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Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

ABSTRACT: In this study we conducted transcriptomics analyses of: (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (n=3) and from healthy livers (n=2) and (ii) hepatic cell systems exposed to acetaminophen, including their respective vehicle controls. The investigated in vitro systems are: HepaRG cells, HepG2 cells and a novel human skinpostnatal stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Clinical samples were obtained after surgical removal of the explant liver of patients diagnosed with ALF due to acetaminophen intoxication and treated by orthotopic liver transplantation (n=3). Samples from healthy livers were obtained from individuals deceased from brain damage (n=2).

ORGANISM(S): Homo sapiens

PROVIDER: GSE74000 | GEO | 2015/11/04

SECONDARY ACCESSION(S): PRJNA298696

REPOSITORIES: GEO

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Project description:Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome due to a sudden loss of hepatic cells leading to multiorgan failure. The mechanisms whereby HBV induces ALF are unknown. We used gene expression profiling to establish a molecular definition of hepatitis B virus (HBV)-associated ALF. Two patients who underwent liver transplantation for HBV-associated ALF were studied. Gene expression profiling was performed on 8 liver specimens obtained from the two patients with ALF (4 samples per liver) and individual liver specimens from 8 liver donors and normal livers from 11 patients who underwent resection for angioma. Statistical analyses were used to identify the signature genes of HBV-associated ALF. Multivariate permutation analysis identified 1,368 transcripts that were differentially expressed in ALF; 709 were up-regulated and 659 down-regulated. The most represented up-regulated transcripts were those involved in the immune response, whereas the most abundant down-regulated transcripts were those involved in metabolism and hepatic synthesis. ALF was characterized by overriding B-cell signature comprising genes related to mature B cells and plasma cells with abundant polyclonal expression of immunoglobulin genes. By contrast, there was a limited T-cell signature and up-regulation of several inhibitors of T-cell activation. Immunohistochemical analysis confirmed the prominent B-cell signature showing diffuse liver infiltration by plasma blasts and plasma cells with strong cytoplasmic staining for IgM and IgG, associated with a significant deposition of complement factors. Using phage display technology, we demonstrated that the molecular target of the massive intrahepatic antibody response is the hepatitis B core antigen (HBcAg). These data suggest that the humoral immunity may exert a primary role in the pathogenesis of HBV-associated ALF. Liver samples were obtained from explanted livers of two patients with HBV-associated ALF (4 samples per liver), 8 normal liver donors and 11 patients who underwent resection for angioma. Gene expression profiling was used to establish a molecular definition of ALF. Patient data derived from associated publication Table S2. This dataset is part of the TransQST collection.

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Gene expression data from acetaminophen-induced toxicity in human hepatic in vitro systems and clinical liver samples

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