and meta-analysis","volume":"11","author":"Fu","year":"2021","journal-title":"Front Oncol"},{"key":"R37-20250818","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N Engl J Med"},{"key":"R38-20250818","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.critrevonc.2019.06.004","article-title":"The microbiome and cancer for clinicians","volume":"141","author":"Picardo","year":"2019","journal-title":"Crit Rev Oncol Hematol"},{"key":"R39-20250818","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1093\/annonc\/mdx108","article-title":"Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab","volume":"28","author":"Chaput","year":"2017","journal-title":"Ann Oncol"},{"key":"R40-20250818","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/s41591-021-01406-6","article-title":"Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade","volume":"27","author":"Andrews","year":"2021","journal-title":"Nat Med"},{"key":"R41-20250818","doi-asserted-by":"crossref","first-page":"10391","DOI":"10.1038\/ncomms10391","article-title":"Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis","volume":"7","author":"Dubin","year":"2016","journal-title":"Nat Commun"},{"key":"R42-20250818","doi-asserted-by":"crossref","first-page":"e000268","DOI":"10.1136\/esmoopen-2017-000268","article-title":"Severe steroid-resistant anti-PD1 T-cell checkpoint inhibitor-induced hepatotoxicity driven by biliary injury","volume":"2","author":"Doherty","year":"2017","journal-title":"ESMO Open"},{"key":"R43-20250818","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1056\/NEJMra1816149","article-title":"Drug-induced liver injury\u2014types and phenotypes","volume":"381","author":"Hoofnagle","year":"2019","journal-title":"N Engl J Med"},{"key":"R44-20250818","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/apt.15413","article-title":"Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy","volume":"50","author":"Tsung","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"R45-20250818","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1111\/liv.14489","article-title":"Immune-related hepatitis related to checkpoint inhibitors: clinical and prognostic factors","volume":"40","author":"Riveiro-Barciela","year":"2020","journal-title":"Liver Int"},{"key":"R46-20250818","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/j.1365-2036.2010.04370.x","article-title":"Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection","volume":"32","author":"Alazawi","year":"2010","journal-title":"Aliment Pharmacol Ther"},{"key":"R47-20250818","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1634\/theoncologist.2018-0174","article-title":"Diagnosis and management of hepatitis in patients on checkpoint blockade","volume":"23","author":"Reynolds","year":"2018","journal-title":"Oncologist"},{"key":"R48-20250818","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41379-020-00653-1","article-title":"Liver biopsy findings in patients on immune checkpoint inhibitors","volume":"34","author":"Cohen","year":"2021","journal-title":"Mod Pathol"},{"key":"R49-20250818","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1001\/jamaoncol.2021.4342","article-title":"Utility of liver biopsy in diagnosis and management of high-grade immune checkpoint inhibitor hepatitis in patients with cancer","volume":"7","author":"Li","year":"2021","journal-title":"JAMA Oncol"},{"key":"R51-20250818","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2165\/00002018-200932010-00005","article-title":"Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct","volume":"32","author":"Fontana","year":"2009","journal-title":"Drug Saf"},{"key":"R52-20250818","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/clpt.2011.58","article-title":"Case definition and phenotype standardization in drug-induced liver injury","volume":"89","author":"Aithal","year":"2011","journal-title":"Clin Pharmacol Ther"},{"key":"R53-20250818","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.jtho.2021.06.024","article-title":"Beyond steroids: immunosuppressants in steroid-refractory or resistant immune-related adverse events","volume":"16","author":"Luo","year":"2021","journal-title":"J Thorac Oncol"},{"key":"R54-20250818","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.jhep.2018.03.034","article-title":"Immune-related hepatitis with immunotherapy: are corticosteroids always needed?","volume":"69","author":"Gauci","year":"2018","journal-title":"J Hepatol"},{"key":"R55-20250818","doi-asserted-by":"crossref","first-page":"251","DOI":"10.14309\/ajg.0000000000000398","article-title":"Clinical characteristics and adverse impact of hepatotoxicity due to immune checkpoint inhibitors","volume":"115","author":"Miller","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"R56-20250818","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/hep.32215","article-title":"Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis","volume":"75","author":"Li","year":"2022","journal-title":"Hepatology"},{"key":"R57-20250818","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1136\/flgastro-2018-101146","article-title":"Immunotherapy-related hepatitis: real-world experience from a tertiary centre","volume":"10","author":"Cheung","year":"2019","journal-title":"Frontline Gastroenterol"},{"key":"R58-20250818","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1684\/ejd.2017.2973","article-title":"Azathioprine combination therapy for steroid-refractory hepatic immune system-related adverse events","volume":"27","author":"Iwamoto","year":"2017","journal-title":"Eur J Dermatol"},{"key":"R62-20250818","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.3390\/curroncol28030201","article-title":"Real world outcomes and hepatotoxicity of infliximab in the treatment of steroid-refractory immune-related adverse events","volume":"28","author":"Araujo","year":"2021","journal-title":"Curr Oncol"},{"key":"R63-20250818","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.ejca.2019.04.022","article-title":"Three cases of immune cholangitis related to anti-programmed cell death and programmed cell death ligand agents for the treatment of non-small cell lung cancer","volume":"115","author":"Fouchard","year":"2019","journal-title":"Eur J Cancer"},{"key":"R64-20250818","article-title":"Immune checkpoint inhibitor-related