Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors

Risk factors for hepatic immune-related adverse events (HIRAEs) in patients with advanced/unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are unclear. We investigated: (i) clinical and morpho-pathological predictors of HIRAEs in 27 pretreatment tumor spec...

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Autores principales:	Nicola Personeni, Tiziana Pressiani, Antonio D’Alessio, Maria Giuseppina Prete, Silvia Bozzarelli, Luigi Terracciano, Arianna Dal Buono, Antonio Capogreco, Alessio Aghemo, Ana Lleo, Romano Fabio Lutman, Massimo Roncalli, Laura Giordano, Armando Santoro, Luca Di Tommaso, Lorenza Rimassa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hepatotoxicity hepatocellular carcinoma immune checkpoint inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3222d708afd849bdbecd0208aa93d8c8
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spelling	oai:doaj.org-article:3222d708afd849bdbecd0208aa93d8c82021-11-25T17:02:27ZHepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors10.3390/cancers132256652072-6694https://doaj.org/article/3222d708afd849bdbecd0208aa93d8c82021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5665https://doaj.org/toc/2072-6694Risk factors for hepatic immune-related adverse events (HIRAEs) in patients with advanced/unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are unclear. We investigated: (i) clinical and morpho-pathological predictors of HIRAEs in 27 pretreatment tumor specimens, including surrogate biomarkers of the HCC immune class (based on intratumoral tertiary lymphoid structures, and glutamine synthase, CD3, and CD79 expression); and (ii) the relationship between HIRAE onset and subsequent treatment outcomes. Fifty-eight patients were included—20 (34%) received ICIs alone, and 38 (66%) received ICIs plus targeted agents as first- or further-line treatment. After a median time of 0.9 months (range, 0.4–2.7), nine patients (15.5%) developed grade ≥ 3 hepatitis, which was significantly associated with higher baseline ALT levels (<i>p</i> = 0.037), and an infectious HCC etiology (<i>p</i> = 0.023). ICIs were safely resumed in six out of nine patients. Time to treatment failure (TTF) was not significantly different in patients developing grade ≥ 3 hepatitis vs. lower grades (3.25 vs. 3.91 months, respectively; <i>p</i> = 0.81). Biomarker surrogates for the HCC immune class were not detected in patients developing grade ≥ 3 hepatitis. Grade ≥ 3 hepatitis has a benign course that does not preclude safe ICI reintroduction, without any detrimental effect on TTF.Nicola PersoneniTiziana PressianiAntonio D’AlessioMaria Giuseppina PreteSilvia BozzarelliLuigi TerraccianoArianna Dal BuonoAntonio CapogrecoAlessio AghemoAna LleoRomano Fabio LutmanMassimo RoncalliLaura GiordanoArmando SantoroLuca Di TommasoLorenza RimassaMDPI AGarticlehepatotoxicityhepatocellular carcinomaimmune checkpoint inhibitorsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5665, p 5665 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatotoxicity hepatocellular carcinoma immune checkpoint inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatotoxicity hepatocellular carcinoma immune checkpoint inhibitors Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Nicola Personeni Tiziana Pressiani Antonio D’Alessio Maria Giuseppina Prete Silvia Bozzarelli Luigi Terracciano Arianna Dal Buono Antonio Capogreco Alessio Aghemo Ana Lleo Romano Fabio Lutman Massimo Roncalli Laura Giordano Armando Santoro Luca Di Tommaso Lorenza Rimassa Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors
description	Risk factors for hepatic immune-related adverse events (HIRAEs) in patients with advanced/unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) are unclear. We investigated: (i) clinical and morpho-pathological predictors of HIRAEs in 27 pretreatment tumor specimens, including surrogate biomarkers of the HCC immune class (based on intratumoral tertiary lymphoid structures, and glutamine synthase, CD3, and CD79 expression); and (ii) the relationship between HIRAE onset and subsequent treatment outcomes. Fifty-eight patients were included—20 (34%) received ICIs alone, and 38 (66%) received ICIs plus targeted agents as first- or further-line treatment. After a median time of 0.9 months (range, 0.4–2.7), nine patients (15.5%) developed grade ≥ 3 hepatitis, which was significantly associated with higher baseline ALT levels (<i>p</i> = 0.037), and an infectious HCC etiology (<i>p</i> = 0.023). ICIs were safely resumed in six out of nine patients. Time to treatment failure (TTF) was not significantly different in patients developing grade ≥ 3 hepatitis vs. lower grades (3.25 vs. 3.91 months, respectively; <i>p</i> = 0.81). Biomarker surrogates for the HCC immune class were not detected in patients developing grade ≥ 3 hepatitis. Grade ≥ 3 hepatitis has a benign course that does not preclude safe ICI reintroduction, without any detrimental effect on TTF.
format	article
author	Nicola Personeni Tiziana Pressiani Antonio D’Alessio Maria Giuseppina Prete Silvia Bozzarelli Luigi Terracciano Arianna Dal Buono Antonio Capogreco Alessio Aghemo Ana Lleo Romano Fabio Lutman Massimo Roncalli Laura Giordano Armando Santoro Luca Di Tommaso Lorenza Rimassa
author_facet	Nicola Personeni Tiziana Pressiani Antonio D’Alessio Maria Giuseppina Prete Silvia Bozzarelli Luigi Terracciano Arianna Dal Buono Antonio Capogreco Alessio Aghemo Ana Lleo Romano Fabio Lutman Massimo Roncalli Laura Giordano Armando Santoro Luca Di Tommaso Lorenza Rimassa
author_sort	Nicola Personeni
title	Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors
title_short	Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors
title_full	Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors
title_fullStr	Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors
title_full_unstemmed	Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors
title_sort	hepatotoxicity in patients with hepatocellular carcinoma on treatment with immune checkpoint inhibitors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3222d708afd849bdbecd0208aa93d8c8
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Hepatotoxicity in Patients with Hepatocellular Carcinoma on Treatment with Immune Checkpoint Inhibitors

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