Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients

Abstract

Background/aims: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB).

Methods: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system.

Results: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05).

Conclusions: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.

Keywords: Hepatitis B; Hepatitis B core antigens; Hepatitis B surface antigens; Histologic activity index; chronic.

Fig. 1

Kaplan-Meier curve analysis in hepatitis B e antigen (HBeAg)-positive patients. (A) Cumulative incidence of HBeAg seroclearance (Kaplan-Meier plot) according to the histologic activity index (HAI; score ≥9) and presence of hepatocyte hepatitis B core antigen (HBcAg) expression. (B) Cumulative incidence of HBeAg seroclearance according to the HAI (score ≥9) and presence of hepatocyte HBcAg expression in patients with low alanine aminotransferase (ALT; <80 IU/L) levels. (C) Cumulative incidence of significant hepatitis B surface antigen (HBsAg) reduction according to the presence of hepatocyte HBcAg expression.

Fig. 2

Yearly mean hepatitis B surface antigen (HBsAg) reduction among patients followed up for 3 years.