cholangiopathy: novel clinicopathological description of a multi-centre cohort","author":"Berry","year":"2022","journal-title":"Liver Int"},{"key":"R65-20250818","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1159\/000507695","article-title":"Fatal cholestatic liver injury during treatment with PD1 immune checkpoint inhibitor for malignant melanoma: a case report","volume":"13","author":"Thorsteinsdottir","year":"2020","journal-title":"Case Rep Oncol"},{"key":"R66-20250818","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1002\/hep.28967","article-title":"Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements","volume":"65","author":"Bonkovsky","year":"2017","journal-title":"Hepatology"},{"key":"R67-20250818","doi-asserted-by":"crossref","first-page":"583781","DOI":"10.3389\/fonc.2020.583781","article-title":"Case report: lymphocytosis associated with fatal hepatitis in a thymoma patient treated with anti-PD1: new insight into the immune-related storm","volume":"10","author":"Argentiero","year":"2020","journal-title":"Front Oncol"},{"key":"R68-20250818","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jhep.2018.10.020","article-title":"Acute liver failure due to immune-mediated hepatitis successfully managed with plasma exchange: new settings call for new treatment strategies?","volume":"70","author":"Riveiro-Barciela","year":"2019","journal-title":"J Hepatol"},{"key":"R69-20250818","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.jhep.2018.06.012","article-title":"Mortality due to immunotherapy related hepatitis","volume":"69","author":"Bhave","year":"2018","journal-title":"J Hepatol"},{"key":"R70-20250818","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1002\/hep.31396","article-title":"Severe refractory checkpoint inhibitor-related hepatitis reversed with anti-thymocyte globulin and n-acetylcysteine","volume":"72","author":"Motomura","year":"2020","journal-title":"Hepatology"},{"key":"R71-20250818","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00262-017-2107-7","article-title":"Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report","volume":"67","author":"McGuire","year":"2018","journal-title":"Cancer Immunol Immunother"},{"key":"R72-20250818","first-page":"5908411","article-title":"Plasmapheresis for pembrolizumab-induced hepatitis in a patient with squamous cell carcinoma and prior orthotopic liver transplantation","volume":"2022","author":"Al-Nattah","year":"2022","journal-title":"Case Rep Hepatol"},{"key":"R73-20250818","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s40425-019-0805-8","article-title":"Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors","volume":"7","author":"Das","year":"2019","journal-title":"J Immunother Cancer"},{"key":"R74-20250818","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1158\/1078-0432.CCR-15-1136","article-title":"Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes","volume":"22","author":"Freeman-Keller","year":"2016","journal-title":"Clin Cancer Res"},{"key":"R75-20250818","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1200\/JCO.2015.66.1389","article-title":"Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma","volume":"35","author":"Weber","year":"2017","journal-title":"J Clin Oncol"},{"key":"R76-20250818","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1001\/jamaoncol.2019.5570","article-title":"Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive pembrolizumab or placebo: a secondary analysis of a randomized clinical trial","volume":"6","author":"Eggermont","year":"2020","journal-title":"JAMA Oncol"},{"key":"R77-20250818","doi-asserted-by":"crossref","first-page":"e002535","DOI":"10.1136\/jitc-2021-002535","article-title":"Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis","volume":"9","author":"Tarhini","year":"2021","journal-title":"J Immunother Cancer"},{"key":"R78-20250818","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1002\/cncr.31629","article-title":"High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma","volume":"124","author":"Faje","year":"2018","journal-title":"Cancer"},{"key":"R79-20250818","doi-asserted-by":"crossref","first-page":"5088","DOI":"10.1002\/cncr.33165","article-title":"Outcomes after resumption of immune checkpoint inhibitor therapy after high-grade immune-mediated hepatitis","volume":"126","author":"Li","year":"2020","journal-title":"Cancer"},{"key":"R80-20250818","article-title":"Retreatment with checkpoint inhibitors after a severe immune-related hepatitis: results from a prospective multicenter study","author":"Riveiro-Barciela","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"R81-20250818","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.jhep.2016.11.015","article-title":"Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids","volume":"66","author":"Ziemer","year":"2017","journal-title":"J Hepatol"},{"key":"R82-20250818","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1001\/jamaoncol.2020.0726","article-title":"Immune checkpoint inhibitor rechallenge after immune-related adverse events in patients with cancer","volume":"6","author":"Dolladille","year":"2020","journal-title":"JAMA Oncol"},{"key":"R83-20250818","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/annonc\/mdx642","article-title":"Safety of resuming anti-PD-1 in patients with immune-related adverse events (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma","volume":"29","author":"Pollack","year":"2018","journal-title":"Ann Oncol"},{"key":"R84-20250818","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/annonc\/mdw443","article-title":"Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab","volume":"28","author":"Menzies","year":"2017","journal-title":"Ann Oncol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/HEP.0000000000000045","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:02:39Z","timestamp":1755561759000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/HEP.0000000000000045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,13]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.1097\/hep.0000000000000045","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1,13]]},"assertion":[{"value":"2022-08-01","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-08","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}