HBsAg and HBcrAg as predictors of HBeAg seroconversion in HBeAg‐positive patients treated with nucleos(t)ide analogues

Abstract

HBeAg seroconversion marks an important spontaneous change and treatment end-point for HBeAg-positive patients and is a pre-requisite for HBsAg loss or functional cure. In this retrospective analysis, we aimed to identify predictors of seroconversion using serum quantitative HBsAg and HBcrAg, in HBeAg-positive patients treated with nucleos(t)ide analogues (NA). Data and samples from 118 HBeAg-positive adults (genotypes A-G) started on NA between Jan 2005 and Sept 2016 were retrospectively analysed at several time-points. The predictive power of on-treatment levels of HBsAg and HBcrAg was determined using receiver operating curve (ROC) analysis and cut-off values determined by maximized Youden's index. About 36.4% of patients achieved HBeAg seroconversion after a median of 39 months' treatment. On treatment kinetics of HBV DNA, HBsAg and HBcrAg differed between HBeAg seroconverters and nonseroconverters. A combination of HBsAg and HBcrAg had the greatest predictive value for HBeAg seroconversion: at 6 months, HBsAg of 3.9 log IU/mL and HBcrAg of 5.7 log U/mL had a sensitivity of 71.4%, specificity of 79.5%, positive predictive value (PPV) of 65.2% and negative predictive value (NPV) of 83.8%, with AUROC of 0.769 (0.668, 0.869; 95%CI), and at 12 months, HBsAg 3.8 log IU/mL and HBcrAg 5.5 log U/mL had a sensitivity of 73.7%, specificity of 79.5%, PPV of 63.6% and NPV of 86.1%, with AUROC 0.807 (0.713, 0.901; 95% CI). In conclusion, our results may be used to identify patients who are unlikely to achieve treatment end-points, which will be important as the future management of chronic hepatitis B looks to therapies that offer functional cure.

Relationship between hepatitis B core‐related antigen levels and sustained HBeAg seroconversion in patients treated with nucleo(s)tide analogues

“…A recent study conducted with PEG-IFN treated patients suggested that serum HBcrAg levels could be used for prediction of sustained responses. 8,9 In our cohort, patients with lower baseline HBcrAg levels had a higher probability of HBeAg seroconversion. However, HBcrAg strongly correlated with other important factors, and the association of HBcrAg with HBeAg seroconversion was not sustained in multivariate analysis.…”

“…However, relapse rates are high and predictors of sustained response are not well established. A recent study conducted with PEG‐IFN treated patients suggested that serum HBcrAg levels could be used for prediction of sustained responses . In our cohort, patients with lower baseline HBcrAg levels had a higher probability of HBeAg seroconversion.…”

“…Recently, the novel biomarker hepatitis B core-related antigen (HBcrAg) has been shown to predict spontaneous HBeAg seroconversion, both in untreated patients, 7 and in patients treated with NUCs or peginterferon (PEG-IFN). 8,9 We aimed to investigate the relationship between (a) baseline HBcrAg levels and rates of HBeAg The study was conducted in accordance with the declaration of Helsinki. Patients enrolled in the ARES trial provided written informed consent.…”

“…So far, no factor has been identified that reliably predicts sustained HBeAg seroconversion in patients treated with NUCs. Recently, the novel biomarker hepatitis B core‐related antigen (HBcrAg) has been shown to predict spontaneous HBeAg seroconversion, both in untreated patients, and in patients treated with NUCs or peginterferon (PEG‐IFN) . We aimed to investigate the relationship between (a) baseline HBcrAg levels and rates of HBeAg seroconversion and (b) HBcrAg levels at the time of HBeAg seroconversion and subsequent relapse in HBeAg‐positive patients treated with NUCs.…”

New viral biomarkers for Hepatitis B: Are we able to change practice?

“…log10 IU/mL and HBcrAg of 5.7 log10 U/mL had a PPV of 65.2% and NPV of 83.8% for HBeAg seroconversion. 74 Given these findings, it is likely that the combination of HBV RNA, HBcrAg and HBsAg may be used in the future as predictors for patients, who achieve favourable endpoints.…”