A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa‐2a in hepatitis C virus genotypes 2 and 3

Peter Ferenci, Harald Brunner, Hermann Laferl, Thomas‐Matthias Scherzer, Andreas Maieron, Michael Strasser, Gabriele Fischer, Harald Hofer, Martin Bischof, Rudolf Stauber, Michael Gschwantler, Petra Steindl‐Munda, Katharina Staufer, Karin Löschenberger – 4 February 2008 – We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day (group A) or 400 mg/day (group B) plus peginterferon alfa‐2a 180 μg/week in treatment‐naive patients infected with hepatitis C virus (HCV) genotype 2 or 3.

The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells

Samuel Martín‐Vílchez, Paloma Sanz‐Cameno, Yolanda Rodríguez‐Muñoz, Pedro L. Majano, Francisca Molina‐Jiménez, Manuel López‐Cabrera, Ricardo Moreno‐Otero, Enrique Lara‐Pezzi – 4 February 2008 – Chronic hepatitis B virus (HBV) infection is a major cause of liver fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma. Although the involvement of the X protein of HBV (HBx) in viral replication and tumor development has been extensively studied, little is known about its possible role in the development of fibrosis.

MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations

Yannick Ladeiro, Gabrielle Couchy, Charles Balabaud, Paulette Bioulac‐Sage, Laura Pelletier, Sandra Rebouissou, Jessica Zucman‐Rossi – 1 February 2008 – Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features.

Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B

Maureen M. Jonas, Deirdre Kelly, Henry Pollack, Jacek Mizerski, Jeff Sorbel, David Frederick, Elsa Mondou, Franck Rousseau, Etienne Sokal – 1 February 2008 – This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment‐naive and treatment‐experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment.

Randomized comparison of 12 or 24 weeks of peginterferon α‐2a and ribavirin in chronic hepatitis C virus genotype 2/3 infection

Martin Lagging, Nina Langeland, Court Pedersen, Martti Färkkilä, Mads Rauning Buhl, Kristine Mørch, Amar P. Dhillon, Åsa Alsiö, Kristoffer Hellstrand, Johan Westin, Gunnar Norkrans – 1 February 2008 – Previous trials investigating the efficacy of treatment durations shorter than the standard of 24 weeks for chronic hepatitis C virus (HCV) genotype 2/3 infections have yielded discordant results. The aims of this investigator‐initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short‐term therapy.

Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus

Bart J. Veldt, Wendong Chen, E. Jenny Heathcote, Heiner Wedemeyer, Juerg Reichen, W. Peter Hofmann, Robert J. de Knegt, Stefan Zeuzem, Michael P. Manns, Bettina E. Hansen, Solko W. Schalm, Harry L. A. Janssen – 1 February 2008 – Recent studies suggest that diabetes mellitus increases the risk of developing hepatocellular carcinoma (HCC). The aim of this study is to quantify the risk of HCC among patients with both diabetes mellitus and hepatitis C in a large cohort of patients with chronic hepatitis C and advanced fibrosis. We included 541 patients of whom 85 (16%) had diabetes mellitus.

Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor

Hung‐Yun Lin, I‐Chen Yu, Ruey‐Shen Wang, Yei‐Tsung Chen, Ning‐Chun Liu, Saleh Altuwaijri, Cheng‐Lung Hsu, Wen‐Lung Ma, Jenny Jokinen, Janet D. Sparks, Shuyuan Yeh, Chawnshang Chang – 1 February 2008 – Early studies demonstrated that whole‐body androgen receptor (AR)–knockout mice with hypogonadism exhibit insulin resistance. However, details about the mechanisms underlying how androgen/AR signaling regulates insulin sensitivity in individual organs remain unclear.

A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients

Guilherme M. Campos, Kiran Bambha, Eric Vittinghoff, Charlotte Rabl, Andrew M. Posselt, Ruxandra Ciovica, Umesh Tiwari, Linda Ferrel, Mark Pabst, Nathan M. Bass, Raphael B. Merriman – 31 January 2008 – Nonalcoholic steatohepatitis (NASH) is common in morbidly obese persons. Liver biopsy is diagnostic but technically challenging in such individuals. This study was undertaken to develop a clinically useful scoring system to predict the probability of NASH in morbidly obese persons, thus assisting in the decision to perform liver biopsy.

Prevention of free fatty acid–induced hepatic lipotoxicity by 18β‐glycyrrhetinic acid through lysosomal and mitochondrial pathways

Xudong Wu, Luyong Zhang, Emily Gurley, Elaine Studer, Jing Shang, Tao Wang, Cuifen Wang, Ming Yan, Zhenzhou Jiang, Phillip B. Hylemon, Arun J. Sanyal, William M. Pandak, Huiping Zhou – 31 January 2008 – Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and affects millions of people worldwide. Despite the increasing prevalence of NAFLD, the exact molecular/cellular mechanisms remain obscure and effective therapeutic strategies are still limited. It is well‐accepted that free fatty acid (FFA)‐induced lipotoxicity plays a pivotal role in the pathogenesis of NAFLD.

Virological and immunological determinants of intrahepatic virus‐specific CD8+ T‐cell failure in chronic hepatitis C virus infection

Christoph Neumann‐Haefelin, Jörg Timm, Hans Christian Spangenberg, Natalie Wischniowski, Natalja Nazarova, Nadine Kersting, Michael Roggendorf, Todd M. Allen, Hubert E. Blum, Robert Thimme – 31 January 2008 – Virus‐specific CD8+ T‐cells play an important role in the outcome of acute hepatitis C virus (HCV) infection. In the chronic phase, however, HCV can persist despite the presence of virus‐specific T‐cell responses.

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