Hepatic macrophage migration and differentiation critical for liver fibrosis is mediated by the chemokine receptor C‐C motif chemokine receptor 8 in mice

Felix Heymann, Linda Hammerich, Dunja Storch, Matthias Bartneck, Sebastian Huss, Vanessa Rüsseler, Nikolaus Gassler, Sergio A. Lira, Tom Luedde, Christian Trautwein, Frank Tacke – 26 October 2011 – Chemokines critically control the infiltration of immune cells upon liver injury, thereby promoting hepatic inflammation and fibrosis. The chemokine receptor CCR8 can affect trafficking of monocytes/macrophages, monocyte‐derived dendritic cells (DCs) and T‐helper cell (Th) subsets, but its role in liver diseases is currently unknown.

Receptor activator of nuclear factor‐κB ligand (RANKL) protects against hepatic ischemia/reperfusion injury in mice

Nozomu Sakai, Heather L. Van Sweringen, Rebecca Schuster, John Blanchard, Justin M. Burns, Amit D. Tevar, Michael J. Edwards, Alex B. Lentsch – 26 October 2011 – The transcription factor nuclear factor kappaB (NF‐κB) plays diverse roles in the acute injury response to hepatic ischemia/reperfusion (I/R). Activation of NF‐κB in Kupffer cells promotes inflammation through cytokine expression, whereas activation in hepatocytes may be cell protective.

Stem cells in liver diseases and cancer: Recent advances on the path to new therapies

C. Bart Rountree, Lopa Mishra, Holger Willenbring – 26 October 2011 – Stem cells have potential for therapy of liver diseases, but may also be involved in the formation of liver cancer. Recently, the American Association for the Study of Liver Diseases Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation.

β‐Catenin is essential for ethanol metabolism and protection against alcohol‐mediated liver steatosis in mice

Shiguang Liu, Tzu‐Hsuan Yeh, Vijay P. Singh, Sruti Shiva, Lindsay Krauland, Huanan Li, Pili Zhang, Kusum Kharbanda, Vladimir Ritov, Satdarshan P.S. Monga, Donald K. Scott, Patricia K. Eagon, Jaideep Behari – 26 October 2011 – The liver plays a central role in ethanol metabolism, and oxidative stress is implicated in alcohol‐mediated liver injury. β‐Catenin regulates hepatic metabolic zonation and adaptive response to oxidative stress. We hypothesized that β‐catenin regulates the hepatic response to ethanol ingestion.

Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation

Marc Lütgehetmann, Lida V. Mancke, Tassilo Volz, Martina Helbig, Lena Allweiss, Till Bornscheuer, Joerg M. Pollok, Ansgar W. Lohse, J. Petersen, Stephan Urban, Maura Dandri – 26 October 2011 – No specific drugs are currently available against hepatitis delta virus (HDV), a defective virus leading to the most severe form of chronic viral hepatitis in man. The lack of convenient HDV infection models has hampered the development of effective therapeutics.

Activation of chemokine and inflammatory cytokine response in hepatitis C virus–infected hepatocytes depends on toll‐like receptor 3 sensing of hepatitis C virus double‐stranded RNA intermediates

Kui Li, Nan L. Li, Dahai Wei, Susan R. Pfeffer, Meiyun Fan, Lawrence M. Pfeffer – 26 October 2011 – Chemokines and inflammatory cytokines are key regulators of immunity and inflammation during viral infections. Hepatitis C virus (HCV) is a hepatotropic RNA virus frequently associated with chronic liver inflammation and hepatocellular carcinoma. Intrahepatic levels of chemokines and cytokines are elevated in chronic HCV infections, but the underlying mechanisms remain unclear.

Hepatitis C virus reinfection and superinfection among treated and untreated participants with recent infection

Jason Grebely, Son Truong Pham, Gail V. Matthews, Kathy Petoumenos, Rowena A. Bull, Barbara Yeung, William Rawlinson, John Kaldor, Andrew Lloyd, Margaret Hellard, Gregory J. Dore, Peter A. White, on behalf of the ATAHC Study Group – 26 October 2011 – The purpose of the study was to evaluate reinfection and superinfection during treatment for recent hepatitis C virus (HCV). The Australian Trial in Acute Hepatitis C (ATAHC) was a prospective study of the natural history and treatment of recent HCV.

Human liver cell spheroids in extended perfusion bioreactor culture for repeated‐dose drug testing

Rui M. Tostões, Sofia B. Leite, Margarida Serra, Janne Jensen, Petter Björquist, Manuel J. T. Carrondo, Catarina Brito, Paula M. Alves – 26 October 2011 – Primary cultures of human hepatocyte spheroids are a promising in vitro model for long‐term studies of hepatic metabolism and cytotoxicity. The lack of robust methodologies to culture cell spheroids, as well as a poor characterization of human hepatocyte spheroid architecture and liver‐specific functionality, have hampered a widespread adoption of this three‐dimensional culture format.

Growth‐hormone–induced signal transducer and activator of transcription 5 signaling causes gigantism, inflammation, and premature death but protects mice from aggressive liver cancer

Katrin Friedbichler, Madeleine Themanns, Kristina M. Mueller, Michaela Schlederer, Jan‐Wilhelm Kornfeld, Luigi M. Terracciano, Andrey V. Kozlov, Susanne Haindl, Lukas Kenner, Thomas Kolbe, Mathias Mueller, Kenneth J. Snibson, Markus H. Heim, Richard Moriggl – 26 October 2011 – Persistently high levels of growth hormone (GH) can cause liver cancer. GH activates multiple signal‐transduction pathways, among them janus kinase (JAK) 2‐signal transducer and activator of transcription (STAT) 5 (signal transducer and activator of transcription 5).

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