Hepatocellular Carcinoma in the Twenty-First Century: Risk-Adapted Surveillance, Biomarkers, and Evolving Therapeutic Strategies

Abstract

Introduction and Purpose

The increasing contribution of metabolic dysfunction-associated steatotic liver disease (MASLD) to hepatocellular carcinoma (HCC) has highlighted important limitations of conventional ultrasound-based surveillance. Obesity, hepatic steatosis, and heterogeneous liver parenchyma may impair visualization and reduce sensitivity for early-stage tumors. This review summarizes current evidence on HCC risk stratification, surveillance, diagnosis, and treatment, with particular emphasis on risk-adapted strategies in patients with MASLD.

Materials and Methods

Peer-reviewed literature was reviewed, with emphasis on studies addressing ultrasound-based surveillance, abbreviated magnetic resonance imaging (AMRI), elastography, biomarker-based risk models, liquid biopsy, radiomics, artificial intelligence, and recent advances in locoregional and systemic treatment.

Results

Ultrasound with or without alpha-fetoprotein remains the standard surveillance strategy for patients at increased risk of HCC, although its effectiveness is reduced when visualization is inadequate. In selected patients, alternative imaging approaches, including AMRI, may improve surveillance performance. Elastography, clinical risk models, and biomarker panels such as GALAD may support risk stratification, whereas liquid biopsy, radiomics, and artificial intelligence remain investigational. Advances in locoregional therapy, immunotherapy, and targeted therapy have also expanded treatment options across different stages of HCC.

Conclusion

The key challenge is to identify patients in whom ultrasound-based surveillance is insufficient rather than to replace ultrasonography universally. A risk-adapted strategy integrating individual HCC risk, ultrasound quality, and selected complementary tools may be particularly relevant in MASLD. Further prospective studies are needed to determine whether such approaches improve early detection and clinical outcomes.