Chae and Hann later, is currently on tenofovir (TDF) after suboptimal response to ADV. Now at the age of 64, he has remained a very suc- cessful businessman with normal liver function, undetectable serum HBV DNA and without recurrent or new HCC. A 49 year-old Asian American man received IFN therapy for 4 months (3/94–7/94) but without HBeAg conversion. He received no therapy despite having ALT elevation until 5/96 when LVD (as Epivir) became available. LVD therapy was discontinued in 11/99 after HBeAg seroconversion and he relapsed in 9/02. Retreatment with LVD resulted in undetectable HBV DNA and LVD therapy was discontinued in 11/04. He is now 61 years old with normal liver function with undetectable HBV DNA and remains well. The cases described above clearly illustrate how antiviral agents could successfully halt the progression of liver disease or development of new HCC in patients with CHB. Introduction There are nearly 350 million HBV carriers worldwide (Lee 1997). These carriers are at risk for development of cirrho- sis, HCC and death. Recently, Chen et al (2006) in Taiwan reported the results of their 12 year follow-up study, the REVEAL-HBV study (Risk Evaluation of Viral load Eleva- tion and Associated Liver disease/cancer). They found that elevated serum HBV DNA level 10,000 copies/mL was the most important risk factor for HCC independent of HBeAg, serum alanine aminotransferase (ALT) and liver cirrhosis. In this elegant study the authors followed 3653 HBsAg(+) carriers (aged 30–65 years) for a mean follow-up of 11.4 years and during this period 164 persons developed HCC. The incidence of HCC increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108/100,000 person-years for an HBV DNA level of 300 copies/mL to 1152/100,000 person-years for an HBV DNA level of 1,000,000 copies/mL. Also, Liaw et al (2004), in a trial of 651 CHB patients with cirrhosis or advanced ﬁbrosis from several countries in Asia, randomized 2/3 of patients to receive LVD and 1/3 of patients to receive placebo. In less than 3 years on study the authors observed that those who received LVD not only showed delayed disease progression but also had reduced incidence of HCC compared to those on placebo. These two landmark studies reafﬁrm the need for an active approach for patients with CHB with an antiviral therapy. The aims of treatment of CHB are to achieve sustained suppression of HBV replication and remission of liver dis- ease. The end points include normalization of serum ALT level, undetectable serum HBV DNA by an ampliﬁed assay, 606 loss of HBeAg, with or without detection of anti-HBe, and improvement of liver histology (Lok and McMahon 2004). The ultimate long-term goal of therapy is to prevent hepatic decompensation, to reduce or prevent progression to cirrhosis and/or HCC, and to prolong survival (Liaw et al 2005). In 1992, interferon alpha (IFN-α) was ﬁrst introduced for the treatment of CHB. As of November 2006, there are six FDA approved drugs available for the treatment of CHB in the United States, including two formulations of interferon and four oral nucleos(t)ide agents. With multiple therapeutic agents available, there is a great need for physicians to have sufﬁcient knowledge to provide the best choice of treatment for their patients. While these drugs are all highly effective, there are differences in drug safety, cost, drug resistance and risks of disease ﬂare from premature discontinuation of therapy or from poor compli- ance on the part of patients. In addition, the disease may recur even after treatment and therefore, close follow-up after the completion of therapy is important. Furthermore, close monitoring for early detection of HCC is essential during and after the treatment. As strong advocates for an active and earliest possible intervention for CHB with antiviral agents, the efﬁcacy, the advantages and disadvantages of currently available therapeutic agents are being examined. Interferon-α2b Interferon-α2b (IFN-α2b) became available in 1992 and remained the only FDA approved agent for the treatment of CHB until 1998. IFN-α2b has direct effects on the immune system, including enhanced expression of HLA class I mol- ecules and stimulation of CD8+ cytotoxic T-cell activity. The duration of treatment ranges between 4 to 6 months by subcutaneous injection of 5 million units daily or 10 million units three times weekly. This regimen results in HBeAg loss in 30%–40% of patients and clearance of HBsAg in 10% of patients. Studies from North America and Europe have shown HBeAg loss in 30%–35% of patients who are treated with 4 to 6 months of interferon-α2b (Perrillo et al 1990). In HBeAg(–) CHB, the response has been deﬁned as undetectable serum HBV DNA by unampliﬁed assays and normalization of ALT level. Results of four randomized trials involving a total of 86 IFN-α2b treated patients and 84 controls showed that the end-of-treatment response ranged from 38 to 90% in treated patients compared with only 0% to 37% of controls. Longer duration of treatment up to 24 months may improve the rate of sustained response (Lok and McMahon 2001). A study from Taiwan showed that 6–10 months IFN therapy in HBeAg(–) CHB patients had an end-of-treatment Therapeutics and Clinical Risk Management 2007:3(4)