p75 neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis

Timothy J. Kendall, Selina Hennedige, Rebecca L. Aucott, Stephen N. Hartland, Madeleine A. Vernon, R. Christopher Benyon, John P. Iredale – 24 February 2009 – Hepatic myofibroblast apoptosis is critical to resolution of liver fibrosis. We show that human hepatic myofibroblasts co‐express p75NTR (p75 neurotrophin receptor) and sortilin, thus facilitating differential responses to mature and pro nerve growth factor (proNGF). Although mature NGF is proapoptotic, proNGF protects human hepatic myofibroblasts from apoptosis.

Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: A 5‐year follow‐up of 150 patients

Sarah L. George, Bruce R. Bacon, Elizabeth M. Brunt, Kusal L. Mihindukulasuriya, Joyce Hoffmann, Adrian M. Di Bisceglie – 24 February 2009 – One hundred fifty patients with sustained virologic response (SVR) after treatment of chronic hepatitis C were enrolled in a long‐term clinical follow‐up study; patients were followed for 5 years for liver‐related outcomes and evidence of biochemical or virologic relapse. Patients with stage 2 or greater fibrosis on pretreatment biopsy were invited to undergo a long‐term follow‐up biopsy after their fourth year of follow‐up.

Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the scientific registry of transplant recipients database

Christian Toso, Sonal Asthana, David L. Bigam, A. M. James Shapiro, Norman M. Kneteman – 24 February 2009 – The current model of liver graft allocation in place in the United States favors transplantation of patients with small hepatocellular carcinomas (HCCs) within the Milan criteria (a single tumor up to 5 cm in diameter or up to three lesions, none larger than 3 cm). Although several reports have suggested that these criteria could be extended, there is currently no agreement on new selection tools.

Ethnic differences in hepatic steatosis: An insulin resistance paradox?

Richard Guerrero, Gloria L. Vega, Scott M. Grundy, Jeffrey D. Browning – 24 February 2009 – Nonalcoholic fatty liver disease is a burgeoning problem. We have previously shown that Hispanics were at greater risk for nonalcoholic fatty liver disease than were African‐Americans despite a similar prevalence of risk factors between these groups.

Ferritin functions as a proinflammatory cytokine via iron‐independent protein kinase C zeta/nuclear factor kappaB–regulated signaling in rat hepatic stellate cells

Richard G. Ruddell, Diem Hoang‐Le, Joanne M. Barwood, Paul S. Rutherford, Terrance J. Piva, Dianne J. Watters, Paolo Santambrogio, Paolo Arosio, Grant A. Ramm – 24 February 2009 – Circulating ferritin levels reflect body iron stores and are elevated with inflammation in chronic liver injury. H‐ferritin exhibits a number of extrahepatic immunomodulatory properties, although its role in hepatic inflammation and fibrogenesis is unknown. Hepatic stellate cells respond to liver injury through production of proinflammatory mediators that drive fibrogenesis.

Sustained virological response reduces incidence of onset of type 2 diabetes in chronic hepatitis C

Yasuji Arase, Fumitaka Suzuki, Yoshiyuki Suzuki, Norio Akuta, Masahiro Kobayashi, Yusuke Kawamura, Hiromi Yatsuji, Hitomi Sezaki, Tetsuya Hosaka, Miharu Hirakawa, Kenji Ikeda, Hiromitsu Kumada – 24 February 2009 – Diabetes is present in patients with chronic hepatitis C virus infection. The aim of this retrospective cohort study was to assess the cumulative development incidence and predictive factors for type 2 diabetes after the termination of interferon therapy in Japanese patients positive for hepatitis C virus (HCV).

Multiple division cycles and long‐term survival of hepatocytes are distinctly regulated by extracellular signal‐regulated kinases ERK1 and ERK2

Christophe Frémin, Anne Bessard, Frédéric Ezan, Luc Gailhouste, Morgane Régeard, Jacques Le Seyec, David Gilot, Gilles Pagès, Jacques Pouysségur, Sophie Langouët, Georges Baffet – 24 February 2009 – We investigated the specific role of the mitogen‐activated protein kinase (MAPK) extracellular signal‐regulated kinase 1 (ERK1)/ERK2 pathway in the regulation of multiple cell cycles and long‐term survival of normal hepatocytes. An early and sustained epidermal growth factor (EGF)‐dependent MAPK activation greatly improved the potential of cell proliferation.

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