{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T17:37:41Z","timestamp":1767980261044,"version":"3.49.0"},"reference-count":7,"publisher":"SMC Media","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Hepatic dysfunction, in the absence of liver metastases, occurs in 10\u201315% of renal cell carcinoma (RCC) patients, while immune hepatitis due to anti-CTLA4 and anti-PD1 administration affects about 3\u20139% and 0.7\u20131.8% of treated patients, respectively. Liver toxicity following combination therapy (anti-CTLA4 and anti-PD1) is seen in 29% of patients overall and grade 3\u20134 toxicity in 14% of patients. Stauffer\u2019s syndrome is a rare para-neoplastic phenomenon associated with RCC and characterized by abnormal liver function tests, hepato-splenomegaly and histological changes consistent with non-specific hepatitis. We describe a case of RCC treated with anti-CTLA4 and anti-PD1 therapy resulting in immediate liver toxicity and death after 2 months of progressive hepatic impairment. We hypothesize that high IL-6 levels due to Stauffer\u2019s syndrome might have contributed to immune-related hepatic failure.<\/jats:p>","DOI":"10.12890\/2021_002639","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T03:22:05Z","timestamp":1623900125000},"source":"Crossref","is-referenced-by-count":5,"title":["Unusual Fatal Outcome Following Administration of a Combination of anti-PD1 and anti-CTLA4 in Metastatic Renal Cell Carcinoma: Liver Toxicity Case Report and a Literature Review"],"prefix":"10.12890","volume":"8","author":[{"given":"Nerina","family":"Denaro","sequence":"additional","affiliation":[{"name":"Medical Oncology, St. Croce & Carle University Teaching Hospital, Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ornella","family":"Garrone","sequence":"additional","affiliation":[{"name":"Medical Oncology, St. Croce & Carle University Teaching Hospital, Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Occelli","sequence":"additional","affiliation":[{"name":"Medical Oncology, St. Croce & Carle University Teaching Hospital, Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Fea","sequence":"additional","affiliation":[{"name":"AO Santa Croce e Carle Cuneo"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Granetto","sequence":"additional","affiliation":[{"name":"Medical Oncology, St. Croce & Carle University Teaching Hospital, Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco Carlo","family":"Merlano","sequence":"additional","affiliation":[{"name":"edical Oncology, IRCCS Candiolo, Turin, Italy; ARCO Foundation, Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianmauro","family":"Numico","sequence":"additional","affiliation":[{"name":"Medical Oncology, St. Croce & Carle University Teaching Hospital, Cuneo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10397","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"10.12890\/2021_002639_ref1","doi-asserted-by":"crossref","unstructured":"li>Sznol M, Ferrucci PF, Hogg D, Atkins MB, Wolter P, Guidoboni M, et al. Pooled analysis safety profile of nivolumab and ipilimumab combination therapy in patients with advanced melanoma. <em>J Clin Oncol<\/em> 2017;<strong>35<\/strong>(34):3815\u20133822.<\/li>","DOI":"10.1200\/JCO.2016.72.1167"},{"key":"10.12890\/2021_002639_ref2","doi-asserted-by":"crossref","unstructured":"<li>Trinh S, Le A, Gowani S, La-Beck N. Management of immune-related adverse events associated with immune checkpoint inhibitor therapy: a minireview of current clinical guidelines. <em>Asia Pac J Oncol Nurs<\/em> 2019;<strong>6<\/strong>(2):154\u2013160.<\/li>","DOI":"10.4103\/apjon.apjon_3_19"},{"key":"10.12890\/2021_002639_ref3","doi-asserted-by":"crossref","unstructured":"<li>Brahmer JR, Lacchetti C, Thompson JA. 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