From Germany to Hawaii, everyone's talking about hepatitis B. Scientists from the Hepatitis B Foundation (HBF) presented at the International Meeting on the Molecular Biology of Hepatitis B Viruses (HBV 2005) and HepDART 2005: Frontiers in Drug Development for Viral Hepatitis. The advances and challenges in hepatitis B research are being discussed by the best and brightest in the field. The HBF is proud to help sponsor both conferences, which help keep hepatitis B in the global spotlight.

HBV 2005 was held in historic Heidelberg, Germany, in September, and cochaired by Dr. Timothy Block, HBF president and professor of Drexel University College of Medicine (Phila., PA), and Dr. Stephan Urban, professor of University of Heidelberg (Germany).

This year marks the 20th anniversary of HBV 2005, which was started by Drs. Jesse Summers and Harold Varmus in 1985, and it remains the definitive international meeting that covers all aspects of the biology of the hepatitis B and D viruses.

In December, more than 350 people made the bi-annual pilgrimage to Hawaii, making this year's HepDART 2005 the largest meeting ever. The increased number of participants probably reflects a combination of the maturation of hepatitis B (HBV) therapeutics as well as a rapidly increasing interest in hepatitis C (HCV). HepDART is organized by Drs. Raymond Schinazi, Charles Rice, Jean-Pierre Sommadossi, and Charles Murphy.

Although HCV continues to consume the most attention at HepDART, given the growing number of HBV therapeutics, interest in hepatitis B remains high. In addition, the continued commitment of coorganizer Dr. Raymond Schinazi, assures that HBV gets a fair share of attention.

At HepDART 2005, held December 11-15 in Kona, Hawaii, the HBF led a session devoted to hepatocellular carcinoma (HCC) or primary liver cancer. In his introduction, Dr. Timothy Block, HBF president, announced that the treatment of HCC has been declared a new HBF priority and that there is an increasing urgency for HCC therapeutics, which is in an early stage of development. Dr. Thomas London, Fox Chase Cancer Center and HBF board member, served as moderator of the session. He emphasized that HCC is the only cancer that is increasing in the U.S., and that worldwide 600,000 people die each year from HCC (80% of all cases are caused by HBV). Dr. Eddie Cheung, U. of California-Davis, reviewed current treatment options and Dr. Robert Gish, CA Pacific Medical Center, envisioned future prospects of HCC therapy.

Current options for HCC management are fairly limited since there are no FDA-approved medications (see "Therapies for Liver Cancer" in B Informed, spring 2005). In the next 5 to 10 years, customized treatments that are patient-specific are anticipated. Everyone agreed that early detection of HCC is vital, and new imaging technologies and new blood tests should soon be available.

In addition to a review of the impressive performances of newer approved HBV oral antivirals (Hepsera, Baraclude), it seems likely that new antivirals such as telbivudine, and perhaps clevudine, will also be available within the next two years. There is also something of a revival (or rediscovery) of interferon with the approval of pegylated interferon.

Gene silencing of HBV (Dr.Morrissey, Sirna Therapeutics), toll receptor mediated therapies (Dr. Averett, Anadys, Inc), and even treatment with apoptosis inhibitors (Dr. Shapiro, Integrated Quality Resources) were examples of some of the newer HBV therapeutic approaches. A discussion by Dr. Locarnini (Melbourne, Australia) about how HBV disease is really several different syndromes was particularly provocative.

Framing the Knowledge of Therapeutics for Viral Hepatitis, edited by Raymond Schinazi and Eugene Schiff, was released at HepDART 2005 and comprises 25 chapters detailing the advances and challenges in the field. The book is dedicated to Baruch Blumberg, who won the Nobel Prize for his discovery of the hepatitis B virus. IHL Press has generously offered to donate 5% of the book proceeds to the Hepatitis B Foundation. So visit www.ihlpress.com to order your copy today!

HBV 2005 was held Sept. 18-21, 2005, in historic Heidelberg, and co-chaired by Drs. Timothy Block and Stephan Urban. The antiviral session featured several presentations on the stability and management of cccDNA, which is the main reservoir of HBV in the infected liver. Removal of cccDNA is important for the ultimate control of the virus. Alternative approaches to the control of HBV were also intensely discussed such as methods to inhibit virus infection using short pieces of a specific HBV protein, the development of short hairpin RNA molecules as antivirals against HBV, and the use of the anticancer agent Velcade(r) against HBV.

Additional highlights included talks by Dr. Anand Mehta, HBF Bruce Witte Scholar, who presented data on behalf of his colleagues at Drexel, Drs. Tianlun Zhou and Haitao Guo, about a system to screen for inhibitors of cccDNA. Dr. Karsten Wursthorn provided evidence that the decline of cccDNA in people treated with pegylated interferon and adefovir was the result of a loss in the infected cells, as opposed to a direct effect on cccDNA. Dr.William Mason presented a hypothetical look at the rate of infected cell turnover and the development of drug-resistant mutations. Efforts are underway to find a direct inhibitor of the HBV cccDNA; however, it remains to be seen if such an inhibitor can be found.

Dr. Stephan Urban reported on a method utilizing small, modified pieces of the HBV L protein, peptides, which could inhibit HBV infection both in cell cultures and in an animal model. Even at low doses, these compounds could prevent the establishment of the initial infection. Thus, these compounds could have clinical benefit in transplantation settings and in preventing horizontal transfer of HBV from mother to child.

BInformed, Winter 2006.