Gut Liver.  2017 May;11(3):417-425. 10.5009/gnl16148.

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

• Yim SY
• Kim TH
• Jun SS
• Kim ES
• Keum B
• Seo YS
• Yim HJ
• Jeen YT
• Chun HJ
• Lee HS
• Um SH
• Kim CD
• Won NH
• Ryu HS

• KMID: 2412216
• DOI: http://doi.org/10.5009/gnl16148

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.

Keyword

Hepatitis B, chronic; Hepatitis B core antigens; Hepatitis B surface antigens; Histologic activity index

MeSH Terms

Adult
Antiviral Agents/therapeutic use
Biomarkers/analysis
Biopsy
Female
Guanine/analogs & derivatives/therapeutic use
Hepatitis B Core Antigens/immunology/*metabolism
Hepatitis B Surface Antigens/immunology/*metabolism
Hepatitis B e Antigens/immunology/metabolism
Hepatitis B virus/*immunology
Hepatitis B, Chronic/drug therapy/*immunology/virology
Hepatocytes/*immunology/virology
Humans
Liver/immunology/pathology/virology
Male
Middle Aged
Retrospective Studies
Treatment Outcome
Antiviral Agents
Biomarkers
Hepatitis B Core Antigens
Hepatitis B Surface Antigens
Hepatitis B e Antigens
Guanine