Genotype‐specific interactions of insulin resistance, steatosis, and fibrosis in chronic hepatitis C

Ian Homer Y. Cua, Jason M. Hui, James G. Kench, Jacob George – 2 May 2008 – The interaction between insulin resistance (IR), steatosis and genotype to fibrosis in chronic hepatitis C virus (HCV) infection has not been comprehensively assessed. We hypothesized that IR is a key mediator for the development of both steatosis and fibrosis in 346 untreated, nondiabetic patients solely infected with either genotype 1 or 3. We examined for genotype‐specific interactions between IR, steatosis and fibrosis by performing subgroup analyses.

Genetic polymorphism of hepatocyte nuclear factor‐4α influences human cytochrome P450 2D6 activity

Sang Seop Lee, Eun‐Young Cha, Hyun‐Ju Jung, Ji‐Hong Shon, Eun‐Young Kim, Chang‐Woo Yeo, Jae‐Gook Shin – 2 May 2008 – Hepatocyte nuclear factor‐4 alpha (HNF4A) is an essential transcriptional regulator for many genes that are expressed preferentially in the liver. Among the important functions of the liver is drug metabolism in response to xenobiotic exposure. Recent studies have suggested that HNF4A regulates the expression of cytochrome P450 (CYP), including CYP2D6 and CYP3A4, which show large individual variations in their activities.

Pathogenic role of natural killer T and natural killer cells in acetaminophen‐induced liver injury in mice is dependent on the presence of dimethyl sulfoxide

Mary Jane Masson, Leah D. Carpenter, Mary L. Graf, Lance R. Pohl – 2 May 2008 – Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. Although DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked.

Murine cirrhosis induces hepatocyte epithelial mesenchymal transition and alterations in survival signaling pathways

Takashi Nitta, Jae‐Sung Kim, Dagmara Mohuczy, Kevin E. Behrns – 2 May 2008 – Hepatocytes that reside in a chronically‐injured liver have altered growth responses compared to hepatocytes in normal liver. Transforming growth factor beta (TGFβ) is upregulated in the cirrhotic liver, and cirrhotic hepatocytes, unlike normal hepatocytes exposed to this cytokine, exhibit decreased apoptosis. In fetal hepatocytes, TGFβ also induces epithelial‐mesenchymal transition (EMT) and signaling changes in cell survival pathways.

Activation of nuclear factor E2‐related factor 2 in hereditary tyrosinemia type 1 and its role in survival and tumor development

Silke Marhenke, Jutta Lamlé, Laura Elisa Buitrago‐Molina, José Manuel Fernández Cañón, Robert Geffers, Milton Finegold, Michael Sporn, Masayuki Yamamoto, Michael P. Manns, Markus Grompe, Arndt Vogel – 2 May 2008 – In tyrosinemia type 1 (HT1), accumulation of toxic metabolites results in oxidative stress and DNA damage, leading to a high incidence of hepatocellular carcinomas. Nuclear factor erythroid‐2 related factor 2 (Nrf2) is a key transcription factor important for cellular protection against oxidative stress and chemical induced liver damage.

In vivo antisense oligonucleotide reduction of NPC1 expression as a novel mouse model for Niemann Pick type C– associated liver disease

Victoria M. Rimkunas, Mark J. Graham, Rosanne M. Crooke, Laura Liscum – 25 April 2008 – Niemann‐Pick type C (NPC) is a fatal autosomal recessive lipidosis that is characterized by lysosomal storage of cholesterol and glycosphingolipids. Patients exhibit prolonged neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration that generally result in death by the teen years. Most clinical cases are caused by mutations in the NPC1 gene. Current mouse models of NPC are not well suited for studying the liver disease due to the rapidly progressing neurological disease.

Subscribe to