Vaniprevir with pegylated interferon alpha‐2a and ribavirin in treatment‐naïve patients with chronic hepatitis C: A randomized phase II study

Michael P. Manns, Edward Gane, Maribel Rodriguez‐Torres, Albrecht Stoehr, Chau‐Ting Yeh, Patrick Marcellin, Richard T. Wiedmann, Peggy M. Hwang, Luzelena Caro, Richard J.O. Barnard, Andrew W. Lee, for the MK‐7009 Protocol 007 Study Group – 2 April 2012 – Vaniprevir (MK‐7009) is a macrocyclic hepatitis C virus (HCV) nonstructural protein 3/4A protease inhibitor. The aim of the present phase II study was to examine virologic response rates with vaniprevir in combination with pegylated interferon alpha‐2a (Peg‐IFN‐α‐2a) plus ribavirin (RBV).

Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions

Andreas E. Kremer, Remco van Dijk, Pamela Leckie, Frank G. Schaap, Edith M.M. Kuiper, Thomas Mettang, Katrin S. Reiners, Ulrike Raap, Henk R. van Buuren, Karel J. van Erpecum, Nathan A. Davies, Christian Rust, Andreas Engert, Rajiv Jalan, Ronald P.J. Oude Elferink, Ulrich Beuers – 2 April 2012 – Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus.

Interleukin‐22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice

Xiaoni Kong, Dechun Feng, Hua Wang, Feng Hong, Adeline Bertola, Fu‐Sheng Wang, Bin Gao – 2 April 2012 – Interleukin (IL)‐22 is known to play a key role in promoting antimicrobial immunity, inflammation, and tissue repair at barrier surfaces by binding to the receptors, IL‐10R2 and IL‐22R1. IL‐22R1 is generally thought to be expressed exclusively in epithelial cells. In this study, we identified high levels of IL‐10R2 and IL‐22R1 expression on hepatic stellate cells (HSCs), the predominant cell type involved in liver fibrogenesis in response to liver damage.

Hepatic vein arrival time as assessed by contrast‐enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis

Moon Young Kim, Ki Tae Suk, Soon Koo Baik, Hyoun A. Kim, Young Ju Kim, Seung Hwan Cha, Hwa Ryun Kwak, Mee Yon Cho, Hong Jun Park, Hyo Keun Jeon, So Yeon Park, Bo Ra Kim, Jin Heon Hong, Ki Won Jo, Jae Woo Kim, Hyun Soo Kim, Sang Ok Kwon, Sei Jin Chang, Gwang Ho Baik, Dong Joon Kim – 2 April 2012 – The measurement of the hepatic venous pressure gradient (HVPG) for the estimation of portal hypertension (PH) in cirrhosis has some limitations, including its invasiveness.

Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness

Yonghong Liu, Zhangwei Tong, Ting Li, Qiang Chen, Luting Zhuo, Wengang Li, Ray‐Chang Wu, Chundong Yu – 2 April 2012 – Chronic infection of hepatitis B virus (HBV) is closely associated with the development of human hepatocellular carcinoma (HCC). HBV X protein (HBx) plays a key role in the progression of HCC. We recently found that amplified in breast cancer 1 (AIB1) protein is overexpressed in 68% of human HCC specimens and promotes HCC progression by enhancing cell proliferation and invasiveness.

Liver tumorigenicity promoted by microRNA‐221 in a mouse transgenic model

Elisa Callegari, Bahaeldin K. Elamin, Ferdinando Giannone, Maddalena Milazzo, Giuseppe Altavilla, Francesca Fornari, Luciano Giacomelli, Lucilla D'Abundo, Manuela Ferracin, Cristian Bassi, Barbara Zagatti, Fabio Corrà, Elena Miotto, Laura Lupini, Luigi Bolondi, Laura Gramantieri, Carlo M. Croce, Silvia Sabbioni, Massimo Negrini – 2 April 2012 – MicroRNA‐221 (miR‐221) is one of the most frequently and consistently up‐regulated microRNAs (miRNAs) in human cancer. It has been hypothesized that miR‐221 may act as a tumor promoter.

Ferroportin1 in hepatocytes and macrophages is required for the efficient mobilization of body iron stores in mice

Zhuzhen Zhang, Fan Zhang, Xin Guo, Peng An, Yunlong Tao, Fudi Wang – 2 April 2012 – The liver is a major site of iron storage where sequestered iron can be actively mobilized for utilization when needed elsewhere in the body. Currently, hepatocyte iron efflux mechanisms and their relationships to macrophage iron recycling during the control of whole‐body iron homeostasis are unclear. We hypothesized that the iron exporter, ferroportin1 (Fpn1), is critical for both iron mobilization from hepatocytes and iron recycling from macrophages.

Nanog regulates self‐renewal of cancer stem cells through the insulin‐like growth factor pathway in human hepatocellular carcinoma

Juanjuan Shan, Junjie Shen, Limei Liu, Feng Xia, Chuan Xu, Guangjie Duan, Yanmin Xu, Qinghua Ma, Zhi Yang, Qianzhen Zhang, Leina Ma, Jia Liu, Senlin Xu, Xiaochu Yan, Ping Bie, Youhong Cui, Xiu‐wu Bian, Cheng Qian – 2 April 2012 – Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem‐cell–related genes are preferentially overexpressed in a fraction of cancer cells of poorly differentiated tumors. However, it is not known whether or how these cancer cells contribute to tumor initiation and progression.

IL28B polymorphisms predict interferon‐related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen–negative patients with chronic hepatitis B

Pietro Lampertico, Mauro Viganò, Cristina Cheroni, Floriana Facchetti, Federica Invernizzi, Vincenza Valveri, Roberta Soffredini, Sergio Abrignani, Raffaele De Francesco, Massimo Colombo – 2 April 2012 – Interleukin (IL)28B polymorphisms have been associated with interferon (IFN)‐induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult‐to‐cure hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (CHB) is unknown.

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