By gene expression and epigenomic profiling, we found that HCC livers are characterized by CAR-mediated activation of Phase I and II detoxification pathways and transporters, which promote the detoxification and excretion of toxic bile acids that accumulate in livers of Mdr2-/- mice and cause the extensive inflammation typical of the precancerous stage. The gene discussed is ABCB4; the disease is hepatocellular carcinoma.