One study has shown the development of anti-HBs to have no influence Vorinostat in vivo over the subsequent occurrence

of HCC.4 Besides providing important clinical data on serologic and virologic parameters before spontaneous HBsAg seroclearance, our present study also offers a reference for future studies investigating the usefulness of serum HBsAg measurements of CHB patients undergoing antiviral therapy. Serum HBsAg levels have already been shown to be useful in predicting favorable outcomes in Peg-IFN therapy.28, 29 In contrast, patients commenced on nucleoside analog therapy do not show significant decline in serum HBsAg up to 2 years,30 although a 0.5-log reduction in HBsAg is also predictive of subsequent HBsAg seroclearance.31 The achievement of low HBsAg levels or a strong reduction in HBsAg should thus be investigated in the future for suitability as treatment endpoints. Future studies should also consider matching baseline HBsAg and HBV DNA levels for a more detailed comparison of HBsAg kinetics. A limitation of our study is that our patient population might not be totally representative of all treatment-naïve CHB populations, with no

HBeAg-positive patients at initial presentation included. Although HBsAg loss is possible shortly after HBeAg seroconversion,16 the average age of HBeAg seroconversion in our population is 35 years32 and the average age of HBsAg seroclearance is 50 years4; hence, the proportion LY294002 manufacturer of patients with HBsAg seroclearance within 3 years of HBeAg seroconversion is likely to be small. Therefore, the validity of our study results, when applied to spontaneous HBsAg

seroclearance, should not be affected by the absence of HBeAg-positive patients. In addition, HBV genotyping was not performed in all patients. Nevertheless, the lack of significant difference in genotype distribution among the two patient groups is in line with findings suggesting HBV Racecadotril genotypes as not being a key factor in determining HBsAg seroclearance.16 Further studies on this aspect are needed. In conclusion, in CHB patients with spontaneous HBsAg seroclearance, low levels of serum HBsAg could be detected up to 3 years before HBsAg seroclearance and were more predictive of HBsAg seroclearance than low levels of serum HBV DNA. Serum HBsAg levels <200 IU/mL already offered a good prediction of eventual HBsAg seroclearance in 3 years. In patients with serum HBsAg ≥200 IU/mL, an annual 0.5-log reduction in serum HBsAg increases the prediction of HBsAg seroclearance. Both absolute and serial measurements of serum HBsAg would offer valuable clinical data in determining the probability of long-term seroclearance. These may also serve as good indicators for the consideration of treatment duration and cessation for CHB. Additional Supporting Information may be found in the online version of this article.