Also, the decision to discontinue therapy should not be postponed because the prediction of SR did not improve significantly at week 24 compared to week 12. The kinetics of serum HBsAg and HBV DNA levels clearly differed during the treatment phase. HBV DNA levels decreased throughout the entire treatment period, whereas a later decline was observed

in serum HBsAg levels. HBsAg and HBV DNA levels were not correlated ALK inhibitor at the baseline and early during the treatment phase, and this further underlined the additional value of HBsAg levels in the prediction of SR. The added information that is provided by a quantitative assessment of serum HBsAg may be explained by the dual antiviral and immunomodulatory mode of action of peginterferon. The on-treatment reduction in serum HBV DNA primarily reflects the direct antiviral effect of peginterferon. In contrast, the decline in serum HBsAg may be selleck kinase inhibitor a marker of its immunomodulatory effects, which result in gradual clearance of infected hepatocytes from the liver through the induction of cytotoxic T cell activity.27 In line with these findings, it has been demonstrated that reductions in serum HBsAg mirror the decline in intrahepatic cccDNA.13, 14 Recently, high predictive values

for on-treatment HBsAg declines at weeks 12 and 24 with respect to sustained virological response (HBV DNA <70 copies/mL) were reported in a cohort of 48 patients treated with peginterferon alfa-2a for 48 weeks.17 This finding was not confirmed HSP90 in our larger study population, which was derived

from a randomized controlled trial. This discrepancy may be generated by the substantial difference in response rates between the two studies. In the study by Moucari et al.,17 25% of patients developed a sustained virological response. This response rate is substantially higher than that in any peginterferon study for HBeAg-negative patients and suggests that a selection bias may have affected the results of this retrospective study. In our study, SR had previously been defined as the combined presence of a serum HBV DNA level <10,000 copies/mL and a normal ALT level at 6 months after treatment discontinuation. One could argue that the HBV DNA threshold should have been set at a lower level. Indeed, the off-treatment undetectability of serum HBV DNA by a sensitive polymerase chain reaction assay is a major virological endpoint and is strongly associated with HBsAg clearance from serum in the years afterward.28 However, these preferred treatment endpoints occur infrequently in HBeAg-negative patients treated with peginterferon. In fact, another important goal of therapy for HBeAg-negative CHB is the induction of the HBsAg inactive carrier phase. Our endpoint of a serum HBV DNA level <10,000 copies/mL combined with a normal ALT level appears to differentiate reliably between inactive carriers and patients with HBeAg-negative CHB.