Dimou et al has been reported in 15%–25% of patients treated for 6 or more months with a signiﬁcant percentage of them (31.6%) also loosing HBsAg (Hadziyannis et al 1990; Manesis and Hadziyannis 2001; Papatheodoridis et al 2001). On the other hand PEG-IFN-α-2a either alone or in combination with LAM in HBeAg-positive CHB, achieved similar rates of HBeAg seroconversion in 32% and 27% of patients, respectively and both regimens were superior to LAM monotherapy (32% vs 19%, p 0.001 and 27% vs 19%, p = 0.02) (Lau et al 2005) (see also Figure 1). In HBeAg- negative CHB, PEG-IFN-α-2a alone or in combination with LAM achieved similar rates of virologic remission (HBV-DNA 20.000 cp/mL) in 43% and 44% of patients, respectively and again the two regimens were clearly supe- rior to LAM monotherapy (29%, p = 0.007 and p = 0.003, respectively) (Marcellin et al 2004). Furthermore, follow-up of patients, 2 years after discontinuation of treatment has shown that the response appears to be durable (Marcellin et al 2006). Treatment with PEG-IFN-α-2a is probably superior to standard IFN-α, but there is no comparative study between the two forms of interferon-α applied in courses of the same duration. Although treatment with IFN-αs has many adverse events and the disadvantage of subcutaneous administration, these are the only available drugs that can achieve HBsAg seroconversion in ﬁnite courses of treatment of less than one year duration (Wong et al 1993; Marcellin et al 2004; Lau et al 2005). In view of the above data it is clear that both in HBeAg- positive and HBeAg-negative patients with chronic hepatitis B pegylated IFN-α2a monotherapy in ﬁnite courses of 48 weeks % HBeAg seroconversion Log HBV DNA reduction 12 3,6 ADV 18 4 LAM 21 6,9 ETV duration, achieves higher rates of responses sustained after their discontinuation compared to LAM monotherapy. Lamivudine Lamivudine, the ﬁrst licensed nucleoside analogue (Lai et al 1998; Dienstang et al 1999), may achieve HBeAg seroconver- sion, in 18% of HBeAg-positive CHB patients at the ﬁrst year and in 27% and 40% at the second and third year respectively (Lai et al 1998; Dienstang et al 1999; Liaw et al 2000; Leung et al 2001). In HBeAg-negative CHB, LAM therapy for one year resulted in undetectable serum HBV DNA in 65% of patients (Tassopoulos et al 1999). The high rate of virologic response at one year is not sustainable after discontinuation of therapy, while prolongation of treatment is associated with decreasing rates of virologic response due to the emergence of LAM-resistant HBV mutants in progressively increasing rates reaching levels above 60% in 4 to 5 years time (Lai et al 1998; Dienstang et al 1999; Liaw et al 2000; Leung et al 2001; Papatheodoridis et al 2002; Lok et al 2003). The develop- ment of viral resistance may be associated with worsening of liver histology, exacerbation of liver disease and even with liver failure and deaths especially in patients with cirrhosis (Dienstag et al 2003; Lok et al 2003; Di Marco et al 2004; Liaw et al 2004; Papatheodoridis et al 2005). Adefovir dipivoxil Adefovir dipivoxil, a nucleotide analogue, the second licensed oral anti-HBV agent, is effective in the treatment of both wild type and LAM-resistant HBV (Hadziyannis et al 2003; Marcellin et al 2003; Peters et al 2004). 32 23 6,5 5,8 LdT PegIFN Figure 1 Comparison of responses to treatment (HBeAg seroconversion and log reduction of serum HBV DNA) of HBeAg positive chronic hepatitis B. Lau et al. 2005. N Engl J Med, 352:2682–95. Dienstag et al. 1999. N Engl J Med, 341:1256–63. Marcellin et al. 2005. EASL, Abstract 73. Lai et al. 2005. AASLD, Abstract 72404.(LB1) Chang et al. 2004 AASLD,Abstract 70.Telbivudine package insert. Marcellin et al. 2003. N Engl J Med. 348:808–16. Chang et al. 2006. N Engl J Med. 354:1001–10. 1078 Therapeutics and Clinical Risk Management 2007:3(6)