B‐cell depletion with anti‐CD20 ameliorates autoimmune cholangitis but exacerbates colitis in transforming growth factor‐β receptor II dominant negative mice

Yuki Moritoki, Zhe‐Xiong Lian, Keith Lindor, Joseph Tuscano, Koichi Tsuneyama, Weici Zhang, Yoshiyuki Ueno, Robert Dunn, Marilyn Kehry, Ross L. Coppel, Ian R. Mackay, M. Eric Gershwin – 20 November 2009 – The treatment of primary biliary cirrhosis (PBC) with conventional immunosuppressive drugs has been relatively disappointing and there have been few efforts in defining a role for the newer biological agents useful in rheumatoid arthritis and other systemic autoimmune diseases.

Not interferon, but interleukin‐6 controls early gene expression in hepatitis B virus infection

Marianna Hösel, Maria Quasdorff, Katja Wiegmann, Dennis Webb, Uta Zedler, Mathias Broxtermann, Raindy Tedjokusumo, Knud Esser, Silke Arzberger, Carsten J. Kirschning, Anja Langenkamp, Christine Falk, Hildegard Büning, Stefan Rose‐John, Ulrike Protzer – 20 November 2009 – With about 350 million virus carriers, hepatitis B virus (HBV) infection remains a major health problem. HBV is a noncytopathic virus causing persistent infection, but it is still unknown whether host recognition of HBV may activate an innate immune response.

Sorafenib inhibits signal transducer and activator of transcription‐3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2

Boris R. A. Blechacz, Rory L. Smoot, Steven F. Bronk, Nathan W. Werneburg, Alphonse E. Sirica, Gregory J. Gores – 20 November 2009 – The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is one of the key signaling cascades in cholangiocarcinoma (CCA) cells, mediating their resistance to apoptosis. Our aim was to ascertain if sorafenib, a multikinase inhibitor, may also inhibit JAK/STAT signaling and, therefore, be efficacious for CCA. Sorafenib treatment of three human CCA cell lines resulted in Tyr705 phospho‐STAT3 dephosphorylation.

Maternal high‐fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression

Kimberley D. Bruce, Felino R. Cagampang, Marco Argenton, Junlong Zhang, Priya L. Ethirajan, Graham C. Burdge, Adrian C. Bateman, Geraldine F. Clough, Lucilla Poston, Mark A. Hanson, Josie M. McConnell, Christopher D. Byrne – 20 November 2009 – Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others.

Priming of CD4+ T cells by liver sinusoidal endothelial cells induces CD25low forkhead box protein 3− regulatory T cells suppressing autoimmune hepatitis

Nils Kruse, Katrin Neumann, Arnhild Schrage, Katja Derkow, Eckart Schott, Ulrike Erben, Anja Kühl, Christoph Loddenkemper, Martin Zeitz, Alf Hamann, Katja Klugewitz – 20 November 2009 – Elucidating cellular mechanisms that maintain the intrahepatic immune balance is crucial to our understanding of viral or autoimmune liver diseases and allograft acceptance.

Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis

Eiji Kakazu, Yoshiyuki Ueno, Yasuteru Kondo, Koji Fukushima, Masaaki Shiina, Jun Inoue, Keiichi Tamai, Masashi Ninomiya, Tooru Shimosegawa – 20 November 2009 – An imbalance of plasma amino acids is observed in patients with advanced cirrhosis. The aim of this study was to investigate the influence of the extracellular amino acid imbalance on the function of myeloid dendritic cells (DCs) in patients with advanced cirrhosis.

Activation of the complement system in human nonalcoholic fatty liver disease

Sander S. Rensen, Yanti Slaats, Ann Driessen, Carine J. Peutz‐Kootstra, Jeroen Nijhuis, Rudi Steffensen, Jan Willem Greve, Wim A. Buurman – 20 November 2009 – Activation of the innate immune system plays a major role in nonalcoholic fatty liver disease (NAFLD). The complement system is an important component of innate immunity that recognizes danger signals such as tissue injury.

Cyclin‐dependent kinase 1 plays a critical role in DNA replication control during rat liver regeneration

Delphine Garnier, Pascal Loyer, Catherine Ribault, Christiane Guguen‐Guillouzo, Anne Corlu – 20 November 2009 – Liver regeneration is a unique process to restore hepatic homeostasis through rapid and synchronous proliferation of differentiated hepatocytes. Previous studies have shown that hepatocyte proliferation is characterized by high expression levels of the “mitotic” cyclin‐dependent kinase 1 (Cdk1) during S‐phase compared to other mammalian cells.

Public health impact of antiviral therapy for hepatitis C in the United States

Michael L. Volk, Rachel Tocco, Sameer Saini, Anna S.F. Lok – 20 November 2009 – Despite dramatic improvements in antiviral therapy for hepatitis C, there is reason to believe that the uptake of antiviral therapy remains limited. The aims of this study were to determine the number of patients being treated with antiviral therapy in the U.S., to estimate the public health impact of these treatment patterns, and to identify barriers to treatment for patients with hepatitis C.

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