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

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.

Relationship between Intrahepatic Expression of Hepatitis Be Antigen and Histology in Patients with Hepatitis B Virus Infection / 대한내과학회지

BACKGROUND: It has been known that the sero- logic markers of infectivity and viral replication in patients with hepatitis B virus(HBV) infection are hepatitis B e antigen(HBeAg), HRV DNA and HBV DNA polymerase. METHODS: In order to clarify the relationship between chronic liver diseases and HBV infection, and the mechanism of chronicity in HBV related liver diseases, the expression patterns of hepatic HBeAg by imrnunohistochemical stain and histologic activity index(HAI) were studied from 10% formalin fixed paraffin embedded tissues in 114 patients performed liver biopsy. RESULTS: The results were as follows: 1) Incidence of serum HReAg positivity in HBsAg positive patients was 74.6% and that of hepatic HBeAg expression was 77.6% among serum HBeAg positive cases. Hepatic HBeAg expression was 72.4% in serum HBeAg negative cases. 2) In serum HBeAg positive cases, almost all infected hepatocytes exhibited cytoplasmic HBeAg expression and half of patients showed nuclear HBeAg expression, but cytoplasmic HBeAg expression was solely predominant in serum HBeAg negative cases. Hepatic HBeAg expression showed a decreasing trend from AVH and CPH, through CAH, to cirrhosis with or without HCC, which was a consistent finding with serum HBeAg in decreasing manner. Hepatic HBeAg expreassion was highly sustained in about 60-90% of cases, regardless of duration of their illnesses. 3) HAI showed slighf3y higher tendency in patients with hepatic HBeAg negative expression than in positive cases. CONCLUSION: The above results suggest that HBeAg may play a role as a viral target antigen for immune-mediated liver injury and may be also related to the pathogenetic mechanism of chronicity in chronic hepatitis B.