Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): A histologic marker of advanced NAFLD—Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network

Elizabeth M. Brunt, David E. Kleiner, Laura A. Wilson, Aynur Unalp, Cynthia E. Behling, Joel E. Lavine, Brent A. Neuschwander‐Tetri, NASH Clinical Research Network – 24 February 2009 – Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally‐graded biopsies and temporally‐related clinical parameters from 728 adults and 205 children. From the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) were evaluated.

Switch from Mnt‐Max to Myc‐Max induces p53 and cyclin D1 expression and apoptosis during cholestasis in mouse and human hepatocytes

Heping Yang, Tony W. H. Li, Kwang Suk Ko, Meng Xia, Shelly C. Lu – 24 February 2009 – Toxic bile acids induce hepatocyte apoptosis, for which p53 and cyclin D1 have been implicated as underlying mediators. Both p53 and cyclin D1 are targets of c‐Myc, which is also up‐regulated in cholestasis. Myc and Mnt use Max as a cofactor for DNA binding. Myc‐Max typically activates transcription via E‐box binding. Mnt‐Max also binds the E‐box sequence but serves as a repressor and inhibits the enhancer activity of Myc‐Max.

Hematopoietically expressed homeobox is a target gene of farnesoid X receptor in chenodeoxycholic acid–induced liver hypertrophy

Xiangbin Xing, Elke Burgermeister, Fabian Geisler, Henrik Einwächter, Lian Fan, Michaela Hiber, Sandra Rauser, Axel Walch, Christoph Röcken, Martin Ebeling, Matthew B. Wright, Roland M. Schmid, Matthias P.A. Ebert – 24 February 2009 – Farnesoid X receptor (FXR/Fxr) is a bile acid–regulated nuclear receptor that promotes hepatic bile acid metabolism, detoxification, and liver regeneration. However, the adaptive pathways under conditions of bile acid stress are not fully elucidated.

Induction or expansion of T‐cell responses by a hepatitis B DNA vaccine administered to chronic HBV carriers

Maryline Mancini‐Bourgine, Hélène Fontaine, Daniel Scott‐Algara, Stanislas Pol, Christian Bréchot, Marie‐Louise Michel – 23 February 2009 – Despite the availability of effective hepatitis B vaccines for many years, over 370 million people remain persistently infected with hepatitis B virus (HBV). Viral persistence is thought to be related to poor HBV‐specific T‐cell responses. A phase I clinical trial was performed in chronic HBV carriers to investigate whether HBV DNA vaccination could restore T‐cell responsiveness.

S‐adenosylhomocysteine sensitizes to TNF‐α hepatotoxicity in mice and liver cells: A possible etiological factor in alcoholic liver disease

Zhenyuan Song, Zhanxiang Zhou, Silvia Uriarte, Lipeng Wang, Y. James Kang, Theresa Chen, Shirish Barve, Craig J. McClain – 23 February 2009 – In alcoholic liver disease, tumor necrosis factor‐α (TNFα) is a critical effector molecule, and abnormal methionine metabolism is a fundamental acquired metabolic abnormality. Although hepatocytes are resistant to TNFα‐induced killing under normal circumstances, previous studies have shown that primary hepatocytes from rats chronically fed alcohol have increased TNFα cytotoxicity.

Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death

Douglas M. Heuman, Souheil G. Abou‐assi, Adil Habib, Leslie M. Williams, R. Todd Stravitz, Arun J. Sanyal, Robert A. Fisher, Anastasios A. Mihas – 23 February 2009 – Despite the adoption of “sickest first” liver transplantation, pretransplant death remains common, and many early deaths occur despite initially low Model for End‐stage Liver Disease (MELD) scores. From 1997–2003, we studied 507 cirrhotic United States veterans referred for consideration of liver transplantation to identify additional predictors of early mortality.

Peptide antibiotic human beta‐defensin‐1 and ‐2 contribute to antimicrobial defense of the intrahepatic biliary tree

Kenichi Harada, Kazuo Ohba, Satoru Ozaki, Kumiko Isse, Toshiya Hirayama, Akihiro Wada, Yasuni Nakanuma – 23 February 2009 – Human beta‐defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces. This study was undertaken to investigate the expression of hBD‐1 and hBD‐2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells). In addition, hBD‐1 and hBD‐2 were assayed in specimens of bile.

Interleukin 6 alleviates hepatic steatosis and ischemia/reperfusion injury in mice with fatty liver disease

Feng Hong, Svetlana Radaeva, Hong‐na Pan, Zhigang Tian, Richard Veech, Bin Gao – 23 February 2009 – Fatty liver, formerly associated predominantly with excessive alcohol intake, is now also recognized as a complication of obesity and an important precursor state to more severe forms of liver pathology including ischemia/reperfusion injury. No standard protocol for treating fatty liver exists at this time.

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