Therapy of Hepatitis B Virus Infections - Potential and Limitations

New impulses for HBV therapy came from the appearance and explosive spread of HIV in industrialized countries during the early 1980s. Now, the development for an effective antiviral therapy has received highest priority. The USA spent 3.1 billion US dollar in the time up to 2010 for HIV research, and compared to other viral infections, effective HIV drugs came to the market relatively fast. HBV research, the ‘poor cousin’ of HIV research, received only USD 53 million in the same time period [4] . Due to the reverse transcription present in the life cycles of both HBV and HIV (see articles from Glebe and König [this issue, pp. 134–140] and Gürtler [this issue, pp. 212–217]), it could be presumed that inhibitors of the HIV reverse transcriptase would also be active against HBV. Early in the 1990s it was recognized that the reverse transcriptase inhibitor lamivudine was effective in vitro against HBV [5] , but the first success in patients was observed only as a kind of positive side effect in HIV-coinfected patients [6] . The pharmaceutical industry finally began to intensify their efforts to test their antiviral candidate substances against HBV, which, for example, led to the development of the licensed drugs adefovir, telbivudine, and entecavir. Currently, however, the most potent HBV drug was again an off-spin from HIV therapy. Although van Bömmel et al. [7] and others noted already in 2002 that the HIV drug tenofovir was very effective against HBV in HIV-coinfected patients, industry preferred to introduce in 2003 the closely related, but much less effective, adefovir for therapy of lamivudine-resistant HBV strains. Specific therapy of viral infections has been and still is an underdeveloped field of medicine. While most bacterial infections can be treated with a relatively small set of antibiotics, for most viral infections no drugs are available. There are a few important exceptions, hepatitis B virus (HBV) being one of them. The basis for therapeutic studies on chronic hepatitis B was created by the discovery of the HBV particle by D.S. Dane in 1970 and the HBV DNA polymerase within that particle by W.S. Robinson in 1973 [1] . In a landmark study from T.C. Merigan and W.S. Robinson, chronic hepatitis B was the first infection to be treated with human leukocyte interferon [2] and has remained the only viral infection where interferon has a generally accepted role as pointed out by Brunetto and Bonino in this special issue [pp. 163–170] of Intervirology . Merigan and Robinson soon realized that interferon alone was not the solution because only a minority of patients could be cured. They started to combine interferon with the then available nucleoside analogues as additional drugs against HBV, but the toxicity of these early compounds was too high [3] . Further progress was disappointingly slow, partly because the efforts of the medical community and the pharmaceutical industry were small. One reason for this neglect may have been the amazing efficacy of the hepatitis B vaccine which raised the hope that HBV and the disease hepatitis B may disappear by continuous prevention without additional efforts to treat those who were already infected. This attitude, however, is cynical in view of the roughly 600,000 deaths per year due to chronic HBV infection. Published online: July 15, 2014