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.

Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation

Charbel El Boustany, Gabriel Bidaux, Antoine Enfissi, Philippe Delcourt, Natalia Prevarskaya, Thierry Capiod – 4 February 2008 – Store‐operated calcium entry (SOCE) is the main Ca2+ influx pathway involved in controlling proliferation of the human hepatoma cell lines Huh‐7 and HepG2. However, the molecular nature of the calcium channels involved in this process remains unknown. Huh‐7 and HepG2 cells express transient receptor potential canonical 1 (TRPC1) and TRPC6, as well as STIM1 and Orai1, and these 4 channels are the most likely candidates to account for the SOCE in these cells.

Hepatocyte‐specific inhibitor‐of‐kappaB‐kinase deletion triggers the innate immune response and promotes earlier cell proliferation during liver regeneration

Yann Malato, Leif E. Sander, Christian Liedtke, Malika Al‐Masaoudi, Frank Tacke, Christian Trautwein, Naiara Beraza – 4 February 2008 – Nuclear factor κB (NF‐κB) is one of the main transcription factors involved in liver regeneration after partial hepatectomy (PH). It is activated upon IκB phosphorylation by the IκB kinase (IKK) complex comprising inhibitor of kappaB kinase 1 (IKK1), inhibitor of kappaB kinase 2 (IKK2), and nuclear factor‐B essential modifier (NEMO). We studied the impact of hepatocyte‐specific IKK2 deletion during liver regeneration.

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.

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.

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.

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.

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.

Melittin prevents liver cancer cell metastasis through inhibition of the Rac1‐dependent pathway

Shujing Liu, Mei Yu, Ying He, Lin Xiao, Fang Wang, Changcheng Song, Shuhan Sun, Changquan Ling, Zhiheng Xu – 31 January 2008 – Melittin, a water‐soluble toxic peptide derived from bee venom of Apis mellifera was reported to have inhibitory effects on hepatocellular carcinoma (HCC). However, its role in antimetastasis and the underlying mechanism remains elusive.

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