Neutrophils aggravate acute liver injury during obstructive cholestasis in bile duct–ligated mice

Jaspreet S. Gujral, Anwar Farhood, Mary Lynn Bajt, Hartmut Jaeschke – 30 December 2003 – Obstruction of the common bile duct in a variety of clinical settings leads to cholestatic liver injury. An important aspect of this injury is hepatic inflammation, with neutrophils as the prominent cell type involved. However, the pathophysiologic role of the infiltrating neutrophils during cholestatic liver injury remains unclear.

A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C

Chun‐Tao Wai, Joel K. Greenson, Robert J. Fontana, John D. Kalbfleisch, Jorge A. Marrero, Hari S. Conjeevaram, Anna S.‐F. Lok – 30 December 2003 – Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC.

Modulation of the outcome and severity of hepadnaviral hepatitis in woodchucks by antibodies to hepatic asialoglycoprotein receptor

Jingyu Diao, Darlene M. Slaney, Tomasz I. Michalak – 30 December 2003 – Viral hepatitis is frequently accompanied by humoral autoimmune responses toward both organ‐nonspecific and liver‐specific antigens, but contribution of these reactivities to liver injury remains unrecognized. Infection with woodchuck hepatitis virus (WHV) has been identified as a potent inducer of autoantibodies against asialoglycoprotein receptor (anti‐ASGPR), a molecule essentially unique to hepatocytes that mediates clearance of desialylated serum proteins.

Cyclooxygenase‐2 promotes hepatocellular carcinoma cell growth through AKT activation: Evidence for AKT inhibition in celecoxib‐induced apoptosis

Jing Leng, Chang Han, A. Jake Demetris, George K. Michalopoulos, Tong Wu – 30 December 2003 – Cyclooxygenase‐2 (COX‐2)‐controlled prostaglandin (PG) metabolism recently has been implicated in the pathogenesis of hepatocellular carcinoma (HCC). However, the biologic role and molecular mechanism of COX‐2‐mediated PGs in the control of liver cancer growth have not been established. This study was designed to examine the direct effect of COX‐2 and its inhibitor celecoxib on the growth control of liver cancer cells.

Establishment, characterization, and long‐term maintenance of cultures of human fetal hepatocytes

Catherine A. Lázaro, Emma J. Croager, Claudia Mitchell, Jean S. Campbell, Changpu Yu, Jessica Foraker, Jonathan A. Rhim, George C. T. Yeoh, Nelson Fausto – 30 December 2003 – Cultured human hepatocytes have broad research and clinical applications; however, the difficulties in culturing rodent and human hepatocytes are well known. These problems include the rapid loss of the hepatocytic phenotype in primary culture and the limited replicating capacity of the cultured cells.

Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression

Ali Canbay, Ariel E. Feldstein, Hajime Higuchi, Nate Werneburg, Annette Grambihler, Steve F. Bronk, Gregory J. Gores – 30 December 2003 – Hepatocyte apoptosis by death receptors, hepatic inflammation, and fibrosis are prominent features of liver diseases. However, the link between these processes remains unclear. Our aim was to ascertain whether engulfment of apoptotic bodies by Kupffer cells promotes hepatic inflammation and fibrosis. Isolated murine Kupffer cells efficiently engulfed apoptotic bodies generated from UV‐treated mouse hepatocytes.

Deficiency in virion secretion and decreased stability of the hepatitis B virus immune escape mutant G145R

Tatyana Kalinina, Alicja Iwanski, Hans Will, Martina Sterneck – 30 December 2003 – Hepatitis B virus with a G145R mutation in the small surface protein is considered the quintessential immune escape mutant because it frequently is found in vaccinated individuals with breakthrough infections and liver transplant recipients under anti‐hepatitis B surface antigen (HBsAg) immunoglobulin prophylaxis. Nowadays the prevalence of the variant progressively increases.

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