A phase 2, randomized, double‐blind, placebo‐controlled study of GS‐9450 in subjects with nonalcoholic steatohepatitis

Vlad Ratziu, Muhammad Y. Sheikh, Arun J. Sanyal, Joseph K. Lim, Hari Conjeevaram, Naga Chalasani, Manal Abdelmalek, Anezi Bakken, Christophe Renou, Melissa Palmer, Robert A. Levine, B. Raj Bhandari, Melanie Cornpropst, Wei Liang, Benjamin King, Elsa Mondou, Franck S. Rousseau, John McHutchison, Mario Chojkier – 17 October 2011 – In nonalcoholic steatohepatitis (NASH), the extent of hepatocyte apoptosis correlates with disease severity. Reducing hepatocyte apoptosis with the selective caspase inhibitor GS‐9450 has a potential for altering the course of the liver disease.

Biochemical and immunologic effects of rituximab in patients with primary biliary cirrhosis and an incomplete response to ursodeoxycholic acid

Masanobu Tsuda, Yuki Moritoki, Zhe‐Xiong Lian, Weici Zhang, Katsunori Yoshida, Kanji Wakabayashi, Guo‐Xiang Yang, Toshio Nakatani, John Vierling, Keith Lindor, M. Eric Gershwin, Christopher L. Bowlus – 17 October 2011 – The aim of this study was to determine the safety and potential efficacy of B‐cell depletion with the anti‐CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA).

Prospective biopsy‐controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis

Diana Joka, Kristin Wahl, Sarah Moeller, Jerome Schlue, Bernhard Vaske, Matthias J. Bahr, Michael P. Manns, Klaus Schulze‐Osthoff, Heike Bantel – 12 October 2011 – Fibrosis and steatosis are major histopathological alterations in chronic liver diseases. Despite various shortcomings, disease severity is generally determined by liver biopsy, emphasizing the need for simple noninvasive methods for assessing disease activity.

CD133+ liver tumor‐initiating cells promote tumor angiogenesis, growth, and self‐renewal through neurotensin/interleukin‐8/CXCL1 signaling

Kwan Ho Tang, Stephanie Ma, Terence K. Lee, Yuen Piu Chan, Pak Shing Kwan, Carol M. Tong, Irene O. Ng, Kwan Man, Ka‐Fai To, Paul B. Lai, Chung‐Mau Lo, Xin‐Yuan Guan, Kwok Wah Chan – 12 October 2011 – A novel theory in the field of tumor biology postulates that cancer growth is driven by a population of stem‐like cells, called tumor‐initiating cells (TICs). We previously identified a TIC population derived from hepatocellular carcinoma (HCC) that is characterized by membrane expression of CD133.

Mortality and the risk of malignancy in autoimmune liver diseases: A population‐based study in Canterbury, New Zealand

Jing Hieng Ngu, Richard Blair Gearry, Chris Miles Frampton, Catherine Ann Malcolm Stedman – 12 October 2011 – Population‐based quantitative data on the mortality and cancer incidence of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) are scarce. Our aim was to systematically investigate the survival and risk of malignancy on population‐based cohorts of AIH, PBC, and PSC in Canterbury, New Zealand.

Molecular perturbations restrict potential for liver repopulation of hepatocytes isolated from non–heart‐beating donor rats

Yuta Enami, Brigid Joseph, Sriram Bandi, Juan Lin, Sanjeev Gupta – 12 October 2011 – Organs from non–heart‐beating donors are attractive for use in cell therapy. Understanding the nature of molecular perturbations following reperfusion/reoxygenation will be highly significant for non–heart‐beating donor cells. We studied non–heart‐beating donor rats for global gene expression with Affymetrix microarrays, hepatic tissue integrity, viability of isolated hepatocytes, and engraftment and proliferation of transplanted cells in dipeptidyl peptidase IV‐deficient rats.

Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis

Alessia Bersagliere, Iolanda D. Raduazzo, Mariateresa Nardi, Sami Schiff, Angelo Gatta, Piero Amodio, Peter Achermann, Sara Montagnese – 12 October 2011 – In patients with cirrhosis, hyperammonemia and hepatic encephalopathy are common after gastrointestinal bleeding and can be simulated by an amino acid challenge (AAC), or the administration of a mixture of amino acids mimicking the composition of hemoglobin. The aim of this study was to investigate the clinical, psychometric, and wake‐/sleep‐electroencephalogram (EEG) correlates of induced hyperammonemia.

AKT (v‐akt murine thymoma viral oncogene homolog 1) and N‐Ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mTOR (mammalian target of rapamycin complex 1), FOXM1 (forkhead box M1)/SKP2,

Coral Ho, Chunmei Wang, Sandra Mattu, Giulia Destefanis, Sara Ladu, Salvatore Delogu, Julia Armbruster, Lingling Fan, Susie A. Lee, Lijie Jiang, Frank Dombrowski, Matthias Evert, Xin Chen, Diego F. Calvisi – 12 October 2011 – Activation of v‐akt murine thymoma viral oncogene homolog (AKT) and Ras pathways is often implicated in carcinogenesis. However, the oncogenic cooperation between these two cascades in relationship to hepatocellular carcinoma (HCC) development remains undetermined.

Vitamin D deficiency in obese rats exacerbates nonalcoholic fatty liver disease and increases hepatic resistin and toll‐like receptor activation

Christian L. Roth, Clinton T. Elfers, Dianne P. Figlewicz, Susan J. Melhorn, Gregory J. Morton, Andrew Hoofnagle, Matthew M. Yeh, James E. Nelson, Kris V. Kowdley – 12 October 2011 – Childhood obesity is associated with type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). Recent studies have found associations between vitamin D deficiency (VDD), insulin resistance (IR), and NAFLD among overweight children.

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