The shift toward multi-dimensional scores such as HES (HCC Early Detection Screening), GALAD (Gender, Age, AFP-L3, AFP, and DCP), ASAP (Age, Sex, AFP, PIVKA-II), and mt-HTB (Multitarget HCC Blood Test) represents a significant advancement in biomarker research for hepatocellular carcinoma (HCC) detection. Unlike single biomarker approaches, these scores integrate various clinical and biochemical factors to enhance predictive accuracy by reflecting different complementary aspects of disease progression and HCC oncogenesis. Proper testing and validation of biomarker scores in phase 3 biomarker studies is essential before wide use can be recommended. The comparative performance of biomarker scores in phase 3 studies is reviewed. HES V2.0 includes AFP, AFP-L3, DCP (and changes in their level in the past one year), age, platelets, albumin, ALT, and underlying liver disease etiology in a predictive model. At a fixed 90% specificity, HES V2.0 outperforms GALAD and ASAP in early-stage HCC detection in phase 3 biomarker studies. HES V2.0 improves sensitivity by 6.7% over GALAD and by 13.4%-18.0% over ASAP. The evolution toward multi-dimensional scores marks a significant advancement in HCC biomarker research, offering improved diagnostic precision. However, ongoing validation, regional performance analyses, and cost-effectiveness evaluations are pivotal to their clinical implementation.
