Obtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2(-/-)/γc(-/-) mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications.

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Summary The aim of this study was to explore the feasibility of emergency right lobe adult‐to‐adult living‐donor liver transplantation (LDLT) for high model for end‐stage liver disease (MELD) score severe hepatitis. Consecutive 10 high MELD score severe hepatitis patients underwent emergency right lobe adult‐to‐adult LDLT in our hospital from April to December 2007. The MELD score was 34.50 ± 2.088. The outcomes of these recipients were retrospectively analyzed. Among them, eight cases of ABO blood group were identical and two cases compatible, one case was Rh negative. Two recipients died and the rest of the recipients and all donors are safe; perioperative and 2‐year survival rate was 80%. The mean graft‐recipient weight ratio (GRWR) was 1.27% ± 0.25%, and graft volume to recipient standard liver volume ratio (GV/ESLVR) was 56.7% ± 6.75%. Of the 10 patients, three received right lobe grafts with middle hepatic vein (MHV), four without MHV, three without MHV but followed by V and VIII hepatic vein outflow reconstruction. An encouraging outcome was achieved in this group: elevated serum creatinine, serum endotoxin, decreased serum prothrombin activity, and Tbil returned to normal on postoperative days 3, 7, 14, and 28, respectively. One‐year survival rate was 80%. Outcomes of emergency right lobe adult‐to‐adult LDLT for high MELD score severe hepatitis were fairly encouraging and acceptable. Emergency right lobe adult‐to‐adult LDLT is an effective and life‐saving modality for high MELD score acute liver failure patients following severe hepatitis.