Interleukin-6 as a prognostic biomarker in repatocellular carcinoma treated with systemic therapy: a systematic review and meta-analysis

Background and aims: Interleukin-6 (IL-6) has been implicated in the pathogenesis of hepatocellular carcinoma (HCC) and resistance to systemic therapy. This study aimed to evaluate the prognostic value of circulating IL-6 in patients with HCC receiving systemic therapy through a systematic review and meta-analysis. Methods: A systematic literature search was conducted in PubMed, Web of Science, Scopus, and ClinicalTrials.gov from database inception to 27 July 2026. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: Thirteen studies comprising 1,504 patients were included. Elevated baseline IL-6 was significantly associated with worse OS (hazard ratio [HR] = 2.29, 95%, confidence interval [CI]: 1.87–2.81; p < 0.001), PFS (HR = 1.70, 95% CI: 1.39–2.07; p < 0.001), ORR (odds ratio [OR] = 0.37, 95% CI: 0.23–0.59; p < 0.001), and DCR (OR = 0.39, 95% CI: 0.19–0.78; p = 0.008). Evidence regarding the prognostic value of on-treatment IL-6 concentrations and longitudinal changes during therapy was limited and heterogeneous. Conclusions: High baseline IL-6 is associated with poor prognosis and reduced treatment response in HCC patients receiving systemic therapy, warranting further treatment-specific evaluation of its prognostic utility. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD420261456976.