Autoimmune regulator AIRE: Evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1

Arndt Vogel, Heike Liermann, Andrea Harms, Christian P. Strassburg, Michael P. Manns, Petra Obermayer‐Straub – 30 December 2003 – The mechanisms driving the immune‐mediated destruction of hepatic tissues in autoimmune hepatitis (AIH) are unknown. Recently the autoimmune regulator (AIRE), a gene associated with the development of the autoimmune polyglandular syndrome type 1 (APS‐1), was cloned. About 15% to 20% of APS‐1 patients develop hepatitis. However, the role of AIRE mutations in AIH, primary sclerosing cholangitis (PSC), and primary biliary cirrhosis (PBC) is not known.

Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi

Junichi Shoda, Koji Oda, Hiroshi Suzuki, Yuichi Sugiyama, Kosei Ito, David E. Cohen, Li Feng, Junichi Kamiya, Yuji Nimura, Hiroshi Miyazaki, Masahito Kano, Yasushi Matsuzaki, Naomi Tanaka – 30 December 2003 – Intrahepatic calculi, highly prevalent in the Far East, including Japan, are characterized clinically by chronic proliferative cholangitis with frequent stone recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment stones, including a high cholesterol content, and cholesterol stones, with the former predominating.

Hepatitis B infection in patients with acute liver failure in the United States

Eng‐Kiong Teo, George Ostapowicz, Munira Hussain, William M. Lee, Robert J. Fontana, Anna S. F. Lok – 30 December 2003 – Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B.

Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non–iron‐related chronic liver disease

Anna Ludovica Fracanzani, Dario Conte, Mirella Fraquelli, Emanuela Taioli, Michela Mattioli, Alessandra Losco, Silvia Fargion – 30 December 2003 – It has been suggested that excess iron may facilitate the occurrence of cancer. Patients with hereditary hemochromatosis (HH) are at high risk of developing liver cancer, and studies of limited series reported a high frequency of nonhepatic cancers.

Mechanism of cell death during warm hepatic ischemia‐reperfusion in rats: Apoptosis or necrosis?

Jaspreet S. Gujral, Thomas J. Bucci, Anwar Farhood, Hartmut Jaeschke – 30 December 2003 – Reperfusion injury can cause liver dysfunction after cold storage and warm ischemia. Recently it has been suggested that more than 50% of hepatocytes and sinusoidal endothelial cells (SEC) are undergoing apoptosis during the first 24 hours of reperfusion. The aim of our study was to quantify apoptotic and necrotic hepatocytes and apoptotic SEC after 60 or 120 minutes of warm, partial no‐flow ischemia and 0 to 24 hours reperfusion in male SD rats.

DNA prime/canarypox boost—based immunotherapy of chronic hepatitis B virus infection in a chimpanzee

Preeti Pancholi, Dong‐Hun Lee, Qingyan Liu, Charles Tackney, Patricia Taylor, Marion Perkus, Linda Andrus, Betsy Brotman, Alfred M. Prince – 30 December 2003 – There are about 200 million chronic hepatitis B virus (HBV) carriers at high risk of development of cirrhosis and hepatocellular carcinoma. Termination of the carrier state may avert these risks. We have investigated immunotherapy for chronic HBV infection in a chimpanzee HBV carrier using recombinant DNA‐based immunization followed by a recombinant canarypox booster.

Increased activity in the biliary con A–binding fraction accounts for the difference in crystallization behavior in bile from Chilean gallstone patients compared with Dutch gallstone patients

Juan Francisco Miquel, Joris van der Putten, Fernando Pimentel, Kam S. Mok, Albert K. Groen – 30 December 2003 – Chile has one of the highest prevalences of cholesterol gallstone disease in the world. Recent data indicate that this is partly caused by genetic (Indian) factors. However, the causal factors inducing increased gallstone formation have not been elucidated. The aim of this study was to compare biliary composition and cholesterol crystallization in bile from patients of high and moderate risk areas (Chile and The Netherlands) for gallstone disease.

Halofuginone to prevent and treat thioacetamide‐induced liver fibrosis in rats

Rafael Bruck, Olga Genina, Hussein Aeed, Rosaly Alexiev, Arnon Nagler, Yona Avni, Mark Pines – 30 December 2003 – Hepatic fibrosis is associated with activation of hepatic stellate cells (HSC), the major source of the extracellular matrix (ECM) proteins. The predominant ECM protein synthesized by the HSC is collagen type I. We evaluated the effect of halofuginone—an inhibitor of collagen synthesis—on thioacetamide (TAA)‐induced liver fibrosis in rats.

Bacterial lipopolysaccharide enhances aflatoxin B1 hepatotoxicity in rats by a mechanism that depends on tumor necrosis factor α

C. Charles Barton, Eva X. Barton, Patricia E. Ganey, Steven L. Kunkel, Robert A. Roth – 30 December 2003 – Exposure to a nontoxic dose of bacterial endotoxin (lipopolysaccharide [LPS]) potentiates the hepatotoxicity of aflatoxin B1 (AFB1). Because some of the pathophysiologic effects associated with LPS are mediated through tumor necrosis factor α (TNF‐α), this study was conducted to explore the role of TNF‐α in the AFB1/LPS model.

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