Current imaging methods and molecular biomarkers for hepatocellular carcinoma diagnosis: a narrative review.
Authors
Affiliations (11)
Affiliations (11)
- School of Bioscience, Faculty of Pharmacy and Biomedical Sciences, MAHSA University, Jenjarom, Malaysia.
- Department of Biomedical Sciences, Faculty of Medical and Life Sciences Sunway University, Petaling Jaya, Malaysia.
- Sunway Microbiome Centre, Faculty of Medical and Life Sciences Sunway University, Petaling Jaya, Malaysia.
- Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Bedong, Malaysia.
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia.
- Global Research Cell, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, India.
- Department of Neonatology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India.
- Department of Electrical and Electronics Engineering, Dogus University, Umraniye, Istanbul, Türkiye.
- Faculty of Chemical Engineering & Technology, Universiti Malaysia Perlis (UniMAP), Arau, Malaysia.
- School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, Malaysia.
- Collaborative Drug Discovery Research (CDDR), Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Puncak Alam, Malaysia.
Abstract
Hepatocellular carcinoma (HCC) is one the seventh most prevalent form of cancer in the world and the third highest cause of cancer fatalities in different parts of the world, mostly due to the late diagnosis. and primarily associated with chronic liver diseases. HCC is heavily linked and associated with hepatitis B and C infections, as well as lifestyle factors such as heavy alcohol consumption, obesity, and diabetes. This narrative review critically evaluates current diagnostic approaches for HCC, including imaging modalities, liver biopsy, and established and emerging molecular biomarkers, while highlighting recent advances, existing limitations, and future diagnostic strategies. A narrative literature search was conducted using PubMed, Scopus, Google Scholar, and Web of Science to identify relevant English-language publications from 2009 to 2026. Original research articles, systematic reviews, meta-analyses, and clinical practice guidelines related to HCC diagnosis and surveillance were considered. The search terms covered HCC, imaging modalities, biomarkers, GALAD, GAAD, microRNA, and liquid biopsy. Guidelines from the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Asian Pacific Association for the Study of the Liver (APASL) were also reviewed. The reviewed evidence indicates that multiphasic computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) remain key imaging modalities for HCC diagnosis. Emerging biomarkers including des-γ-carboxy prothrombin (DCP), fibroblast growth factor 19 (FGF19), various microRNAs (miRNAs), and osteopontin (OPN), circulating microRNAs (miRNAs), show diagnostic potential, particularly when incorporated into multimarker panels or combined with conventional biomarkers such as alpha-fetoprotein (AFP). Artificial intelligence-assisted imaging and multimarker diagnostic models may also support earlier and more accurate detection. However, wider clinical implementation remains limited by insufficient multicentre validation, lack of assay standardization, limited reproducibility, and insufficient cost-effectiveness evidence. Modern diagnostic methods increasingly incorporate these imaging tools alongside molecular markers to yield a more accurate diagnosis and optimal treatment strategy. While liver biopsy remains the gold standard for histopathological confirmation, its invasive nature and associated risks highlight the urgent need for reliable, non-invasive diagnostic alternatives. This review provides insights into the current strategies to diagnose HCC and with an emphasis on innovative diagnostic strategies.