Early mortality in atezolizumab/bevacizumab for HCC is associated with impaired liver function and alterations of systemic immunity

作者：Ignazio Piseddu, Leonie Jochheim, Katrin Böttcher, Bernhard Scheiner, Friedrich Sinner, Simon Johannes Gairing, Matthias Thaler, Stefan Enßle, Monika Karin, Valentina Zarka, Alexander Philipp, Andreas Thalmeier, Jan Gaertig, Lorenz Balcar, Julia Martina Schütte, Julia S. Schneider, Katarina Ondrejkova, Monika Rau, Alexander Weich, David Anz, Karin Berger, Christian Schulz, Christian M. Lange, Osman Öcal, Marianna Alunni‐Fabbroni, Jens Ricke, Ursula Ehmer, Marino Venerito, Friedrich Foerster, Matthias Pinter, Andreas Geier, Julia Mayerle, Enrico N. De Toni, Florian P. Reiter, Najib Ben Khaled · 发表于：JHEP Reports · 年份：2025 · DOI：10.1016/j.jhepr.2025.101513 · 被引用次数：4 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research

Background & Aims Atezolizumab/bevacizumab (atezo/bev) has revolutionized the standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, only a subgroup of patients responds to atezo/bev and derives durable clinical benefit. This study aims to analyze the frequency and risk factors of early mortality (EM) in patients with HCC treated with atezo/bev. Methods This study uses data from a large, European real-world cohort and flow cytometry-based immunophenotyping of patient's baseline PBMC. EM was defined as death from any cause within 90 days of treatment initiation. Logistic regression analysis was used to identify parameters associated with EM. Results A total of 317 patients with unresectable HCC treated with first-line atezo/bev were included. EM rate in the cohort was 15.8%, with a median survival of 12.6 months. The proportion of patients with preserved liver function and BCLC stage B was significantly lower in the EM cohort. The strongest predictor of EM was advanced liver disease in univariate analysis, as reflected by surrogates of impaired liver function such as Child–Pugh score (CPS) B ( p <0.0001), albumin–bilirubin grade 2/3 ( p = 0.026, p <0.0001) or high model for end-stage liver disease score ( p <0.0001). CPS B remained a significant risk factor after adjusting for other variables. Biomarker analysis and immunophenotyping revealed high C-reactive protein, reduced lymphocyte frequencies, increased CD44 expression on regulatory T cel...