response of 57% (vs 18% of controls) and 6 months sustained response of 30% (vs 7%) (Lin et al 2001). However, therapeutic effect of IFN-α2b in Asian patients has been far inferior to the results seen among European patients, possibly related to a longer duration of infection (Asians are often infected perinatally) and different HBV genotypes. Lok et al (1988) reported that IFN-α2b has little long-term effect in suppressing HBV replication in Chinese patients with CHB. Interestingly, Martin et al (1998), in their prospective controlled study with IFN-α2b comparing Caucasian and Asian-American patients with CHB, found no difference in clearance of HBeAg loss or HBV DNA (62% vs 60%) except for a shorter durability of response in Asian- American patients. The Asian American patients in this study were noted to have acquired HBV infection during adulthood. Side effect of IFN-α2b include ﬂu-like symptoms, depression, renal failure, heart failure, and alopecia and others. Pegylated interferon-α Recently, pegylated forms of IFN-α2a (PegIFN-α2a) have been developed. Because of a decreased renal clearance rate, PegIFN-α2a is administered weekly. Studies suggest that PegIFN-α2a is more effective than standard IFN-α. The side effect proﬁle of PegIFN-α2a is similar to that of standard IFN-α. PegIFN α2a in doses of 180 µ g weekly has been used for 48 weeks in both HBeAg(–) (Lau et al 2005) and HBeAg(–) CHB (Marcellin et al 2004). The major- ity of 814 HBeAg(+) patients studied by Lau et al (2005) were Asian (87%). Most of them were infected with HBV genotype B or C. At the end of 48 week treatment, HBeAg seroconversion occurred in 27% of patients, and increased to 32% at the end of 6-month post-treatment observation period (Lau et al 2005). For HBeAg(–) 537 CHB patients, PegIFN-α2a in doses of 180 µ g weekly for 48 weeks with or without LVD produced better results (HBV DNA decrease, ALT normalization) than LVD alone at the end of 6 months follow up off treatment (Marcellin et al 2004). Nucleos(t)ide analogues LVD, ADV, entecavir (ETV) and telbivudine (LdT) are all orally administered drugs currently available for treatment of CHB. In addition, several candidates, such as emtricitabine, clevudine, TDF, pradefovir and others are in the ﬁnal stages of clinical trials. Lamivudine (LVD) LVD is a potent inhibitor of viral replication, convenient to administer, and has very few side effects. LVD is given in Therapeutics and Clinical Risk Management 2007:3(4) Time for an active therapy for HBV a dose of 100 mg (or 150 mg) daily. For HBeAg(+) CHB, a 2 year course of LVD has resulted in further increase of HBeAg seroconversion from 17% at 1 year to 27% at 2 years (Liaw et al 2000) and 47% after 4 years (Chang et al 2004). With LVD therapy, the majority of patients develop unde- tectable HBV DNA by PCR assay. However, LVD therapy should be continued until HBeAg seroconversion which may take months to years even after HBV DNA has become undetectable. The optimal duration of LVD administration following HBeAg seroconversion remains undetermined at present time. Nonetheless, it has generally been agreed that it needs to be longer than 6 months due to frequent relapses observed after cessation of therapy. The half-life of HBV- infected hepatocytes is reported to be 10–100 days with a mean of 16 days (Nowak et al 1996) and Zeuzem et al (1997) in their study with LVD described that the half life of HBV infected cells is longer than 100 days and 1 year treatment of LVD will not reduce the number of infected cells to less than 10% of its initial value. Ryu et al (2003) reported results of their study in which patients were continued on LVD therapy for 6, 12 and 24 months after the HBeAg conver- sion. They observed relapse rates 2 years after the cessation of LVD therapy to be 57%, 51% and 29% of patients who received 6, 12 and 24 months of additional LVD therapy respectively. More importantly, if LVD is stopped before HBeAg seroconversion even with undetectable HBV DNA, virus returns often accompanied with ALT ﬂare which can be severe at times. For HBeAg(–) patients, the length of continued therapy is determined from the time point when HBV DNA becomes undetectable by the available PCR assay. Currently, the rec- ommendation is to continue treatment for minimum 2 more years after HBV DNA becomes undetectable. Despite this, there are relapses even after completion of the recommended length of therapy. Therefore, the efﬁcacy of life-long treat- ment for the management of HBeAg(–) CHB is currently under investigation (Perrillo 2006). Although it has been well established that HBeAg loss correlated positively with pretreatment ALT levels (Perrillo et al 2002) in LVD therapy, other studies with LVD (Hann et al 2005) and ETV (Rosmawati et al 2003), did not ﬁnd signiﬁcant correlation between pretherapy ALT and the virological response. Hann et al (2005) compared LVD therapy results for 317 HBeAg(+) and HBeAg(–) CHB patients with active viral replication with regard to differ- ent pretreatment ALT levels (upper normal limit of ALT 40 U/L). In this study, the loss of HBeAg were 40%, 57% and 61% for groups with pretreatment ALT upper limit 607