Predictive value of intrahepatic hepatitis B virus covalently closed circular DNA and total DNA in patients with acute hepatitis B and patients with chronic hepatitis B receiving anti-viral treatment

Abstract

This study aimed to investigate the persistence and predictive values of intrahepatic (IH) hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and total DNA (tDNA) in patients with acute hepatitis B (AHB) and patients with chronic hepatitis B (CHB) receiving anti‑viral treatment. The levels of IH cccDNA and tDNA, serum HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) were detected in 11 patients with AHB and 46 patients with CHB who were receiving anti‑viral treatment, among whom 21 had primary treatment failure, 11 achieved virological response (VR) and 15 achieved VR and HBsAg seroclearance. The median IH cccDNA and tDNA levels in the patients with AHB (0.002 copies/cell and 0.04 copies/cell, respectively) were significantly lower than those in the patients with CHB. In the patients with CHB, the median IH cccDNA level among individuals who achieved VR and HBsAg seroclearance (0.012 copies/cell) was significantly lower than that in those who had failed primary treatment (4.18 copies/cell, P<0.0001) but not that in those who achieved solely VR (0.039 copies/cell, P=0.169). The median IH tDNA level in patients with CHB who achevied VR and HBsAg seroclearance (0.096 copies/cell) was significantly lower than that in those who failed primary treatment (371 copies/cell, P<0.0001) and those who achieved solely VR (1.62 copies/cell, P=0.001). No significant difference was observed in the area under the receiver operating characteristic (ROC) curve, which was used to predict the likelihood of achieving VR and HBsAg seroclearance, between IH tDNA and IH cccDNA levels (0.96 and 0.88, respectively; P>0.10). IH cccDNA levels were shown to be positively correlated with serum ALT (P=0.024), HBeAg (P=0.001) and IH tDNA levels (P<0.0001), but not with serum HBV DNA (P=0.12) and HBsAg levels in either HBeAg‑positive (P=0.84) or in HBeAg‑negative (P=0.146) patients. In conclusion, IH cccDNA may persist in patients with AHB and patients with CHB who acheive VR and HBsAg seroclearance following anti‑viral treatment. Furthermore, IH cccDNA and tDNA may have potential in predicting successful therapeutic response in patients with CHB who receive anti‑viral treatment.

Different types of viral‑host junction found in HBV integration breakpoints in HBV‑infected patients

“…In the present study, this was demonstrated by the expression of chimera transcription of number 4, where the breakpoint of the inserted viral fragment was mapped in the S gene. This finding was also in accordance with a previous report, in which serum HBsAg and IH cccDNA levels were not correlated in patients with HBeAg-negative CHB (26), whereas patients with HBeAg-negative CHB usually have a longer, mostly perinatal HBV infection history and are expected to have more extensive HBV DNA integration than HBeAg-positive cases (27).…”

Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy–Experienced Patients in Europe (CAPRE)

“…Although there was no indication of previous LAM use in these patients, we cannot fully exclude the possibility of prior undisclosed treatment with LAM. As HBV can persist for long periods of time as covalently closed circular DNA (cccDNA), even during treatment and HBsAg seroclearance [35], the cccDNA reservoir can act as an archive of drugresistant viral strains [36]. Previous studies have shown that therapy failure of ETV is more likely to occur in patients previously carrying LAM-resistant viral strains even when resistance was no longer detectable after LAM interruption [37,38].…”

HoxA10 Facilitates SHP-1-Catalyzed Dephosphorylation of p38 MAPK/STAT3 To Repress Hepatitis B Virus Replication by a Feedback Regulatory Mechanism

“…7D), revealing that HoxA10 represses X promoter activation. The X promoter regulates HBx gene transcription, which potentiates HBV replication, regulates HBV oncogenicity, and affects multiple cellular functions (38)(39)(40)(41). We constructed the X/EnhI promoter and its five promoter-truncated mutants and then subcloned these constructs into the pGL3-Basic vector to generate six reporters (Fig.…”