Long Term Efficacy Of Entecavir Monotherapy In Chronic Hepatitis B Patients With Detectable Hbv DNA At 48 Weeks Of Entecavir Treatment

Background:The efficacy of continuous entecavir (ETV) therapy in patients with detectable HBV DNA at 48 weeks is still controversial.Aim:To compare the long term continuous efficacy of ETV in chronic hepatitis B (CHB) patients with detectable hepatitis B virus (HBV) DNA after 48 weeks versus undetectable patients, and to explore the predictive factors of maintained virologic response at 192 weeks of ETV therapy.Methods:This was a retrospective cohort study included CHB patients with ETV naive treated at least 48 weeks. Partial virologic response (PVR) was defined as a more than 1 loglOcopy/mL decline from baseline and detectable HBV DNA at week 48. Complete virologic response (CVR) was defined as undetectable HBV DNA within 48 week. Maintained virologic suppression was defined as undetectable HBV DNA until the last visit. Cumulative probability was evaluated by Kaplan-Meier analysis. Cox regression analysis was used to evaluate the associated factors with maintained virologic response.Results:A total of 259 patients were included. The median duration of treatment was 192(min 60-max 520) weeks. At week 48, the rate of PVR was 67 (25.9%). The baseline HBV DNA in the PVR group (8.72±0.89 log10copies/ml) was higher than that of CVR group (7.60±1.17 log10 copies/ml/ml), and the difference had statistical significance (P<0.05). Of the PVR patients, the cumulative probability of maintained virological suppression at week 48、96、144 and 192 weeks were 10.45%,45.20%, 72.30%,91.69%, respectively, by Kaplan-meier analysis, which were significantly lower than that of CVR group at each time points (P<0.05). By multivariate cox analysis, baseline HBV DNA level (Hazard ratio [HR],-0.16; 95% confidence interval [CI],0.76 to 0.97; p=0.02), and undetectable serum HBV DNA at week 48 (HR,1.57; 95% CI,3.17 to7.32; p<0.05) were found to be independently associated with maintained virologic suppression. The cumulative rates of virologic breakthrough were significant higher in patients with PVR than that of CVR group (p=0.01), but the genetic resistance had no difference. Among patients with HBeAg positive,62 patients in CVR group achieved HBeAg seroconversion compared with 13 patients in PVR group. The cumulative probability of HBeAg seroconversion in former group was superior to that of the latter group, with p value was 0.04. Among patients with HBeAg negative, baseline HBV DNA in PVR group was higher than that of CVR group (P<0.05). Then the baseline HBV DNA was categorized as high group (≥7log10copies/ml) and low group (< 7log10copies/ml). The cumulative probability of maintained virologic response in high group was less than that of low group (p<0.05).Conclusions:The ETV monotherapy could be effective in patients with a PVR, but had an increases risk of virologic breakthrough. The baseline HBV DNA and CVR were two predictive factors to the maintained virologic response. CVR patients with HBeAg positive had more likelihood to HBeAg seroconversion. For HBeAg negative patients, the PVR patients with baseline HBV DNA>7log10copies/ml had better to adjust the antiviral therapy.