B cell depletion therapy exacerbates murine primary biliary cirrhosis

Amy Dhirapong, Ana Lleo, Guo‐Xiang Yang, Koichi Tsuneyama, Robert Dunn, Marilyn Kehry, Thomas A. Packard, John C. Cambier, Fu‐Tong Liu, Keith Lindor, Ross L. Coppel, Aftab A. Ansari, M. Eric Gershwin – 18 October 2010 – Primary biliary cirrhosis (PBC) is considered a model autoimmune disease due to the clinical homogeneity of patients and the classic hallmark of antimitochondrial antibodies (AMAs). Indeed, the presence of AMAs represents the most highly directed and specific autoantibody in autoimmune diseases. However, the contribution of B cells to the pathogenesis of PBC is unclear.

Autoantigen‐specific regulatory T cells, a potential tool for immune‐tolerance reconstitution in type‐2 autoimmune hepatitis

Maria Serena Longhi, Munther J. Hussain, William W. Kwok, Giorgina Mieli‐Vergani, Yun Ma, Diego Vergani – 18 October 2010 – Effector CD4 and CD8 T cell immune responses to cytochrome P450IID6 (CYP2D6), the autoantigen of autoimmune hepatitis type 2 (AIH‐2), are permitted by a numerical and functional impairment of CD4posCD25high regulatory T cells (T‐regs).

Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

Vlad Ratziu, Stephen Caldwell, Brent A. Neuschwander‐Tetri – 18 October 2010 – Insulin sensitizers are attractive candidate therapies for nonalcoholic steatohepatitis mainly because of the strong association between this disease and insulin resistance. This review provides a critical overview of the mechanisms of action, clinical trial results, and safety issues of metformin and glitazones in nonalcoholic steatohepatitis. It also highlights methodological challenges for trial design and proposes endpoints for future proof of principle, registrational, and postmarketing trials.

Activation of alpha1‐adrenergic receptors stimulate the growth of small mouse cholangiocytes Via calcium‐dependent activation of nuclear factor of activated T cells 2 and specificity protein 1

Gianfranco Alpini, Antonio Franchitto, Sharon DeMorrow, Paolo Onori, Eugenio Gaudio, Candace Wise, Heather Francis, Julie Venter, Shelley Kopriva, Romina Mancinelli, Guido Carpino, Franco Stagnitti, Yoshiyuki Ueno, Yuyan Han, Fanyin Meng, Shannon Glaser – 18 October 2010 – Small cholangiocytes proliferate via activation of calcium (Ca2+)‐dependent signaling in response to pathological conditions that trigger the damage of large cyclic adenosine monophosphate–dependent cholangiocytes.

Different biochemical correlates for different neuropsychiatric abnormalities in patients with cirrhosis

Sara Montagnese, Anna Biancardi, Sami Schiff, Paolo Carraro, Vincenzo Carlà, Guido Mannaioni, Flavio Moroni, Natascia Tono, Paolo Angeli, Angelo Gatta, Piero Amodio – 18 October 2010 – The diagnosis of hepatic encephalopathy (HE) relies on clinical, neurophysiological, psychometric and laboratory variables. The relationships between such tests remain debated. The aim of this study was to determine the laboratory correlates/prognostic value of neurophysiological/psychometric abnormalities in patients with cirrhosis.

Effect of sorafenib on murine liver regeneration

Caroline Hora, Pamela Romanque, Jean‐François F. Dufour – 11 October 2010 – Hepatocellular carcinoma (HCC) is a common cause of cancer‐related death. Sorafenib prolongs survival of patients with advanced disease and is approved for the systemic treatment of unresectable HCC. It possesses antiangiogenic and antiproliferative properties by way of inhibition of the receptor tyrosine kinases vascular endothelial growth factor receptor 2 (VEGFR‐2) and platelet‐derived growth factor receptor‐beta 1/2 (PDGFR‐β) and the kinase RAF.

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