Overall, our results reported herein demonstrate that rAAV8 vectors containing either the liver-specific TTR promoter or the strong CB promoter that either contain or lack a PolyA sequence and the transgene encoding human FIX have distinct effects on liver and spleen health yet caused no HCC development during the 6.5-month experiments in the inbred C57BL/6 or the Balb/C hemophilia B mouse models. Here, TTR is linked to hepatocellular carcinoma.