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.

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.

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.

Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease

Sylvie Naveau, Guillaume Gaudé, Amani Asnacios, Hélène Agostini, Annie Abella, Nadège Barri‐Ova, Barbara Dauvois, Sophie Prévot, Yen Ngo, Mona Munteanu, Axel Balian, Micheline Njiké‐Nakseu, Gabriel Perlemuter, Thierry Poynard – 28 December 2008 – FibroTest has been validated as a biomarker of fibrosis in patients with chronic viral hepatitis, with a similar prognostic value as biopsy. The aim of the study was to compare the diagnostic and prognostic values of FibroTest versus the recently patented biomarkers, FibrometerA, and Hepascore.

Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population‐based study of U.S. veterans

Hashem B. El‐Serag, Eric A. Engels, Ola Landgren, Elizabeth Chiao, Louise Henderson, Harshinie C. Amaratunge, Thomas P. Giordano – 28 December 2008 – Hepatitis C virus (HCV) may increase the risk of hepatopancreaticobiliary tumors other than hepatocellular carcinoma (HCC). Previous case control studies indicated a possible association between HCV and intrahepatic cholangiocarcinoma (ICC). Little is known about the association between HCV and extrahepatic cholangiocarcinoma (ECC) or pancreatic cancer.

Atorvastatin prevents carbohydrate response element binding protein activation in the fructose‐fed rat by activating protein kinase A

Ricardo Rodríguez‐Calvo, Emma Barroso, Lucía Serrano, Teresa Coll, Rosa M. Sánchez, Manuel Merlos, Xavier Palomer, Juan C. Laguna, Manuel Vázquez‐Carrera – 28 December 2008 – High fructose intake contributes to the overall epidemic of obesity and metabolic disease. Here we examined whether atorvastatin treatment blocks the activation of the carbohydrate response element binding protein (ChREBP) in the fructose‐fed rat.

A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma

Daniel H. Palmer, Rachel S. Midgley, Noweeda Mirza, Elizabeth E. Torr, Forhad Ahmed, Jane C. Steele, Neil M. Steven, David J. Kerr, Lawrence S. Young, David H. Adams – 28 December 2008 – This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo with a liver tumor cell line lysate (HepG2) in patients with advanced hepatocellular carcinoma (HCC).

Competitive inhibition of leptin signaling results in amelioration of liver fibrosis through modulation of stellate cell function

Eran Elinav, Mohammad Ali, Rafi Bruck, Eli Brazowski, Adam Phillips, Yami Shapira, Meirav Katz, Gila Solomon, Zamir Halpern, Arieh Gertler – 28 December 2008 – Leptin signaling is involved in T‐cell polarization and is required for profibrotic function of hepatic stellate cells (HSCs). Leptin‐deficient ob/ob mice do not develop liver fibrosis despite the presence of severe long‐standing steatohepatitis.

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