title: Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Suh Sang
authors.initials: SS
authors.lastname: Jun
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Keum
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yeon Seok
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yim
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Yoon Tae
authors.initials: YT
authors.lastname: Jeen
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hoon Jai
authors.initials: HJ
authors.lastname: Chun
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hong Sik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Soon Ho
authors.initials: SH
authors.lastname: Um
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Chang Duck
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Pathology, Korea University College of Medicine, Seoul, Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Won
authors.affiliation: Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ho Sang
authors.initials: HS
authors.lastname: Ryu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006512:Hepatitis B Core Antigens / Q000276:immunology / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000276:immunology / Q000378:metabolism*; D006513:Hepatitis B e Antigens / Q000276:immunology / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine
keywords: Hepatitis B; Hepatitis B core antigens; Hepatitis B surface antigens; Histologic activity index; chronic