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. 2021 Mar 4;12:1439. doi: 10.1038/s41467-021-21572-y

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© The Author(s) 2021, corrected publication 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Individualised treatment of melanoma is guided by tumour staging, presence of B-RAF mutations and fitness-for-toxicity. b Colitis, hepatitis and thyroiditis are common immune-related complications of dual therapy with Nivolumab plus Ipilimumab; 31.4% of patients experienced two or more of these immune-related adverse reactions (n = 89). c Colitis, hepatitis and thyroiditis occurred independently and were not significantly associated with clinical response (n = 89; F.E). d–h Patients who developed hepatitis of any grade following dual therapy lacked biochemical signs of liver inflammation before treatment. In particular, no clinically meaningful differences in plasma levels of d aspartate transaminase (AST; n = 87; M.W.; Bonferroni-corrected p-value, m = 5), e alanine transaminase (ALT; n = 89; M.W.; Bonferroni-corrected p-value, m = 5), f gamma glutamyl transaminase (γ-GT; n = 89; M.W.; Bonferroni-corrected p-value, m = 5), g total bilirubin (n = 87; M.W.; Bonferroni-corrected p-value, m = 5), or h C-reactive protein (CRP; n = 85; M.W.; Bonferroni-corrected p-value, m = 5) were observed between patients who developed hepatitis and those who did not. Median values are indicated by a red line. i, j Biochemical markers of tumour burden were not different between patients who developed hepatitis and those who did not. i Pre-treatment levels of lactate dehydrogenase (n = 89; M.W.; Bonferroni-corrected p-value, m = 4). Median values are indicated by a red line. j Pre-treatment levels of protein S100 (n = 89; M.W.; Bonferroni-corrected p-value, m = 4). k–m No association was observed between seropositivity for k hepatitis B virus core antigen (HBcAg; n = 85; F.E.; Bonferroni-corrected p-value, m = 3), l hepatitis C virus (HCV; n = 85; F.E.; Bonferroni-corrected p-value, m = 3), or m hepatitis E virus (HEV; n = 67; F.E.; Bonferroni-corrected p-value, m = 3) and development of hepatitis following dual therapy. n No association was observed between rounds of αPD-1/αCTLA-4 administered and development of hepatitis (n = 89; M.W.).