Decision-Making Biomarkers Guiding Therapeutic Strategies in Hepatocellular Carcinoma: From Prediction to Personalized Care.

Hepatocellular carcinoma (HCC) management has evolved remarkably with the advent of diverse therapeutic options, particularly systemic and surgical treatments. Combination immunotherapy has redefined the treatment paradigm for advanced HCC and contributed to improved patient outcomes. However, this brings forth challenges such as immune-related adverse events that complicate decision-making. Surgical strategies have expanded with the emergence of conversion therapy and borderline resectability, offering curative potential for a broader patient population. However, robust evidence of their long-term efficacy is lacking. Therefore, decision-making biomarkers have gained prominence across treatment modalities. This review explores the current landscape of predictive, prognostic, and treatment-response biomarkers in HCC, from molecular and immune signatures to radiological and biochemical markers, highlighting their role in optimizing therapeutic strategies. By integrating recent advances in basic and translational research with clinical practice, we aim to outline a biomarker-driven framework for individualized care in HCC.