CD56+ T cells inhibit hepatitis C virus replication in human hepatocytes

Li Ye, Xu Wang, Shihong Wang, Yanjian Wang, Li Song, Wei Hou, Lin Zhou, He Li, Wenzhe Ho – 24 February 2009 – CD56+ T cells are abundant in liver and play an important role in defense against viral infections. However, the role of CD56+ T cells in control of hepatitis C virus (HCV) infection remains to be determined. We investigated the noncytolytic anti‐HCV activity of primary CD56+ T cells in human hepatocytes.

Deficiency of nicotinamide adenine dinucleotide phosphate, reduced form oxidase enhances hepatocellular injury but attenuates fibrosis after chronic carbon tetrachloride administration

Ghazaleh Aram, James J. Potter, Xiaopu Liu, Lan Wang, Michael S. Torbenson, Esteban Mezey – 24 February 2009 – Reactive oxygen species (ROS) activate hepatic stellate cells and enhance fibrogenesis. This study determined the role of nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase deficiency in the development of hepatocellular necrosis, inflammation, and apoptosis in relation to fibrosis produced by chronic carbon tetrachloride (CCl4) administration.

Unique phenotype of hepatocellular cancers with exon‐3 mutations in beta‐catenin gene

Benjamin Cieply, Gang Zeng, Tracy Proverbs‐Singh, David A. Geller, Satdarshan P. S. Monga – 24 February 2009 – Wnt/β‐catenin signaling plays an important role in liver development and regeneration. Its aberrant activation, however, is observed in a subset of primary hepatocellular cancers (HCCs). In the current study, we compare and contrast the tumor characteristics of HCC in the presence or absence of mutations in the β‐catenin gene (CTNNB1).

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.

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