Others have also reported associations with qHBeAg and clinical responses or virological breakthrough in patients treated with LAM and PEG-IFN.17, 19-21 Most recently, a thorough investigation that included both qHBsAg and qHBeAg was conducted to identify their relationship with intrahepatic markers of HBV replication, and it suggested potential practical implications for these quantitative serological markers.24

Our study is the first to report serial qHBeAg values in patients on ETV therapy. We have shown that a decline in qHBeAg is highly predictive for SR with sensitivity and specificity values as high as 75.0% and 89.8%, respectively. Selleck AT9283 In other words, if a 10-fold drop in qHBeAg is encountered with 6 months of ETV therapy, there is a good chance of SR in such patients. Recent investigations have alluded to a potentially interesting aspect of qHBsAg as antigen expression in the natural course of HBV infection. Two independent groups found that the level of qHBsAg Crizotinib mouse was higher in the immune-tolerant and immune-clearance phases

than in the low-replicative phase and in patients with HBeAg(−) disease.22, 23 These discrepancies in qHBsAg across different phases of CHB infection and in correlation between qHBsAg and HBV DNA provide evidence that different pathways exist for HBsAg and HBV DNA production as well as that HBV may integrate into the host genome. In addition, similar published results have demonstrated 上海皓元 a good correlation in HBeAg(+) patients (r = 0.69, P < 0.001), whereas the association between HBsAg production and HBV replication broke down in HBeAg(−) patients (r = 0.28, P = 0.012); this was assumed to occur when HBsAg was produced from a source other than cccDNA.24 These reports suggest that the correlation between qHBsAg and HBV DNA without antiviral treatment is more significant in the higher HBV replicative phase

than in the low-replicative phase. As expected, our study on patients receiving ETV demonstrated a significant correlation between HBV DNA and qHBsAg only in HBeAg(+) patients. This correlation coefficient peaked at 6 months and gradually decreased over time. A possible explanation for this is that the proportion of patients with undetectable or lower HBV DNA levels increased with ETV therapy, and this led to a similar status for the low-replicative phase. Moreover, a modest decline of qHBsAg during ETV therapy could not catch up with the rapid reduction of HBV DNA, and the result was the disproportional status of these two parameters. This explanation, however, warrants further validation because the dynamic relation between qHBsAg and HBV DNA should be understood in the context of overproduction of defective HBsAg particles and the role of integrated HBV DNA.30 Some limitations of this study need consideration. First, only Korean patients with genotype C HBV were included in this study. Although homogeneity in a study population is in some ways favorable, it limits generalization.