Hepatitis B surface antigen: relation to hepatitis B replication parameters in HBeAg-negative chronic hepatitis B

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Hepatitis B surface antigen (HBsAg) translation relies on cccDNA transcription, but its serum level determinants, including integrated HBV-DNA, are unclear in HBeAg-negative chronic hepatitis B (CHB).
• Understanding HBsAg serum level correlations is crucial for managing CHB patients.

Purpose of the Study:

• To investigate the relationship between serum HBsAg levels and hepatocellular HBsAg expression.
• To explore the association of serum HBsAg with hepatitis B virus (HBV) replication parameters (cccDNA, liver HBV-DNA, serum HBV-DNA) and host response (ALT).
• To assess the impact of nucleoside/nucleotide (NUC) therapy on these parameters.

Main Methods:

• Studied 54 HBeAg-negative CHB patients before and 15 after NUC therapy.
• Quantified liver cccDNA and HBV-DNA, and performed HBsAg/HBcAg immunostaining on liver biopsies.
• Measured serum HBsAg and HBV-DNA levels concurrently with liver biopsies.

Main Results:

• In untreated patients, serum HBsAg correlated with HBsAg-positive hepatocytes and weakly with serum HBV-DNA, but not cccDNA or liver HBV-DNA.
• cccDNA significantly correlated with liver HBV-DNA, ALT, and serum HBV-DNA.
• NUC therapy significantly reduced serum HBsAg (79.6%) and liver HBV-DNA (84.4%), but not cccDNA.

Conclusions:

• Serum HBsAg levels in untreated HBeAg-negative CHB reflect liver HBsAg expression but not cccDNA or liver HBV-DNA levels.
• These findings suggest serum HBsAg is not solely dependent on the HBV replicative cycle.
• Sustained NUC therapy effectively lowers serum HBsAg and liver HBV-DNA, highlighting its role in managing CHB, although cccDNA remains unaffected.