Receptor‐mediated endocytosis of immune complexes in rat liver sinusoidal endothelial cells is mediated by FcγRIIb2

Seyed Ali Mousavi, Marita Sporstøl, Cathrine Fladeby, Rune Kjeken, Nicolas Barois, Trond Berg – 24 August 2007 – Liver sinusoidal endothelial cells (LSECs) display a number of receptors for efficient uptake of potentially injurious molecules. The receptors for the Fc portion of immunoglobulin G (IgG) antibodies (FcγRs) regulate a number of physiological and pathophysiological events. We used reverse transcription polymerase chain reaction (RT‐PCR) and Western blotting to determine the expression of different types of FcγRs in LSECs.

HFE C282Y mutations are associated with advanced hepatic fibrosis in Caucasians with nonalcoholic steatohepatitis

James E. Nelson, Renuka Bhattacharya, Keith D. Lindor, Naga Chalasani, Stuart Raaka, E. Jenny Heathcote, Emil Miskovsky, Eldon Shaffer, Stephen J. Rulyak, Kris V. Kowdley – 24 August 2007 – Previous studies examining the relationship between HFE mutations and severity of nonalcoholic steatohepatitis (NASH) have been limited by small sample size or ascertainment bias. The aim of this study was to examine the relationship between HFE mutations and histological severity in a large North American multicenter cohort with NASH.

Diagnostic accuracy of the aspartate aminotransferase‐to‐platelet ratio index for the prediction of hepatitis C–related fibrosis: A systematic review

Abdel Aziz M. Shaheen, Robert P. Myers – 24 August 2007 – The development of noninvasive markers of liver fibrosis is a clinical and research priority. The aspartate aminotransferase‐to‐platelet ratio index (APRI) is a promising tool with limited expense and widespread availability. Our objective was to systematically review the performance of the APRI in hepatitis C virus (HCV)–infected patients.

Seroprevalence of hepatitis C virus and hepatitis B virus among San Francisco injection drug users, 1998 to 2000

Fan‐Chen Tseng, Thomas R. O'Brien, Mingdong Zhang, Alex H. Kral, Betty A. Ortiz‐Conde, Jennifer Lorvick, Michael P. Busch, Brian R. Edlin – 24 August 2007 – Previous studies suggest that most injection drug users (IDUs) become infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) soon after initiating drug use. The Urban Health Study (UHS) recruited serial cross‐sections of IDUs in the San Francisco Bay area from 1986 to 2005. In the current study, we determined the prevalence of antibody to HCV and HBV (core) among UHS participants during 1998 to 2000.

In vitro production of Mallory bodies and intracellular hyaline bodies: The central role of sequestosome 1 / p62

Conny Stumptner, Andrea Fuchsbichler, Kurt Zatloukal, Helmut Denk – 24 August 2007 – Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are characteristic hepatocellular inclusions. MBs are hallmarks of steatohepatitis, whereas IHBs have first been detected in hepatocellular carcinoma. MBs and IHBs contain ubiquitin and sequestosome 1 / p62 (p62), a stress‐inducible adapter protein with affinity to polyubiquitinated proteins. MBs differ from IHBs by their keratin content and morphology.

Interleukin‐6 inhibits oxidative injury and necrosis after extreme liver resection

Xiaoling Jin, Zongxiu Zhang, Donna Beer‐Stolz, Teresa A. Zimmers, Leonidas G. Koniaris – 24 August 2007 – Extreme hepatectomy or resection of more than 80% of liver mass often leads to liver failure and death and is a major limitation to therapeutic liver resection for patients with liver tumors. We sought to define the mechanisms leading to liver failure and to determine the utility of interleukin‐6 (IL‐6) administration to improve outcomes.

Telaprevir and pegylated interferon–alpha‐2a inhibit wild‐type and resistant genotype 1 hepatitis C virus replication in patients

Tara L. Kieffer, Christoph Sarrazin, Janice S. Miller, Martin W. Welker, Nicole Forestier, Hendrik W. Reesink, Ann D. Kwong, Stefan Zeuzem – 24 August 2007 – Telaprevir (VX‐950) is an orally active, specifically targeted antiviral therapy for hepatitis C virus (HCV) that has been shown to profoundly reduce plasma HCV RNA in genotype 1 patients. Using a highly sensitive sequencing assay that detects minor populations of viral variants (≥5%), mutations were identified that conferred low‐level (V36M/A, T54A, or R155K/T) or high‐level (A156V/T and 36/155) resistance to telaprevir in vitro.

Antiviral activity of telaprevir (VX‐950) and peginterferon alfa‐2a in patients with hepatitis C

Nicole Forestier, Hendrik W. Reesink, Christine J. Weegink, Lindsay McNair, Tara L. Kieffer, Hui‐May Chu, Susan Purdy, Peter L.M. Jansen, Stefan Zeuzem – 24 August 2007 – Telaprevir (VX‐950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa‐2a for 14 days.

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