Drug‐Induced liver injury with hypersensitivity features has a better outcome: A single‐center experience of 39 children and adolescents

Harshad Devarbhavi, Dheeraj Karanth, Prasanna KS, Adarsh CK, Mallikarjun Patil – 6 July 2011 – Drug‐induced liver injury (DILI) is rare in children and adolescents, and, consequently, data are remarkably limited. We analyzed the causes, clinical and biochemical features, natural history, and outcomes of children with DILI. Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010 (prospective) were studied based on standard criteria for DILI. Thirty‐nine children constituted 8.7% of 450 cases of DILI. There were 22 boys and 17 girls.

The G‐Protein‐coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light‐chain enhancer of activated B cells (NF‐κB) in mice

Yan‐Dong Wang, Wei‐Dong Chen, Donna Yu, Barry M. Forman, Wendong Huang – 6 July 2011 – Gpbar1 (TGR5), a membrane‐bound bile acid receptor, is well known for its roles in regulation of energy homeostasis and glucose metabolism. TGR5 also displays strong attenuation of macrophage reactivity in vitro, but the physiological roles of TGR5 in inflammatory response, and its mechanism, is unknown. Here, we demonstrate that TGR5 is a negative modulator of nuclear factor kappa light‐chain enhancer of activated B cells (NF‐κB)‐mediated inflammation.

Novel feedback inhibition of surface antigen synthesis by mammalian target of rapamycin (mTOR) signal and its implication for hepatitis B virus tumorigenesis and therapy

Chiao‐Fang Teng, Han‐Chieh Wu, Hung‐Wen Tsai, Her‐Shyong Shiah, Wenya Huang, Ih‐Jen Su – 6 July 2011 – Ground glass hepatocytes (GGHs) harboring hepatitis B virus (HBV) pre‐S mutants have been recognized as precursor lesions of hepatocellular carcinoma (HCC). Previously, we observed the activation of mammalian target of rapamycin (mTOR) in GGHs and HCCs, together with a decreased expression of HBV surface antigen (HBsAg) in HCC tissues. It is, therefore, hypothesized that the activation of mTOR during HBV tumorigenesis may potentially down‐regulate HBsAg expression.

Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes

Budhaditya Mazumdar, Arup Banerjee, Keith Meyer, Ranjit Ray – 6 July 2011 – Our previous studies demonstrated that hepatitis C virus (HCV) envelope glycoproteins 1 and 2 (E1 and E2) display distinct reactivity to different cell‐surface molecules. In this study, we characterized the interaction of E1 and E2 with apolipoproteins in facilitating virus entry.

Gankyrin‐mediated dedifferentiation facilitates the tumorigenicity of rat hepatocytes and hepatoma cells

Wen Sun, Jin Ding, Kun Wu, Bei‐Fang Ning, Wen Wen, Han‐Yong Sun, Tao Han, Lei Huang, Li‐Wei Dong, Wen Yang, Xing Deng, Zhong Li, Meng‐Chao Wu, Gen‐Sheng Feng, Wei‐Fen Xie, Hong‐Yang Wang – 6 July 2011 – Gankyrin is a critical oncoprotein overexpressed in human hepatocellular carcinoma (HCC). However, the mechanism underlying gankyrin‐mediated hepatocarcinogenesis remains elusive. Herein, we provide evidence that gankyrin expression was progressively elevated in liver fibrosis, cirrhosis, and HCC.

Fine phenotypic and functional characterization of effector cluster of differentiation 8 positive T cells in human patients with primary biliary cirrhosis

Masanobu Tsuda, Yoko M. Ambrosini, Weici Zhang, Guo‐Xiang Yang, Yugo Ando, Guanghua Rong, Koichi Tsuneyama, Kosuke Sumida, Shinji Shimoda, Christopher L. Bowlus, Patrick S.C. Leung, Xiao‐Song He, Ross L. Coppel, Aftab A. Ansari, Zhe‐Xiong Lian, M. Eric Gershwin – 6 July 2011 – In primary biliary cirrhosis (PBC), patients develop a multilineage response to a highly restricted peptide of the E2 component of pyruvate dehydrogenase (PDC‐E2) involving autoantibody and autoreactive cluster of differentiation (CD)4+ and CD8+ T‐cell responses.

Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice

Alexandre Louvet, Fatima Teixeira‐Clerc, Marie‐Noële Chobert, Vanessa Deveaux, Catherine Pavoine, Andreas Zimmer, Françoise Pecker, Ariane Mallat, Sophie Lotersztajn – 6 July 2011 – Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease. Because cannabinoid CB2 receptors (CB2) display potent anti‐inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis.

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