In contrast, the American Association for the Study of Liver Diseases (AASLD)2 and Asian Pacific Association for the Study of the Liver (APASL)3 guidelines view “durable” HBeAg seroconversion as an adequate end-point. The APASL guidelines also specify that the

HBeAg seroconversion should be accompanied by undetectable HBV DNA. However, the question remains whether treatment-induced HBeAg seroconversion together with virological response is truly durable. Even with pegylated interferon therapy, in a 5-year long-term follow-up study, selleck inhibitor despite the cumulative incidence of HBeAg seroconversion of up to 60%, only 29% of patients had HBV DNA <20 000 IU/mL, and 13% had HBV DNA <20 IU/mL.4 With lamivudine (LAM), an early study of 34 Korean patients who stopped LAM after HBeAg seroconversion showed a cumulative relapse rate of 49% after 2 years.5 Another study of 82 patients

from Taiwan showed that 48% had relapsed by 12 months, with genotype C infections being associated with higher rates of relapse.6 A study of 132 Korean patients reported a relapse rate of 66% at 12 months after stopping LAM.7 A more recent Korean study of 178 patients who stopped LAM after achieving HBeAg seroconversion showed selleck kinase inhibitor a lower relapse rate of 30% at 5 years.8 In 125 Chinese patients who stopped LAM after HBeAg loss or seroconversion, the 4-year cumulative relapse (defined as serum HBV DNA ≥ 2000 IU/mL) rates were 41% and 29%, respectively.9 Common to all these studies is the fact that older age and shorter duration of consolidation therapy after HBeAg seroconversion are associated with higher rates of relapse. However, it is important to note carefully the definition of relapse in the different studies. The low 5-year relapse rate of 30% in the previously-described study is likely due to the high cut-off level of >28 000 IU/mL used to define the reappearance of HBV DNA. When virological rebound was defined strictly as a 1 log increase in HBV DNA, the virological rebound rate was 82% at 4 years in a study of 22 patients

who stopped LAM after HBeAg seroconversion. Seventy-eight percent of patients had undetectable HBV DNA at the time of last follow up in those who continued with LAM, compared to 0% in those who stopped (P < 0.001).10 Altogether, these studies show that off-treatment response after HBeAg seroconversion is not durable. An argument can be medchemexpress made for those in the younger age group in whom antiviral therapy might be stopped with a lower risk of relapse after an extended consolidation treatment period. However, there is no agreement as to the acceptable age cut-off and the length of consolidation. Soo et al. reported a 31% cumulative relapse rate after 2 years following LAM cessation in 85 CHB patients who had received at least 24 months of consolidation.11 For HBeAg-negative patients, both the EASL and AASLD guidelines recommend that treatment should be continued until HBsAg clearance is achieved.