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Interleukin-6 as a prognostic biomarker in repatocellular carcinoma treated with systemic therapy: a systematic
Yuliya V Perfilyeva1,2, Nurshat Abdolla1,2, Aikyn Kali1
1Laboratory of Molecular Immunology and Immunobiotechnology, M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty, Kazakhstan.
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.