Pharmacogenetics of drug‐induced liver injury

Stefan Russmann, Alexander Jetter, Gerd A. Kullak‐Ublick – 23 July 2010 – Recent progress in research on drug‐induced liver injury (DILI) has been determined by key developments in two areas. First, new technologies allow the identification of genetic risk factors with improved sensitivity, specificity, and efficiency. Second, new mechanistic concepts of DILI emphasize the importance of unspecific “downstream” events following drug‐specific initial “upstream” hepatocyte injury and of complex interactions between environmental and genetic risk factors.

The specificity of fatigue in primary biliary cirrhosis: Evaluation of a large clinic practice

Nadya Al‐Harthy, Teru Kumagi, Catalina Coltescu, Gideon M. Hirschfield – 23 July 2010 – Quality of life is an important concern for patients with chronic liver disease. We sought to describe the frequency, severity, and associations of fatigue, in patients with primary biliary cirrhosis (PBC). We performed association testing between PBC‐40 multidomain disease‐specific quality of life responses and clinical findings. Three hundred twenty‐seven patients from a single clinic with PBC (94% female, 92% AMA‐positive) were evaluated.

Involvement of PA28γ in the propagation of hepatitis C virus

Kohji Moriishi, Ikuo Shoji, Yoshio Mori, Ryosuke Suzuki, Tetsuro Suzuki, Chikako Kataoka, Yoshiharu Matsuura – 23 July 2010 – We have reported previously that the proteasome activator PA28γ participates not only in degradation of hepatitis C virus (HCV) core protein in the nucleus but also in the pathogenesis in transgenic mice expressing HCV core protein. However, the biological significance of PA28γ in the propagation of HCV has not been clarified. PA28γ is an activator of proteasome responsible for ubiquitin‐independent degradation of substrates in the nucleus.

Association between serum uric acid level and chronic liver disease in the United States

Anita Afzali, Noel S. Weiss, Edward J. Boyko, George N. Ioannou – 23 July 2010 – Elevated serum uric acid (UA) levels strongly reflect and may even cause oxidative stress, insulin resistance, and metabolic syndrome, which are risk factors for the progression of liver disease. We sought to determine whether serum UA levels are associated with the development of cirrhosis or the presence of elevated serum liver enzymes.

Human immunodeficiency virus (HIV)‐1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein‐1 expression: Implications for the pathogenesis of HIV/hepatitis C virus–induced liver fibrosis

Ana C. Tuyama, Feng Hong, Yedidya Saiman, Chuansheng Wang, Derya Ozkok, Arevik Mosoian, Ping Chen, Benjamin K. Chen, Mary E. Klotman, Meena B. Bansal – 23 July 2010 – Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) develop more rapid fibrosis than those infected with HCV only. In HIV/HCV‐coinfected patients, fibrosis progression correlates with HIV RNA levels, suggesting a direct role of HIV in liver fibrogenesis.

Thiazolidinediones inhibit hepatocarcinogenesis in hepatitis B virus–transgenic mice by peroxisome proliferator‐activated receptor γ–independent regulation of nucleophosmin

Andrea Galli, Elisabetta Ceni, Tommaso Mello, Simone Polvani, Mirko Tarocchi, Francesca Buccoliero, Francesca Lisi, Laura Cioni, Barbara Ottanelli, Valeria Foresta, Guido Mastrobuoni, Gloriano Moneti, Giuseppe Pieraccini, Calogero Surrenti, Stefano Milani – 23 July 2010 – Antidiabetic thiazolidinediones (TZD) have in vitro antiproliferative effect in epithelial cancers, including hepatocellular carcinoma (HCC). The effective anticancer properties and the underlying molecular mechanisms of these drugs in vivo remain unclear.

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