Mechanistic link between the anti‐HCV effect of interferon gamma and control of viral replication by a ras‐MAPK signaling cascade

Ying Huang, Xinyi Cynthia Chen, Madhavi Konduri, Nadejda Fomina, Jin Lu, Ling Jin, Alexander Kolykhalov, Seng‐Lai Tan – 22 December 2005 – Interferon‐gamma (IFN‐γ) exerts potent antiviral activity in the hepatitis C virus (HCV) replicon systems. However, the mechanisms underlying the direct antiviral effect have not been determined. We found that the type II transcriptional response to IFN‐γ could be suppressed by inhibition of MEK1/2 kinase activity by MEK1/2 inhibitor U0126 in the hepatoma cell line Huh‐7.

LPS inhibits endothelin‐1–induced endothelial NOS activation in hepatic sinusoidal cells through a negative feedback involving caveolin‐1

Walid S. Kamoun, Amel Karaa, Nicole Kresge, Sandra M. Merkel, Katarzyna Korneszczuk, Mark G. Clemens – 22 December 2005 – During endotoxemia, liver microcirculation disruption is characterized by a hypersensitivity to the constrictor effects of endothelin 1 (ET‐1). The shift of ET‐1–mediated effects toward vasoconstriction may result from depressed ET‐1–mediated vasodilation through decreased ET‐1–induced nitric oxide (NO) production.

Brain metabolism of 13N‐ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography

Susanne Keiding, Michael Sørensen, Dirk Bender, Ole Lajord Munk, Peter Ott, Hendrik Vilstrup – 22 December 2005 – Animal studies and results from 13N‐ammonia positron emission tomography (PET) in patients with cirrhosis and minimal hepatic encephalopathy suggest that a disturbed brain ammonia metabolism plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE).

Development and validation of two models for early prediction of response to therapy in genotype 1 chronic hepatitis C

Eva Martínez‐Bauer, Javier Crespo, Manuel Romero‐Gómez, Ricardo Moreno‐Otero, Ricard Solá, Nancy Tesei, Fernando Pons, Xavier Forns, José M. Sánchez‐Tapias – 22 December 2005 – Early prediction of response to therapy in genotype 1 chronic hepatitis C is difficult. Two predictive models, a pretreatment scoring model (PreT‐SM) and a fourth week of therapy scoring model (4w‐SM) were constructed in a cohort of 104 patients from a single center (estimation cohort) and validated in a cohort of 141 patients from four independent centers (validation cohort).

Limitation of combination therapy of interferon and ribavirin for older patients with chronic hepatitis C

Yoshiaki Iwasaki, Hiroshi Ikeda, Yasuyuki Araki, Toshiya Osawa, Keiji Kita, Masaharu Ando, Toshinari Shimoe, Kouichi Takaguchi, Noriaki Hashimoto, Toshitsugu Kobatake, Minoru Tomita, Mitsuhiko Kawaguchi, Haruhiko Kobashi, Kohsaku Sakaguchi, Yasushi Shiratori – 22 December 2005 – In contrast to the United States, Japanese patients with chronic hepatitis C currently treated with interferon are generally 10 to 15 years older. Older patients, however, tend to experience more frequent adverse events.

Systemic hemodynamics, vasoactive systems, and plasma volume in patients with severe Budd‐Chiari syndrome

Manuel Hernández‐Guerra, Eric López, Pablo Bellot, Carlos Piera, Juan Turnes, Juan G. Abraldes, Jaime Bosch, Juan C. García‐Pagán – 22 December 2005 – Budd‐Chiari syndrome (BCS) causes postsinusoidal portal hypertension, which leads to complications similar to those observed in cirrhosis. However, no studies have investigated whether patients with BCS develop the hyperdynamic circulatory syndrome present in patients with cirrhosis who have portal hypertension.

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