Jeremy Cobbold, Adrian Lim, Marzena Wylezinska, Cliona Cunningham, Mary Crossey, Howard Thomas, Nayna Patel, Jane Cox, Simon Taylor‐Robinson – 25 May 2006

Norman M. Kneteman, Amy J. Weiner, John O'Connell, Marc Collett, Tiejun Gao, Lea Aukerman, Rosemary Kovelsky, Zhi‐Jie Ni, Ahmad Hashash, Janine Kline, Belinda Hsi, Daniel Schiller, Donna Douglas, D Lorne J Tyrrell, David F. Mercer – 25 May 2006 – Compounds with in vitro anti‐hepatitis C virus (HCV) activity are often advanced directly into clinical trials with limited or no in vivo efficacy data. This limits prediction of clinical efficacy of compounds in the HCV drug pipeline, and may expose human subjects to unnecessary treatment effects.

Clifford S. Guy, Jinguo Wang, Tomasz I. Michalak – 25 May 2006 – The liver plays an increasingly recognized role in the host's immune responses. The direct contribution of hepatocytes as effector cells to local immunity, pathogen containment, and liver disease is not determined. This in vitro study examined whether hepatocytes can eliminate other cells via a CD95 ligand (CD95L or FasL)/CD95 (Fas)–mediated mechanism and whether this cytotoxic activity can be modulated by cytokines such as interferon gamma (IFN‐γ) or tumor necrosis factor alpha (TNF‐α).

Richard K. Sterling, Eduardo Lissen, Nathan Clumeck, Ricard Sola, Mendes Cassia Correa, Julio Montaner, Mark S. Sulkowski, Francesca J. Torriani, Doug T. Dieterich, David L. Thomas, Diethelm Messinger, Mark Nelson – 25 May 2006 – Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection.

Angelo Sangiovanni, Gian Maria Prati, Pierangelo Fasani, Guido Ronchi, Raffaella Romeo, Matteo Manini, Ersilio Del Ninno, Alberto Morabito, Massimo Colombo – 25 May 2006 – Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years.

Bofeng Li, Rui Sun, Haiming Wei, Bin Gao, Zhigang Tian – 25 May 2006 – Administration of concanavalin A (Con A) induces a rapid and severe liver injury in mice. Natural killer T (NKT) cells are recognized to be the key effector cells, and a variety of cytokines [e.g., interleukin 4 (IL‐4), IL‐5, interferon gamma (IFN‐γ), and tumor necrosis factor alpha (TNF‐α)] have been shown to play vital roles in Con A–induced liver injury, whereas the role of IL‐15, a critical cytokine in the development and homeostasis of NKT cells, remains obscure.

Masaaki Shiina, Barbara Rehermann – 25 May 2006 – Three percent of the world's population is chronically infected with the hepatitis C virus (HCV) and at risk of developing liver cancer. Effective cellular immune responses are deemed essential for spontaneous resolution of acute hepatitis C and long‐term protection. Here we describe a new T‐cell HCV genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by challenge with heterologous virus.

Eishiro Mizukoshi, Yasunari Nakamoto, Yohei Marukawa, Kuniaki Arai, Tatsuya Yamashita, Hirokazu Tsuji, Kiyotaka Kuzushima, Masafumi Takiguchi, Shuichi Kaneko – 25 May 2006 – Human telomerase reverse transcriptase, hTERT, has been identified as the catalytic enzyme required for telomere elongation. hTERT is expressed in most tumor cells but seldom expressed in most human adult cells. It has been reported that 80% to 90% of hepatocellular carcinomas (HCCs) express hTERT, making the enzyme a potential target in immunotherapy for HCC.

David N. Frick – 25 May 2006 – Helicases are a ubiquitous class of enzymes involved in nearly all aspects of DNA and RNA metabolism. Despite recent progress in understanding their mechanism of action, limited resolution has left inaccessible the detailed mechanisms by which these enzymes couple the rearrangement of nucleic acid structures to the binding and hydrolysis of ATP. Observing individual mechanistic cycles of these motor proteins is central to understanding their cellular functions.

Marianne Bonvin, François Achermann, Isabell Greeve, Deborah Stroka, Adrian Keogh, Daniel Inderbitzin, Daniel Candinas, Peter Sommer, Simon Wain‐Hobson, Jean‐Pierre Vartanian, Jobst Greeve – 25 May 2006 – Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication.