Monitoring of Serum HBV RNA, HBcrAg, HBsAg and anti-HBc Levels in Patients during Long-Term Nucleoside/Nucleotide Analogue Therapy

Abstract

Background: This study was aimed at evaluating the clinical significance of serum HBV RNA, hepatitis B corerelated antigen (HBcrAg) and hepatitis B core antibody (anti-HBc) levels in chronic hepatitis B patients with undetectable HBV DNA during nucleoside/nucleotide analogue (NA) treatment. Methods: Fifty-seven patients who received long-term NA treatment of median 5.83 (25%, 75% percentiles 4.67, 7.75) years were enrolled, and 285 serum samples at five time points for each patient were quantitatively analysed for the three serum markers together with serum HBV DNA and hepatitis B surface antigen (HBsAg) levels. Results: The HBV RNA level significantly correlated with HBcrAg (r=0.629; P<0.001) but not HBsAg levels (P=0.1460). Nonetheless, the HBcrAg level significantly correlated with the HBsAg level (r=0.469; P<0.001). Hepatitis B e antigen (HBeAg)-positive samples showed higher HBV RNA, HBcrAg and HBsAg levels than HBeAgnegative samples did (all P<0.05). Nine patients with HBeAg loss manifested a significantly greater decline in HBV RNA and HBcrAg levels (median 1.84 [25%, 75% percentiles 1.02, 2.12] log 10 copies/ml, 1.14 [0.62, 2.21] log 10 U/ml, respectively) compared with those in seven patients without HBeAg loss (0.74 [0.10, 1.08] log 10 copies/ml and 0.41 [0.21, 0.69] log 10 U/ml, respectively). Overall, serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels gradually decreased with time during NA treatment. At the end of observation, HBV RNA and HBcrAg reached an undetectable level in 26 and 6 (46% and 11%) patients, respectively. Conclusions: Monitoring of HBV RNA and HBcrAg levels is useful for NA-treated patients with undetectable HBV DNA. The attainment of HBV RNA undetectability usually occurs prior to HBcrAg undetectability.

Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues

“…The decline of serum HBV RNA induced by NAs therapy and its underlying mechanism might be greatly different from the decline of serum HBV DNA. Several studies have reported that serum HBV RNA can remain higher than serum HBV DNA during long‐term NAs treatment of CHB patients 19,29‐31 . We also displayed this regular pattern of kinetics of HBV nucleic acids (Figure S3), and found that undetectable serum HBV RNA appeared after serum HBV DNA became undetectable during NAs therapy (Figure 2; Figure S4).…”

Kinetics of Hepatitis B Core–Related Antigen and Anti–Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus–Hepatitis B Coinfection

“…For qAnti-HBc antibodies, its kinetics in TDF-treated HIV-HBV coinfected patients showed a steady decline, for both HBeAg-positive or HBeAg-negative patients, similar to HBV mono-infected individuals treated with peg-IFN or NAs [19,31,32]. Interestingly, the observation of higher median baseline qAnti-HBc levels in HBeAg-negative versus HBeAgpositive patients could be the result of increased immune activity in patients previously able to clear HBeAg [33,34].…”

“…Others have found that qHBcrAg levels at week 12 of peg-IFN treatment were predictive of post-treatment HBeAg-seroclearance [29], while another study investigating entecavir (ETV) with or without peg-IFN add-on therapy observed that higher qHBcrAg levels at both week 24 and week 36 were independently associated with a lower risk of HBeAg-seroclearance and HBV-DNA suppression 24-weeks post-treatment in both treatment arms [37]. With regards to NA-based therapy, baseline HBcrAg levels >5.7 log10 U/mL have been also associated with lack of HBeAg-seroconversion at 6 and 12 months of treatment [28] and faster declines of qHBcrAg were observed in patients with HBeAg-seroclearance as compared to those without [33]. Our findings in TDF-treated HIV-HBV co-infected patients fall in line with these studies.…”

Role of Biomarkers in Guiding Cure of Viral Hepatitis B

“…65 A recent study investigating the dynamics of various HBV biomarkers in patients on NAs, has reported that HBV RNA is the first marker to become undetectable, followed by HBcrAg. 93 In that study, HBcrAg and HBV RNA were undetectable in 11 and 46% of patients, respectively, during 5 years of therapy. 93 Regarding NA discontinuation, low HBcrAg levels have been linked with a low risk of HBV reactivation.…”

“…93 In that study, HBcrAg and HBV RNA were undetectable in 11 and 46% of patients, respectively, during 5 years of therapy. 93 Regarding NA discontinuation, low HBcrAg levels have been linked with a low risk of HBV reactivation. 94,95 Recently, a score incorporating a combination of HBsAg and HBcrAg has been used to assess the risk of early and late clinical relapse, with good performance.…”