Pretreatment HBeAg level and an early decrease in HBeAg level predict virologic response to entecavir treatment for HBeAg‐positive chronic hepatitis B

Abstract

There are few reports on hepatitis B e antigen (HBeAg) titres during nucleos(t)ide analogues treatment. We investigated the changes in HBeAg levels in patients treated with entecavir and the usefulness of HBeAg quantification for predicting antiviral response. Ninety-five consecutive HBeAg-positive patients treated with entecavir for more than 48 weeks were enrolled. Serum levels of hepatitis B surface antigen (HBsAg), HBeAg and HBV DNA were assessed at 4-week intervals to week 24 and thereafter at 12-week intervals. Virologic response (Y1VR) was defined as an undetectable HBV DNA level at week 48 of therapy. During 48 weeks, HBeAg and HBV DNA level decreased significantly in a biphasic manner and HBsAg level tended to decease. Fifty-three patients (55.8%) attained Y1VR. Pretreatment HBeAg levels were significantly lower in the Y1VR group than in no Y1VR group. At week 4 and 12 of therapy, 25% and 41.4% of patients showed a decrease of HBeAg levels with >0.5 log(10) and >1.0 log(10) from baseline, respectively. These patients achieved more Y1VR than those with less decrease of HBeAg levels (97.7%vs 22.2% and 86.2%vs 29.3%, respectively). HBeAg level at week 12 had higher predictive values for Y1VR than HBV DNA level. Multivariate analysis revealed that a pretreatment HBeAg level of <360 PEIU/mL and the reduction in HBeAg level >1.0 log(10) at week 12 were associated with Y1VR. These results suggest that pretreatment HBeAg level and an early decrease in HBeAg level are useful measurements for predicting one-year virologic response during entecavir treatment.

Efficacy of tenofovir disoproxil fumarate therapy in Chinese chronic hepatitis B patients after multiple antiviral failures

“…These results were consistent with a recent study showing that a 24-month TDF therapy induced satisfactory CVR (96.6%) in 29 NA failure patients. 10 Although it was considered that early serum HBsAg or HBeAg drop was a predictor of sustained virological response to PEG IFN and NA, 23,24 application of TDF in an NA therapy failure patient or new HBV infection patient needs further studies to identify its antiviral efficacy and prediction. In this study, HBsAg values were decreased, while CVR and ALT normalization rates were increased in all patients during the TDF therapy.…”

On-treatment quantitative hepatitis B e antigen predicted response to nucleos(t)ide analogues in chronic hepatitis B

“…However, other studies showed that pre-treatment serum HBeAg was associated with HBeAg SC during ETV treatment[10,12]. The inconsistent results may due to that treatment period was relatively short or HBeAg was detected semi-quantitatively in the latter’s studies[10,12].…”

“…Several studies tried to investigate the value of an early on-treatment change of HBV markers such as HBeAg in predicting VR to NAs therapy. A study presented that the HBeAg titer decreased by 1 lg PEIU/mL at 12-wk predicted VR (HBV DNA < 20 IU/mL) after 48-wk entecavir (ETV) therapy with a sensitivity, specificity, PPV, NPV of 67.6%, 87.9%, 86.2% and 70.7%, respectively[10]. However, the predictive value of HBeAg titer and its declined value at 12-wk for a long-term treatment response (≥ 2 years) was not reported.…”

“…However, other studies showed that pre-treatment serum HBeAg was associated with HBeAg SC during ETV treatment[10,12]. The inconsistent results may due to that treatment period was relatively short or HBeAg was detected semi-quantitatively in the latter’s studies[10,12]. Several recent studies revealed that B lymphocytes played a key role in the regulation of host immune responses to HBV, while anti-HBc was produced and secreted by hepatitis B core antigen-specific B lymphocytes, therefore the serum anti-HBc level may be a surrogate marker for the host immune response to HBV[16,17].…”

“…However, HBV DNA levels and its declines would not associate with 96-wk VR and HBeAg SC anymore if all parameters including HBeAg levels and its declines were enrolled in multivariate analysis. Other studies also pointed out that HBeAg levels as well as its declines may maintain a better predictive value than HBV DNA to predict NAs treatment response in HBeAg-positive CHB patients[10,11]. HBeAg is generated by transcription and translation of HBV cccDNA, and previous studies had reported that serum HBeAg level was significantly correlated with intrahepatic HBV cccDNA ( r = 0.507, P = 0.010)[22].…”