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A robust animal model for human hepatitis B virus (HBV) is needed for the discovery of novel drugs for treatment of chronic HBV infection.FRGTM (Fah-/-/Rag2-/-/I12rg-/-) triple KO mice are deficient in fumarylaceto-acetate hydrolase (FAH), which creates a chemically controllable mouse liver ablation mechanism.The animals are further modified to be immunodeficient, but are otherwise healthy.Human hepatocytes, injected intrasplenically into the mouse, can efficiently replicate to form a chimeric liver with up to 98% human cell repopulation.