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Generating functional hepatocytes independent of donor liver organs is of great interests for regenerative medicine to cure liver diseases.Induced hepatic differentiation was achieved using embryonic stem cells or induced pluripotent stem(iPS)cells.However,induction of hepatocytes from iPS cells still composes complex steps,which can be replaced by improved technology.On the other hand,the generation of large numbers of functional human hepatocytes for cell-based approaches to liver disease is an important and unmet goal.We have previously induced mouse tail-tip fibroblasts(TTFs)into functional hepatocyte-like(iHep)cells by transduction of Gata4,Hnf1a and Foxa3 and inactivation of p19Arf(1).Lately,we generated human induced hepatocyte-like(hiHep)cells from fibroblasts by forced expression of human FOXA3,HNF1A,and HNF4A(2).HiHep cells express hepatic gene programs,can be expanded in vitro,and display functions characteristic of mature hepatocytes including cytochrome P450 enzyme activity and biliary drug clearance.Upon transplantation into mice with concanavalin A-induced acute liver failure and fatal metabolic liver disease due to fumarylacetoacetate dehydrolase(Fah)deficiency,hiHep cells restore the liver function and prolong survival.Collectively,our results demonstrate successful lineage conversion of non-hepatic human cells into mature hepatocyte-like cells with potential for biomedical and pharmaceutical applications.