These results support the notion that hyperbilirubinemia in Fech-mut/Oatp1a/1b-KO mice arises from a synergistic effect of Oatp1a/1b deficiency and PPIX-mediated bile duct blockage, because Oatp1a/1b deficiency impairs CB uptake from plasma, while PPIX-induced bile duct obstruction slows CB excretion from the liver, collectively leading to increased CB redistribution into the bloodstream (Fig. 6E). This evidence concerns the gene FECH and cholestasis.