The World Health Organization estimates that approximately 400 million people are chronically infected with HBV, worldwide, including 1.25 million in the United States. Chronic HBV infection is responsible for 80% of primary liver cancer and liver cancer is currently ranked as the 5th most frequent form of cancer diagnosed worldwide. HBV impacts healthcare systems around the globe and is the 10th leading cause of death worldwide.

Complicating the treatment of chronic HBV infection is the fact that many patients experience only mild non-specific symptoms such as jaundice, fatigue, abdominal pain, loss of appetite, nausea, vomiting and joint pain while others may not experience any symptoms at all. As a consequence, many patients do not even realize they are chronically infected with HBV until the onset of advanced liver disease, when interventional options frequently are more limited or only marginally effective.

From 2000 through 2006, the arsenal of therapeutic agents has expanded from two FDA approved therapies to six approved drugs for HBV. The currently approved HBV therapies are as follows:

HBV, like all viruses, has the ability to mutate and this ability can lead to the emergence of viral resistance in the form of mutant variants that can elude or escape the molecular intervention of antiviral therapeutics. For example, there are known strains of HBV that are resistant to lamivudine. Further, individual patient response rates to HBV therapeutics can vary significantly such that current therapies achieve viral clearance in only a minority of all patients who receive treatment. In some patients, interferon therapy can cause significant side effects that limit a patient's tolerance to the drug, thus preventing many patients from remaining on the therapy long enough to achieve a long term benefit from the treatment.

Unlike Hepatitis B, there is no vaccine available for Hepatitis C virus ("HCV"). As a consequence, the rate of new HCV infections around the world is much higher than for HBV which has an effective vaccine to prevent infection. There are six genotypes of HCV that exist globally, each comprising further subgroups. Additionally the distribution of these genotypes differs geographically. For example, genotypes 1a and 1b are the most prevalent HCV genotypes found within the United States, while genotypes 2 and 3 show a more pronounced presence in other countries.

Chronic HCV infection induces liver inflammation, causing progressive organ damage that can lead to cirrhosis and hepatocellular carcinoma (liver cancer). Chronic HCV infection becomes established in 75%-85% of individuals experiencing an initial infection, and HCV related liver failure is the most common indication cited for liver transplantation in the United States. Similar to chronic HBV infection, chronic HCV infection in its early stages, may cause only mild non-specific symptoms such as fatigue or be completely asymptomatic, leaving many infected individuals unaware that they carry a dangerous chronic infection.

The World Health Organization estimates that 170 million individuals carry chronic HCV infections and that new infections are established at a rate of 3 to 4 million, annually. The U.S. Centers for Disease Control currently estimates chonic HCV infections in the United States at 2.7 million individuals. The total cost of care for HCV related liver disease is estimated to range from $750 million to $1 billion, annually.

The current standard of care for HCV is pegylated interferon in combination with ribavarin. The treatment regimen lasts for 6 to 12 months and can lead to a permanent cure in some patients, depending upon the genotype of HCV infection and other factors not well understood. Response rates to currently approved therapies also vary by genotype, with genotype 2 and 3 patients enjoying a 76% response rate to the current standard of care while patients with genotype 1a and 1b have only a 46% response to the current standard of care.¹ Unfortunately HCV genotype 1 accounts for 60% of global infections and is the dominant strain in the United States, Japan and Western Europe. Complicating genotype 1 resistance to ribavarin and interferon is the fact that both drugs have side effect profiles that can require dose reduction or discontinuance of therapy when patients experience side effects. Further complicating patient outcomes, is the fact that patients who fail an initial treatment regimen rarely respond favorably to a subsequent round of treatment with interferon and ribavarin.

Clinicians who treat HCV patients are hopeful that current and future research programs yield options that improve the response rates for genotype 1 patients, which is currently less than 50%, with ribavarin and interferon. Further new treatment options that have a side effect profile that is more tolerable would improve the quality of HCV patients' lives as they engage in therapy and enable more patients to complete a full and robust course of therapeutic intervention.