Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus–infected patients

Simone Susser, Christoph Welsch, Yalan Wang, Markus Zettler, Francisco S. Domingues, Ursula Karey, Eric Hughes, Robert Ralston, Xiao Tong, Eva Herrmann, Stefan Zeuzem, Christoph Sarrazin – 20 November 2009 – Boceprevir is a hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor that is currently being evaluated in combination with peginterferon alfa‐2b and ribavirin in phase 3 studies. The clinical resistance profile of boceprevir is not characterized in detail so far. The NS3 protease domain of viral RNA was cloned from HCV genotype 1–infected patients (n = 22).

Reduced expression of ATP7B affected by Wilson disease–causing mutations is rescued by pharmacological folding chaperones 4‐phenylbutyrate and curcumin

Peter V. E. van den Berghe, Janneke M. Stapelbroek, Elmar Krieger, Prim de Bie, Stan F. J. van de Graaf, Reinoud E. A. de Groot, Ellen van Beurden, Ellen Spijker, Roderick H. J. Houwen, Ruud Berger, Leo W. J. Klomp – 20 November 2009 – Wilson disease (WD) is an autosomal recessive copper overload disorder of the liver and basal ganglia. WD is caused by mutations in the gene encoding ATP7B, a protein localized to the trans‐Golgi network that primarily facilitates hepatic copper excretion.

Ikappa B kinaseβ/nuclear factor‐κB activation controls the development of liver metastasis by way of interleukin‐6 expression

Shin Maeda, Yohko Hikiba, Kei Sakamoto, Hayato Nakagawa, Yoshihiro Hirata, Yoku Hayakawa, Ayako Yanai, Keiji Ogura, Michael Karin, Masao Omata – 20 November 2009 – Nuclear factor kappaB (NF‐κB) plays an important role in the regulation of innate immune responses, apoptosis, inflammation, and oncogenesis. NF‐κB activation in the liver was observed after intrasplenic administration of a lung carcinoma cell line, LLC, which induces liver metastasis.

Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload

Daniel F. Wallace, Lesa Summerville, Emily M. Crampton, David M. Frazer, Gregory J. Anderson, V. Nathan Subramaniam – 20 November 2009 – Hepcidin is a central regulator of iron homeostasis. HFE and transferrin receptor 2 (TFR2) are mutated in adult‐onset forms of hereditary hemochromatosis and regulate the expression of hepcidin in response to iron. Whether they act through the same or parallel pathways is unclear. To investigate this, we generated a mouse model with deletion of both Hfe and Tfr2 genes by crossing Hfe and Tfr2 null mice on a genetically identical background.

Severe lactic acidosis during treatment of chronic hepatitis B with entecavir in patients with impaired liver function

Christian M. Lange, Jörg Bojunga, Wolf Peter Hofmann, Katrin Wunder, Ulrike Mihm, Stefan Zeuzem, Christoph Sarrazin – 20 November 2009 – Entecavir is a potent nucleoside inhibitor of the hepatitis B virus (HBV) polymerase with a high antiviral efficacy and a high genetic barrier to viral resistance. After approval in 2006, knowledge on the side effect profile in patients with advanced liver disease and impaired liver function is still limited. Here, we report on 16 patients with liver cirrhosis and chronic hepatitis B who were treated with entecavir.

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