Gender, Age, Alpha-fetoprotein, and Des-gamma-carboxyprothrombin Score as a Novel Approach to Early Detection of Hepatocellular Carcinoma: A Narrative Review

Hepatocellular carcinoma (HCC) represents the most serious consequence of chronic liver disease and constitutes over 80% of primary liver cancers globally. In individuals with cirrhosis, the annual incidence of HCC ranges between 1% and 8%, highlighting the critical need for effective screening methods to enable early diagnosis and prompt treatment. Currently, abdominal ultrasound is the main surveillance modality endorsed by international guidelines, with biannual screening intervals demonstrating improved survival compared to annual assessments. However, ultrasound faces notable limitations, particularly in identifying tumors smaller than 2 cm, with sensitivity dropping to 47%. Its diagnostic performance is further hindered by factors such as obesity, ascites, and hepatic steatosis, and it remains highly dependent on the operator’s skill, leading to variability in results. To overcome these obstacles, blood-based biomarkers such as alpha-fetoprotein and protein induced by vitamin K absence-II have been explored for early HCC detection. Recently, novel diagnostic tools like Gender, Age, Alpha-fetoprotein, and Des-gamma-carboxyprothrombin (GAAD) score have emerged, showing promise in refining surveillance efficacy. Nevertheless, despite encouraging preliminary data, integrating the GAAD score into routine clinical practice is still limited pending further validation. This narrative review explores the potential of the GAAD score as a biomarker for early-stage HCC, assessing its value in complementing and enhancing existing surveillance protocols.