Osteopontin has been identified as a promising serological biomarker for early detection of HCC and is highly complementary to AFP,[14], [15], [16], [17] while proteome multimarker panels have also been proposed.[18], [19], [20] Meanwhile, cell-free DNA methylation patterns and extracellular vesicle markers have evolved as promising surveillance tools for early HCC detection in populations at risk.[21], [22], [23], [24], [25], [26], [27] Finally, algorithms and risk scores have also been developed. This evidence concerns the gene SPP1 and hepatocellular carcinoma.