Translating Fibrosis to Malignancy: Biomarkers and Therapeutic Opportunities in Liver Fibrosis and Hepatocellular Carcinoma

TL;DR

This paper reviews how liver fibrosis progresses to cancer and highlights shared pathways and potential therapies that could treat both conditions.

Contribution

The paper identifies shared molecular pathways between liver fibrosis and HCC, suggesting opportunities for dual-targeted therapies.

Findings

Shared pathways like TGFβ/SMAD and WNT/β-catenin are linked to both liver fibrosis and HCC.

Current biomarkers like FIB-4 and AFP are used for fibrosis and HCC detection, respectively.

Targeting pathways like TGFβ may offer dual antifibrotic and antitumor effects.

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) commonly arises from chronic liver diseases that show progressing fibrosis and cirrhosis. The molecular mechanisms driving the transition from advanced fibrosis to overt malignancy remain poorly defined, representing a key knowledge gap in current hepatology research. This review delineates shared pathways like TGFβ/SMAD, WNT/β-catenin, Hedgehog, NOTCH, Hippo/YAP-TAZ and MAPK, linking fibrosis to HCC and opening avenues for dual antifibrotic/antitumor therapies. Results and Conclusions: So far, validated biomarker tools for fibrosis, like FIB-4, Enhanced Liver Fibrosis (ELF) and combined direct/indirect markers of liver damage and tissue remodeling, are used for fibrosis staging, while HCC detection leverages serum parameters like α-fetoprotein (AFP) or, more recently, multi-omics approaches (miRNA, cfDNA, metabolomics). Understanding the interconnection of these pathways can lead to novel targeted therapies (e.g., TGFβ inhibitors) that may show dual antifibrotic and antitumor activity in future studies.

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