The Phase III REFLECT study, which compared the efficacy of lenvatinib and sorafenib in unresectable HCC, found that higher serum levels of VEGF, angiopoietin-2 (ANG2), and FGF21 were associated with a worse OS in both arms, and increased FGF21 was predictive of a reduced OS in patients treated with sorafenib [58]. This evidence concerns the gene FGF21 and hepatocellular carcinoma.