Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α. HBeAg seroconversion using pegylated IFN-α is 33%, with only 25% of HBeAg-positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops

in 25% of HBeAg-positive and 11% HBeAg-negative Torin 1 order patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted.

Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very SCH772984 in vitro potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infection. With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is an important global disease. It is estimated that more than 400 million people have been chronically infected

with the hepatitis B virus (HBV).1 It is of even more importance to the Asia Pacific region since 75% of those infected with HBV are Asians.1 Up to 40% of these CHB patients will develop the long-term, devastating learn more complications of liver failure (due to liver decompensation from cirrhosis or severe acute exacerbations of CHB2 and hepatocellular carcinoma (HCC).3,4 These complications substantially reduce life expectancy and quality of life, as well as imposing great demands on healthcare resources. Although, the beneficial effects of universal HBV vaccination in reducing the number of CHB patients is already apparent in the younger population,5 the incidence of HCC remains high in most Asian countries.3 Therefore, effective treatment of CHB is still urgently needed.