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

Background: 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.

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 predictor of poor OS (HR 2.1, 95% CI 1.1-3.9, p=0.021) after adjusting for established risk factors such as Child-Pugh class, BCLC stage, ECOG, macrovascular invasion, extrahepatic spread, viral HCC etiology, and AFP.

Conclusion: We identify elevated serum IL-6 levels as independent prognostic biomarker in patients with advanced HCC in Western countries. Importantly, this association was independent of infection with viral hepatitis, thus extending the previously reported associations between IL-6 and treatment response in East Asian cohorts.

Publication History

Article published online:
20 January 2025