The causes of primary biliary cirrhosis: Convenient and inconvenient truths

M. Eric Gershwin, Ian R. Mackay – 26 January 2008 – The most difficult issue in autoimmunity remains etiology. Although data exist on effector mechanisms in many autoimmune diseases, the underlying cause or causes are still generically ascribed to genetics and environmental influences. Primary biliary cirrhosis (PBC) is considered a model autoimmune disease because of its signature antimitochondrial autoantibody (AMA), the homogeneity of clinical characteristics, and the specificity of biliary epithelial cell (BEC) pathology.

Behavior therapy for nonalcoholic fatty liver disease: The need for a multidisciplinary approach

Stefano Bellentani, Riccardo Dalle Grave, Alessandro Suppini, Giulio Marchesini, Fatty Liver Italian Network (FLIN) – 26 January 2008 – Nonalcoholic fatty liver disease (NAFLD) is systematically associated with insulin resistance and the metabolic syndrome, where behavior therapy remains the primary treatment, simultaneously addressing all the clinical and biochemical defects.

Systemic transmigration of allosensitizing donor dendritic cells to host secondary lymphoid organs after rat liver transplantation

Hisashi Ueta, Changde Shi, Nobutomo Miyanari, Xue‐Dong Xu, Shu Zhou, Masaki Yamashita, Taichi Ezaki, Kenjiro Matsuno – 25 January 2008 – Donor dendritic cell (DC) migration and allosensitization in host secondary lymphoid organs after liver transplantation are ill defined. We used rat models to investigate graft‐derived cells and intrahost allosensitization.

Mesenchymal stem cell–derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo

Daan van Poll, Biju Parekkadan, Cheul H. Cho, François Berthiaume, Yaakov Nahmias, Arno W. Tilles, Martin L. Yarmush – 24 January 2008 – Orthotopic liver transplantation is the only proven effective treatment for fulminant hepatic failure (FHF), but its use is limited because of organ donor shortage, associated high costs, and the requirement for lifelong immunosuppression. FHF is usually accompanied by massive hepatocellular death with compensatory liver regeneration that fails to meet the cellular losses.

Caspase activation is associated with spontaneous recovery from acute liver failure

Xandra Volkmann, Matthias Anstaett, Johannes Hadem, Penelope Stiefel, Matthias J. Bahr, Frank Lehner, Michael P. Manns, Klaus Schulze‐Osthoff, Heike Bantel – 24 January 2008 – Acute liver failure (ALF) has various causes and is characterized by rapid hepatocyte dysfunction with development of encephalopathy in the absence of preexisting liver disease. Whereas most patients require liver transplantation to prevent the high mortality, some patients recover spontaneously and show complete liver regeneration.

The hepatic stem cell niche: Identification by label‐retaining cell assay

Reiichiro Kuwahara, Alexander V. Kofman, Charles S. Landis, E. Scott Swenson, Els Barendswaard, Neil D. Theise – 21 January 2008 – Label retention assays remain the state‐of‐the‐art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow.

Noninvasive assessment of hepatic lipid composition: Advancing understanding and management of fatty liver disorders

Nathan A. Johnson, David W. Walton, Toos Sachinwalla, Campbell H. Thompson, Kate Smith, Patricia A. Ruell, Stephen R. Stannard, Jacob George – 21 January 2008 – Nonalcoholic fatty liver is frequently observed in obese individuals, yet the factors that predict its development and progression to liver disease are poorly understood. We proposed that proton magnetic resonance spectroscopy (1H‐MRS) might allow noninvasive assessment of hepatic lipid composition.

Temporal‐spatial activation of apoptosis and epithelial injury in murine experimental biliary atresia

Nissa Erickson, Sujit Kumar Mohanty, Pranavkumar Shivakumar, Gregg Sabla, Ranajit Chakraborty, Jorge A. Bezerra – 21 January 2008 – Biliary atresia is a fibro‐inflammatory cholangiopathy that obstructs the extrahepatic bile ducts in young infants. Although the pathogenesis of the disease is undefined, studies in livers from affected children and neonatal mice with experimental biliary atresia have shown increased expression of proapoptosis molecules. Therefore, we hypothesized that apoptosis is a significant mechanism of injury to duct epithelium.

β‐Catenin deletion in hepatoblasts disrupts hepatic morphogenesis and survival during mouse development

Xinping Tan, Youzhong Yuan, Gang Zeng, Udayan Apte, Michael D. Thompson, Benjamin Cieply, Donna B. Stolz, George K. Michalopoulos, Klaus H. Kaestner, Satdarshan P.S. Monga – 21 January 2008 – β‐Catenin, the central component of the canonical Wnt pathway, plays important roles in the processes of liver regeneration, growth, and cancer. Previously, we identified temporal expression of β‐catenin during liver development.

Cytochrome P450 2E1 contributes to ethanol‐induced fatty liver in mice

Yongke Lu, Jian Zhuge, Xiaodong Wang, Jingxiang Bai, Arthur I. Cederbaum – 21 January 2008 – Cytochrome P450 2E1 (CYP2E1) is suggested to play a role in alcoholic liver disease, which includes alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. In this study, we investigated whether CYP2E1 plays a role in experimental alcoholic fatty liver in an oral ethanol‐feeding model. After 4 weeks of ethanol feeding, macrovesicular fat accumulation and accumulation of triglyceride in liver were observed in wild‐type mice but not in CYP2E1‐knockout mice.

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