Natural killer cell function is intact after direct exposure to infectious hepatitis C virions

Joo Chun Yoon, Masaaki Shiina, Golo Ahlenstiel, Barbara Rehermann – 28 December 2008 – Although hepatitis C virus (HCV) has been shown to readily escape from virus‐specific T and B cell responses, its effects on natural killer (NK) cells are less clear. Based on two previous reports that recombinant, truncated HCV E2 protein inhibits NK cell functions via crosslinking of CD81, it is now widely believed that HCV impairs NK cells as a means to establish persistence. However, the relevance of these findings has not been verified with HCV E2 expressed as part of intact virions.

Lymphotoxin‐β receptor signaling regulates hepatic stellate cell function and wound healing in a murine model of chronic liver injury

Richard G. Ruddell, Belinda Knight, Janina E. E. Tirnitz‐Parker, Barbara Akhurst, Lesa Summerville, V. Nathan Subramaniam, John K. Olynyk, Grant A. Ramm – 28 December 2008 – Lymphotoxin‐beta (LTβ) is a proinflammatory cytokine and a member of the tumor necrosis factor (TNF) superfamily known for its role in mediating lymph node development and homeostasis. Our recent studies suggest a role for LTβ in mediating the pathogenesis of human chronic liver disease. We hypothesize that LTβ co‐ordinates the wound healing response in liver injury via direct effects on hepatic stellate cells.

Differential mechanisms in the pathogenesis of autoimmune cholangitis versus inflammatory bowel disease in interleukin‐2Rα−/− mice

Willy Hsu, Weici Zhang, Koichi Tsuneyama, Yuki Moritoki, William M. Ridgway, Aftab A. Ansari, Ross L. Coppel, Zhe‐Xiong Lian, Ian Mackay, M. Eric Gershwin – 28 December 2008 – Interleukin‐2 (IL‐2) receptor α knockout (IL‐2Rα−/−) mice have a deficiency of CD25 and a corresponding functional defect in T regulatory cells (Tregs). These mice spontaneously develop portal inflammation with biliary ductular damage and colitis with features similar to human inflammatory bowel disease with T cell infiltrates in both the liver and colon.

Hepatic irradiation augments engraftment of donor cells following hepatocyte transplantation

Kosho Yamanouchi, Hongchao Zhou, Namita Roy‐Chowdhury, Frank Macaluso, Liping Liu, Toshiyuki Yamamoto, Govardhana Rao Yannam, Charles Enke, Timothy D. Solberg, Anthony B. Adelson, Jeffrey L. Platt, Ira J. Fox, Jayanta Roy‐Chowdhury, Chandan Guha – 28 December 2008 – Engraftment of donor hepatocytes is a critical step that determines the success of hepatocyte transplantation. Rapid and efficient integration of donor cells would enable prompt liver repopulation of these cells in response to selective proliferative stimuli offered by a preparative regimen.

Llama‐derived single‐domain intrabodies inhibit secretion of hepatitis B virions in mice

Benedikte Serruys, Freya Van Houtte, Phebe Verbrugghe, Geert Leroux‐Roels, Peter Vanlandschoot – 28 December 2008 – Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single‐domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV.

Randomized trial comparing pegylated interferon α‐2b versus pegylated interferon α‐2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients

Montserrat Laguno, Carmen Cifuentes, Javier Murillas, Sergio Veloso, Maria Larrousse, Antoni Payeras, Lucia Bonet, Francese Vidal, Ana Milinkovic, Antoni Bassa, Concha Villalonga, Iñaki Pérez, Cristina Tural, Maria Martínez‐Rebollar, Marta Calvo, Jose Luis Blanco, Estaban Martínez, Jose M. Sánchez‐Tapias, Jose M. Gatell, Jose Mallolas – 28 December 2008 – Although two pegylated interferons (Peg‐IFN) are available to treat chronic hepatitis C virus (HCV) infection, no head‐to‐head comparative studies have been published.

Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial

Stephen A. Harrison, Will Fecht, Elizabeth M. Brunt, Brent A. Neuschwander‐Tetri – 28 December 2008 – The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index = ≥27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks.

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