Inflammation in hepatocellular carcinoma progression: a “Single Wick, dual interwoven strands” regulatory framework

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal malignancies worldwide, with chronic liver inflammation as the core driver of its initiation and progression. Regardless of etiology, HCC development follows the classic progressive pathway of “chronic inflammation - liver fibrosis - cirrhosis - liver cancer”. In this review, we propose an innovative “Single Wick, Dual Interwoven Strands” regulatory framework to systematically delineate the role of inflammation in the entire continuum of HCC progression. We define chronic liver inflammation as the “Wick” – the core driver that initiates and sustains the pro-tumor cascade, while inflammatory cells and inflammatory cytokines act as the two interwoven functional “Strands” that execute the pro-carcinogenic effects of inflammation via a tightly regulated interactive network. Their synergistic crosstalk drives five core terminal biological outcomes of HCC progression: invasion and metastasis, angiogenesis, immune escape, metabolic reprogramming, and therapeutic resistance. Based on this framework, we dissect the core mechanisms of inflammation-driven HCC, summarize the latest advances in inflammation-targeted diagnostic, therapeutic and preventive strategies, and highlight the clinical translational prospects of this framework. This work provides systematic theoretical guidance for early prevention, precise treatment and prognosis improvement of HCC.