Furthermore, relapse often occurs in the absence of AIH relapse risk factors. This study aimed to identify the frequency of relapse and to analyze the risk factors associated with relapse in type 1 AIH patients. Clinical characteristics and therapeutic processes were
assessed in 129 type 1 AIH patients. Relapse was identified in 39 (30.2%) type 1 AIH patients after alanine aminotransferase (ALT) level normalization. ALT levels significantly increased when corticosteroid treatment was initiated in relapsed patients compared with that in patients with sustained remission. The reduction dose and rate of corticosteroid taper were significantly increased in relapsed patients compared with those in sustained BGJ398 mw remission patients. Moreover, positive FK228 correlations were identified between the reduction dose/taper rate and initial corticosteroid dose, and ALT levels, total bilirubin levels and hepatitis activity. Multivariate logistic regression analysis identified the corticosteroid reduction rate as significantly associated with AIH relapse. Corticosteroid reduction taper rate until ALT normalization is an important AIH relapse risk factor. “
“Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013;499:481-484.
(Reprinted with permission.) A critical shortage of donor organs for treating end-stage organ failure highlights this website the urgent need for generating organs from human induced pluripotent stem cells (iPSCs). Despite many reports describing functional cell differentiation, no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells
destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells. Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement. Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells.