New research published in *Hepatology International* has illuminated the critical link between liver fibrosis and hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. The study details how chronic liver damage transforms healthy tissue into a pro-cancerous surroundings, with over 80% of HCC cases originating from advanced fibrosis or cirrhosis.

At the heart of this change are hepatic stellate cells (hscs). When activated by persistent liver injury, such as from viral hepatitis or excessive alcohol consumption, HSCs initiate the deposition of stiff scar tissue. This scar tissue isn’t merely structural; it actively secretes molecules that promote tumor development, such as VEGF and Ang-1, which fuel blood vessel growth for tumors. Moreover, these activated HSCs can suppress the body’s immune response by expressing PD-L1, effectively hiding cancer cells from immune surveillance. In a concerning development, HSCs can also morph into cancer-associated fibroblasts (CAFs), which further accelerate the progression of malignancy.

The review also highlights the role of disrupted cellular signaling pathways, including TGF-β‑smad, NF-κB, and Wnt, alongside changes in the extracellular matrix (ECM), mitochondrial function, and epigenetic modifications.These cumulative alterations create a microenvironment within the liver that is highly conducive to cancer formation.

“This fibrosis-to-cancer axis isn’t inevitable,” stated co-author Dr.Peng Luo of Southern Medical University. “By targeting key mechanisms – like HSC activation or immune evasion – we can intercept progression before malignancy takes hold.”

Promising therapeutic avenues are emerging, including:

• Liquid Biopsies: These advanced diagnostic tools can detect tumor DNA and exosomes in bodily fluids, offering the potential for early cancer detection.
• CAF-targeting Therapies: Treatments aimed at disrupting the tumor-supportive niches created by CAFs, such as FAP inhibitors and CAR-T cell therapies, are showing promise.
• Combination Therapies: Strategies that simultaneously target fibrosis drivers and bolster the immune system, including immune checkpoint inhibitors, are being explored to prevent the transition to cancer.

The research team stressed the critical importance of early intervention. “Reversing fibrosis is possible, but once HCC develops, prognosis plummets. Our findings spotlight actionable checkpoints to prevent this transition,” they emphasized.