Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir

Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Hitomi Sezaki, Miharu Hirakawa, Yusuke Kawamura, Tetsuya Hosaka, Masahiro Kobayashi, Satoshi Saito, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Kazuaki Chayama, Naoyuki Kamatani, Yusuke Nakamura, Yuzo Miyakawa, Hiromitsu Kumada – 29 October 2010 – Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG‐IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG‐IFN, RBV, and telaprevir are not known.

The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B negatively regulate cell proliferation through the activation of cyclin‐dependent kinase inhibitor 2b (Cdkn2b) and Cdkn1a expression

Ji Hoon Yu, Bing‐Mei Zhu, Mark Wickre, Gregory Riedlinger, Weiping Chen, Atsushi Hosui, Gertraud W. Robinson, Lothar Hennighausen – 29 October 2010 – Although the cytokine‐inducible transcription factor signal transducer and activator of transcription 5 (STAT5) promotes proliferation of a wide range of cell types, there are cell‐specific and context‐specific cases in which loss of STAT5 results in enhanced cell proliferation.

The fractalkine receptor CX3CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes

Karlin Raja Karlmark, Henning W. Zimmermann, Christoph Roderburg, Nikolaus Gassler, Hermann E. Wasmuth, Tom Luedde, Christian Trautwein, Frank Tacke – 29 October 2010 – Chemokines modulate inflammatory responses that are prerequisites for organ fibrosis upon liver injury. Monocyte‐derived hepatic macrophages are critical for the development, maintenance, and resolution of hepatic fibrosis.

Association of anti‐E1E2 antibodies with spontaneous recovery or sustained viral response to therapy in patients infected with hepatitis C virus

Ndiémé Ndongo, Pascale Berthillon, Pierre Pradat, Claude Vieux, Isabelle Bordes, Françoise Berby, Marianne Maynard, Fabien Zoulim, Christian Trépo, Marie‐Anne Petit – 29 October 2010 – The monoclonal antibody (mAb) D32.10 recognizes a discontinuous epitope encompassing three regions E1 (amino acids 297‐306), E2A (amino acids 480‐494), and E2B (amino acids 613‐621) juxtaposed on the surface of serum‐derived hepatitis C virus (HCV) particles (HCVsp). The mAb D32.10 inhibits efficiently and specifically the binding of HCVsp to human hepatocytes.

Anti–tumor necrosis factor α treatment promotes apoptosis and prevents liver regeneration in a transgenic mouse model of chronic hepatitis C

Erwin Daniel Brenndörfer, Malin Weiland, Lars Frelin, Emma Derk, Gustaf Ahlén, Jian Jiao, Johannes Georg Bode, Matti Sällberg – 29 October 2010 – Tumor necrosis factor α (TNFα) has been implicated in a variety of inflammatory diseases, and anti‐TNFα has been shown to improve therapy when added to standard of care in chronic hepatitis C virus (HCV) infection. In addition, patients with chronic HCV have increased serum levels of TNFα and the macrophage‐attracting chemokine (C‐C motif) ligand 2 (CCL2).

A phase 1/2, dose‐escalation trial of deferasirox for the treatment of iron overload in HFE‐related hereditary hemochromatosis

Pradyumna Phatak, Pierre Brissot, Mark Wurster, Paul C Adams, Herbert L. Bonkovsky, John Gross, Peter Malfertheiner, Gordon D. McLaren, Claus Niederau, Alberto Piperno, Lawrie W. Powell, Mark W. Russo, Ulrich Stoelzel, Wolfgang Stremmel, Louis Griffel, Nicola Lynch, Yiyun Zhang, Antonello Pietrangelo – 29 October 2010 – Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload.

Hyponatremia in patients treated with terlipressin for severe gastrointestinal bleeding due to portal hypertension

Elsa Solà, Sabela Lens, Mónica Guevara, Marta Martín‐Llahí, Claudia Fagundes, Gustavo Pereira, Marco Pavesi, Javier Fernández, Juan González‐Abraldes, Angels Escorsell, Antoni Mas, Jaume Bosch, Vicente Arroyo, Pere Ginès – 29 October 2010 – Terlipressin is frequently used in acute variceal bleeding due to its powerful effect on vasopressin V1 receptors. Although terlipressin is also a partial agonist of renal vasopressin V2 receptors, its effects on serum sodium concentration have not been specifically investigated.

Interferon regulatory factor 3 and type I interferons are protective in alcoholic liver injury in mice by way of crosstalk of parenchymal and myeloid cells

Jan Petrasek, Angela Dolganiuc, Timea Csak, Bharath Nath, Istvan Hritz, Karen Kodys, Donna Catalano, Evelyn Kurt‐Jones, Pranoti Mandrekar, Gyongyi Szabo – 29 October 2010 – Alcoholic liver disease (ALD) features increased hepatic exposure to bacterial lipopolysaccharide (LPS). Toll‐like receptor‐4 (TLR4) recognizes LPS and activates signaling pathways depending on MyD88 or TRIF adaptors. We previously showed that MyD88 is dispensable in ALD. TLR4 induces Type I interferons (IFNs) in an MyD88‐independent manner that involves interferon regulatory factor‐3 (IRF3).

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