Front Pharmacol. 2025 Oct 17;16:1697608. doi: 10.3389/fphar.2025.1697608. eCollection 2025.

ABSTRACT

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death, and recovery after therapy is shaped by heterogeneous etiologies, genomes and microenvironments. Targeted and immunotherapy combinations have broadened first-line options; yet durable benefit is uneven, and serum/imaging anchors (AFP, AFP-L3%, PIVKA-II, LI-RADS/mRECIST) incompletely resolve residual disease or functional restoration. In this review we summarise AI-enabled radiology, digital pathology and multi-omic/liquid-biopsy analytics that test and refine traditional biomarkers and drug-target readouts, and appraise translational opportunities in composite surveillance and recovery forecasting. We also discuss enduring challenges-including assay standardisation, spectrum bias, data leakage, domain shift and limited prospective external validation-that temper implementation. By integrating established anchors (AFP/AFP-L3%, PIVKA-II, ALBI, contrast-enhanced hallmarks) with AI-derived signals (radiomics/pathomics, cfDNA methylation) and pathway contexts (VEGF-VEGFR, WNT/β-catenin), emerging strategies align predictions with clinical endpoints, individualise therapy and chart hepatic function. Our synthesis provides an appraisal of AI-traditional integration in liver cancer recovery and outlines pragmatic standards-analytical robustness, transparent reporting and prospective, guideline-conformant evaluation-required for clinical adoption. We hope these insights will aid researchers and clinicians as they implement more effective, individualised monitoring and treatment pathways.

PMID:41181592 | PMC:PMC12575369 | DOI:10.3389/fphar.2025.1697608