A second hypothesis regarding the cause of elevated FGF21 levels before the onset of appetite loss in patients with grade ≥ 2 appetite loss after lenvatinib treatment for unresectable HCC is that a fasting or pre-cachexia status may be established before the onset of severe appetite loss in treated patients [27,28], resulting in the elevation of FGF21 levels before the onset of severe appetite loss. Here, FGF21 is linked to Cachexia.