Dysfunction and functional restoration of HCV‐specific CD8 responses in chronic hepatitis C virus infection

Amalia Penna, Massimo Pilli, Alessandro Zerbini, Alessandra Orlandini, Sergio Mezzadri, Luca Sacchelli, Gabriele Missale, Carlo Ferrari – 26 February 2007 – The functional impairment of HCV‐specific T cell responses is believed to be an important determinant of HCV persistence, but the functional T cell defects of patients with chronic hepatitis C (CH‐C) are only partially defined. CD8 responses to HLA‐A2–restricted epitopes of HCV and other unrelated viruses were studied in 23 HLA‐A2–positive patients both ex vivo and after in vitro culture.

Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis

Luca Di Tommaso, Giada Franchi, Young Nyun Park, Barbara Fiamengo, Annarita Destro, Emanuela Morenghi, Marco Montorsi, Guido Torzilli, Maurizio Tommasini, Luigi Terracciano, Luigi Tornillo, Raffaella Vecchione, Massimo Roncalli – 26 February 2007 – Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC‐G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC‐G1 are involved.

Lactulose improves cognitive functions and health‐related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy

Srinivasa Prasad, Radha K. Dhiman, Ajay Duseja, Yogesh K. Chawla, Arpita Sharma, Ritesh Agarwal – 26 February 2007 – Minimal hepatic encephalopathy (MHE) has a negative effect on patients' daily functioning. Thus far, no study has investigated the effect of treatment‐related improvement in cognitive functions on health‐related quality of life (HRQOL).

MELD score as a predictor of liver failure and death in patients with acetaminophen‐induced liver injury

Lars E. Schmidt, Fin Stolze Larsen – 26 February 2007 – The Model for End‐Stage Liver Disease (MELD) scoring system has been established as a reliable measure of short‐term mortality risk in patients with end‐stage chronic liver disease. The aim of this study was to evaluate the prognostic value of the MELD scoring as a predictor of fulminant hepatic failure (FHF) and death in patients with acetaminophen poisoning. Prospectively, serial measurements of the 3 MELD components—INR, bilirubin, and creatinine—were performed in 460 patients with acetaminophen‐induced liver injury.

Impairment of hepatic Stat‐3 activation and reduction of PPARα activity in fructose‐fed rats

Núria Roglans, Laia Vilà, Mireia Farré, Marta Alegret, Rosa María Sánchez, Manuel Vázquez‐Carrera, Juan Carlos Laguna – 26 February 2007 – Fructose makes up a significant proportion of energy intake in westernized diets; its increased consumption has paralleled the growing prevalence of obesity and metabolic syndrome over the past two decades. In the current study, we demonstrate that fructose administration (10% wt/vol) in the drinking water of rats reduces the trans‐activating and trans‐repressing activity of the hepatic peroxisome proliferator‐activated receptor α (PPARα).

Prevention of hepatocyte allograft rejection in rats by transferring adenoviral early region 3 genes into donor cells

Elena V. Mashalova, Chandan Guha, Namita Roy‐Chowdhury, Laibin Liu, Ira J. Fox, Jayanta Roy‐Chowdhury, Marshall S. Horwitz – 26 February 2007 – Hepatocyte transplantation is being evaluated as an alternative to liver transplantation for metabolic support during liver failure and for definitive treatment of inherited liver diseases. However, as with liver transplantation, transplantation of allogeneic hepatocytes requires prolonged immunosuppression with its associated untoward effects.

Novel aspects of PPARα‐mediated regulation of lipid and xenobiotic metabolism revealed through a nutrigenomic study

Pascal G. P. Martin, Hervé Guillou, Frédéric Lasserre, Sébastien Déjean, Annaig Lan, Jean‐Marc Pascussi, Magali SanCristobal, Philippe Legrand, Philippe Besse, Thierry Pineau – 26 February 2007 – Peroxisome proliferator‐activated receptor‐α (PPARα) is a major transcriptional regulator of lipid metabolism. It is activated by diverse chemicals such as fatty acids (FAs) and regulates the expression of numerous genes in organs displaying high FA catabolic rates, including the liver.

The G‐protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells

Verena Keitel, Roland Reinehr, Petros Gatsios, Claudia Rupprecht, Boris Görg, Oliver Selbach, Dieter Häussinger, Ralf Kubitz – 26 February 2007 – Sinusoidal endothelial cells (SEC) constitute a permeable barrier between hepatocytes and blood. SEC are exposed to high concentrations of bile salts from the enterohepatic circulation. Whether SEC are responsive to bile salts is unknown. TGR5, a G‐protein–coupled bile acid receptor, which triggers cAMP formation, has been discovered recently in macrophages.

The model for end‐stage liver disease (MELD)

Patrick S. Kamath, W. Ray Kim – 26 February 2007 – The Model for End‐stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation.

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