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The incidence of AFP-negative HCC is increasing worldwide, particularly HCCs of nonviral etiology, such as MASLD/MASH. A high percentage of patients with MASLD/MASH-related HCC are positive for PIVKA-II, even those who are negative for AFP[1]. Higher levels of AFP-L3 have also been reported in cases of MASLD/MASH-related HCC [2]. Thus, the role of PIVKA-II and AFP-L3 measurements in HCC surveillance and diagnosis of AFP-negative HCCs has become more important.
This article by Prof Masatoshi Kudo details the importance of testing all 3 biomarkers, AFP, AFP-L3, and PIVKA-II, in HCC surveillance and management. He also discusses new algorithms, such as GALAD and GAAD, which incorporate these biomarkers have been useful in countries where access to imaging is limited.