Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Its incidence is steadily increasing due to the global rise in chronic liver diseases such as hepatitis B and C, alcoholic liver disease, and metabolic dysfunction – associated steatotic liver disease (MASLD). Early detection remains critical, as 30–40% of patients present at advanced stages with limited treatment options and a 5-year survival rate below 20%.

 Serum alpha-fetoprotein (AFP), a glycoprotein elevated in 60–70% of HCC cases, has traditionally been used for screening but suffers from poor sensitivity (18–60%) and specificity (85–90%), particularly in early-stage tumours. For instance, AFP fails to detect 80% of HCC nodules <3 cm, and its levels can rise non-specifically during hepatic inflammation or regeneration. 

 In recent years, des-gamma-carboxy prothrombin, also known as PIVKA-II (Protein Induced by Vitamin K Antagonist-II), has emerged as a promising complementary biomarker with better performance in certain clinical settings. Studies have reported 81.55 % sensitivity and 86 % specificity at cutoff values of 43.47 mAU/mL. Unlike AFP, PIVKA-II levels correlate with tumour aggressiveness and vascular invasion, making it valuable for monitoring progression. 

 To enhance diagnostic accuracy, composite scoring systems such as the ASAP score—which integrates Age, Sex, AFP, and PIVKA-II—have been developed and evaluated in various populations. These multiparametric tools may improve early detection and allow risk stratification, but their clinical utility in different ethnic and demographic groups, including the Indian population, remains underexplored.

 Moreover, the correlation between biomarker levels and the histological grade or clinical stage of HCC could provide valuable prognostic insights and support the development of personalized therapeutic strategies .

This study aims to compare the diagnostic efficacy of AFP, PIVKA-II, and the ASAP score in the detection of HCC and to analyse their correlation with tumour grade and severity in a population mix in Tertiary care Hospital, thereby contributing to a more refined and personalized approach to HCC diagnosis.