Hepatitis B Virus Transgenic Severe Combined Immunodeficient Mouse Model of Acute and Chronic Liver Disease

With the advent of blood tests capable of identifying hepatitis B virus (HBV), and the development of an effective vaccine (1 ), one of the major challenges that remains is what to do with people who are chronic carriers of HBV. This is important because there are an estimated 350 million chronic carriers of HBV worldwide (2 ) who are at high risk for the development of hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (3 ). There are up to a million newly diagnosed cases of HCC each year, making this one of the most common tumor types worldwide. In addition, the risk of carriers developing HCC is in excess of 100, which makes it one of the strongest associations between a cancer and an infectious agent ever reported (4 ). While the survival rate for HCC is < 3% over 5 y, the development of hepatitis is often associated with considerable morbidity, and its progression to cirrhosis is a leading cause of death worldwide. Treatment options for carriers with chronic liver disease are few, with interferon-α (IFN-α), lamivudine, and adefovir dipivoxil the only licensed drugs for clinical use (5 ). Interferon produces a sustained virus response in only about 20% of patients following the end of therapy (5 ,6 ). Lamivudine is highly effective against both virus and liver disease, although a high rate of virus resistance has been reported (7 ,8 ). Adefovir is effective against lamivudine-resistant virus.