Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha

Mitchell L. Shiffman, Jennifer Salvatore, Sarah Hubbard, Angie Price, Richard K. Sterling, R. Todd Stravitz, Velimir A. Luketic, Arun J. Sanyal – 27 July 2007 – Successful treatment of chronic HCV with peginterferon (PEGIFN) and ribavirin (RVN) is often limited by anemia. We performed the present study to determine if utilizing epoetin alpha (EPO) with or without a higher dose of RVN could enhance sustained virologic response (SVR).

Inflammation and hepatic encephalopathy: Ibuprofen restores learning ability in rats with portacaval shunts

Omar Cauli, Regina Rodrigo, Blanca Piedrafita, Jordi Boix, Vicente Felipo – 27 July 2007 – One of the neurological alterations in patients with minimal or overt hepatic encephalopathy is cognitive impairment. This impairment is reproduced in rats with chronic liver failure due to portacaval shunt (PCS). These rats show decreased ability to learn a conditional discrimination task in a Y‐maze, likely due to reduced function of the glutamate–nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in brain.

Profibrogenic transforming growth factor‐β/activin receptor–like kinase 5 signaling via connective tissue growth factor expression in hepatocytes

Hong‐Lei Weng, Loredana Ciuclan, Yan Liu, Jafar Hamzavi, Patricio Godoy, Haristi Gaitantzi, Stefan Kanzler, Rainer Heuchel, Uwe Ueberham, Rolf Gebhardt, Katja Breitkopf, Steven Dooley – 26 July 2007 – Connective tissue growth factor (CTGF) is important for transforming growth factor‐β (TGF‐β)–induced liver fibrogenesis. Hepatic stellate cells have been recognized as its major cellular source in the liver. Here we demonstrate the induction of CTGF expression in hepatocytes of damaged livers and identify a molecular mechanism responsible for it.

Overexpression and role of the ATPase and putative DNA helicase RuvB‐like 2 in human hepatocellular carcinoma

Benoît Rousseau, Ludovic Ménard, Valérie Haurie, Danièle Taras, Jean‐Frédéric Blanc, François Moreau‐Gaudry, Philippe Metzler, Michel Hugues, Sandrine Boyault, Sylvie Lemière, Xavier Canron, Pierre Costet, Michael Cole, Charles Balabaud, Paulette Bioulac‐Sage, Jessica Zucman‐Rossi, Jean Rosenbaum – 26 July 2007 – Using a proteomic analysis of human hepatocellular carcinoma (HCC), we identified the overexpression in 4 tumors of RuvB‐like 2 (RUVBL2), an ATPase and putative DNA helicase known to interact with β‐catenin and cellular v‐myc myelocytomatosis viral oncogene homolog (c‐myc).

Differential priming of CD8 and CD4 T‐cells in animal models of autoimmune hepatitis and cholangitis

Katja Derkow, Christoph Loddenkemper, Justine Mintern, Nils Kruse, Katja Klugewitz, Thomas Berg, Bertram Wiedenmann, Hidde L. Ploegh, Eckart Schott – 26 July 2007 – The pathogenesis of autoimmune liver diseases is poorly understood. Animal models are necessary to investigate antigen presentation and priming of T‐cells in the context of autoimmunity in the liver. Transgenic mouse models were generated in which the model antigen ovalbumin is expressed in hepatocytes (TF‐OVA) or cholangiocytes (ASBT‐OVA).

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

Yen‐Shen Lu, Yoko Kashida, Samuel K. Kulp, Yu‐Chieh Wang, Dasheng Wang, Jui‐Hsiang Hung, Monica Tang, Zhong‐Zhe Lin, Te‐Jung Chen, Ann‐Lii Cheng, Ching‐Shih Chen – 25 July 2007 – Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, yet effective therapeutic options for advanced HCC are limited. This study was aimed at assessing the antitumor effect of a novel phenylbutyrate‐derived histone deacetylase (HDAC) inhibitor, OSU‐HDAC42, vis‐à‐vis suberoylanilide hydroxamic acid (SAHA), in in vitro and in vivo models of human HCC.

Role of the coagulation system in acetaminophen‐induced hepatotoxicity in mice

Patricia E. Ganey, James P. Luyendyk, Sandra W. Newport, Theresa M. Eagle, Jane F. Maddox, Nigel Mackman, Robert A. Roth – 25 July 2007 – Acetaminophen (N‐acetyl‐p‐aminophenol [APAP]) is one of the leading causes of acute liver failure, and APAP hepatotoxicity is associated with coagulopathy in humans. We tested the hypothesis that activation of the coagulation system and downstream protease‐activated receptor (PAR)‐1 signaling contribute to APAP‐induced liver injury.

Hepatitis B virus DNA prediction rules for hepatitis B e antigen–negative chronic hepatitis B

Jordan J. Feld, Melissa Ayers, Dahlia El‐Ashry, Tony Mazzulli, Raymond Tellier, E. Jenny Heathcote – 25 July 2007 – After hepatitis B e antigen (HBeAg) seroconversion, hepatitis B may become inactive or progress to HBeAg‐negative hepatitis with persistent or intermittent alanine aminotransferase (ALT) elevation. The aim of this study was to prospectively identify factors predictive of the clinical course in HBeAg‐negative chronic hepatitis B (CHB). Patients were stratified by ALT and HBeAg status and followed every 3 months for up to 5 years.

A lipidomic analysis of nonalcoholic fatty liver disease

Puneet Puri, Rebecca A. Baillie, Michelle M. Wiest, Faridoddin Mirshahi, Jayanta Choudhury, Onpan Cheung, Carol Sargeant, Melissa J. Contos, Arun J. Sanyal – 25 July 2007 – The spectrum of nonalcoholic fatty liver disease (NAFLD) includes a nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The specific types and amounts of lipids that accumulate in NAFLD are not fully defined.

Fractures and avascular necrosis before and after orthotopic liver transplantation: Long‐term follow‐up and predictive factors

Maureen M. J. Guichelaar, Jeffrey Schmoll, Michael Malinchoc, J. Eileen Hay – 25 July 2007 – With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications.

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