Background/Aims Decay of hepatitis B surface area antigen (HBsAg) titers has previously been shown to be predictive of a virologic response (VR), especially during peginterferon-alpha therapy. real-time PCR assay (<60 IU/mL). Results Fifty-two patients were enrolled, and the median duration of treatment was 26 months (range 7-35 months). Forty-five patients achieved a VR; the cumulative VR rates at 3, 6, 12, and 24 months were 40%, 71.2%, 81.5%, and 88%, respectively. Baseline HBV DNA levels were significantly lower in patients with VR, whereas the HBsAg amounts didn't differ between sufferers with or without VR significantly. Within a univariate evaluation the cumulative VR price was considerably higher in HBeAg harmful sufferers and sufferers with an Rabbit Polyclonal to CHRNB1 HBsAg/HBV DNA proportion above 0.56. Nevertheless, within a multivariate evaluation just an HBsAg/HBV DNA ratio above 0.56 was an independent predictor of VR (addresses the null hypothesis 2292-16-2 IC50 that the area under the curve (AUC) is equal to 0.5. The HBsAg/HBV DNA ratio shows the best overall performance at … Conversation Previous 2292-16-2 IC50 studies showed that on-treatment decline of HBsAg titer can predict VR during peg-IFN15-17 or NA therapy.18,20,21 However, it is not established whether pretreatment HBsAg levels can predict VR to antiviral drugs. It is controversial whether baseline HBsAg titer is usually a predictor of sustained response after peg-IFN therapy.16,17,24 Lee et al reported that low baseline HBsAg levels were associated with VR to entecavir in HBeAg-positive CHB,21 whereas another report showed no significant association of pre-treatment HBsAg levels with response to telbivudine.18 Our data also revealed no significant association between pre-treatment HBsAg levels and VR (P=0.278; Table 2). In contrast, we found that serum HBsAg/HBV DNA ratio predict VR better than HBsAg level or HBV DNA level in nucleos(t)ide na?ve CHB patients treated with entecavir (P<0.05; Fig. 3). Recent reports have exhibited that serum HBsAg levels vary among different stages in the natural history of CHB. HBsAg level is the least expensive in the low replicative phase compared to immune tolerance, immune clearance phase and HBeAg unfavorable hepatitis phase.25,26 Moreover, HBsAg production does not change in parallel with HBV DNA across the natural history of CHB.27 Serum 2292-16-2 IC50 HBsAg/HBV DNA ratio is higher in the low-replicative phase compared to immune-tolerant, immune-clearance and HBeAg negative hepatitis phase.25,26 Dissociation between HBV DNA and HBsAg levels may be caused by 1) HBsAg production from integrated viral genome in low-level HBV replication stage, or 2) preferential control of HBV replication by cytokine effects.27 In either case, high HBsAg/HBV DNA 2292-16-2 IC50 ratio may indicate enhanced host immunity which preferentially suppresses HBV replication pathway (transcription of pregenomic RNA), relatively sparing HBsAg transcription.27,28 If this hypothesis is true, then it is feasible that this enhanced host immunity may help to control HBV replication below undetectable level during entecavir therapy, leading to more frequent VR. We have previously reported that pre-treatment serum HBV DNA level is usually a predictor of virologic response after entecavir therapy,14 and cohort in this paper included part of the prior research subjects. Nevertheless, baseline HBV DNA was predictive of VR after two years of entecavir therapy with just marginal statistical significance (P=0.059; Fig. 2), because of smaller sized test size within this research probably. There is wide overlap of HBV DNA amounts between VR (+) and VR (-) groupings, whereas HBsAg/HBV DNA ratios can better differentiate both groups on the cut-off worth of 0.56 by ROC evaluation (Fig. 3). As this scholarly research enrolled limited amounts of sufferers, baseline HBV DNA amounts could also have already been a predictor of virologic response if more sufferers have been enrolled. Further research is certainly warranted to validate the superiority of HBsAg/HBV DNA proportion over HBV DNA level with bigger sample size and longer duration of treatment. HBsAg levels tend to become higher in HBeAg-positive CHB compared to HBeAg-negative CHB in earlier studies,25,26 whereas the difference was not significant in our data (P=0.071; Table 1). The study from Asia reported that HBsAg levels are genotype-dependent25: the difference in HBsAg levels tend to become smaller between immune clearance and HBeAg-negative CHB in genotype C which is the unique genotype in Korea. Interestingly, the HBsAg/HBV DNA ratios of immune clearance (HBeAg-positive) and HBeAg-negative CHB in our study are nearly identical to the people from those earlier studies,25,26 recommending that marker could be reproducible of ethnicity or genotypes regardless. Our data implies that pre-treatment HBsAg/HBV DNA proportion over 0.56 may predict long-term virologic response (threat proportion=2.239, P=0.003; Desk 3). Pre-treatment predictor (HBsAg/HBV DNA proportion) may possess clinical benefit over on-treatment HBsAg level adjustments in predicting VR because various other powerful NA (eg. tenofovir) could be attempted in sufferers who’ve low pre-treatment possibility of VR to entecavir. As our research has not examined on-treament HBsAg adjustments, this presssing issue ought to be elucidated in further studies. To conclude, pre-treatment serum HBsAg/HBV DNA proportion can predict long-term VR.