Serum IL-6 is a prognostic biomarker for advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab

作者：Lorenz Kocheise, Jan Kempski, Yunhe Tang, Lorenz Balcar, Victoria Berger, Miriam Tomczak, Joao Gorgulho, Ramsha Masood, Franziska Giehren, Constantin Schmidt, Jan P. Sutter, Thorben Fründt, Francesca Pagani, Sophie Wulf, Julian Kött, Saskia Domanig, Anastasios D. Giannou, Tanja Bedke, Jöran Lücke, Tao Zhang, Siwen Zhang, Andrés Machicote, Ansgar W. Lohse, Marianna Alunni‐Fabbroni, Jens Ricke, Najib Ben Khaled, Matthias Pinter, Bernhard Scheiner, Samuel Huber, Johann von Felden, Ignazio Piseddu, Kornelius Schulze · 发表于：Annals of Hepatology · 年份：2025 · DOI：10.1016/j.aohep.2025.102138 · 被引用次数：2 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Chemokine receptors and signaling、Cytokine Signaling Pathways and Interactions

INTRODUCTION AND OBJECTIVES: Immunotherapy with atezolizumab/bevacizumab (atezo/bev) is an established first-line treatment for patients with non-resectable hepatocellular carcinoma (HCC). Despite notable successes, only a subset of patients shows treatment response, highlighting the need for biomarkers to identify those likely to benefit from this therapy. MATERIALS AND METHODS: In this biomarker study, 143 patients with atezo/bev-treated HCC were enrolled across three European centers. Baseline cytokine levels were measured using a flow cytometric multiplex bead assay. Overall survival (OS) analysis, reported as hazard ratios (HR), was conducted in an unbiased manner, with patients divided into a discovery cohort (one center, 63 patients) and a validation cohort (two centers, 80 patients). RESULTS: Our cohorts show typical baseline characteristics of Western HCC patients, with alcohol-related liver disease (35.0 %) and hepatitis C (21.7 %) as the main HCC etiologies. Elevated serum IL-6 (cut-off 18.22 pg/ml) was associated with poor OS in both the discovery (HR 2.6, 95 % CI 1.2-5.6, p = 0.013) and validation cohorts (HR 2.4, 95 % CI 1.3-4.4, p = 0.005). Multivariate analysis confirmed elevated IL-6 to be a significant prognostic biomarker of poor OS (HR 2.1, 95 % CI 1.1-3.9, p = 0.021) after adjusting for established risk factors. CONCLUSIONS: We identify elevated serum IL-6 levels as prognostic biomarker in patients with advanced HCC in Western countries. Importantly, this...