title: Clinical significance and evolution of hepatic HBsAg expression in HBeAg-positive patients receiving interferon therapy.
abstract: BACKGROUND
  Serum hepatitis B surface antigen (HBsAg) level is important in the management of chronic hepatitis B (CHB). However, it is unclear whether serum HBsAg reflects its expression in liver and the hepatic HBsAg evolution following interferon therapy.
  
  
  METHODS
  Forty-five HBeAg-positive CHB patients receiving interferon-based therapy within a randomized, controlled, multicenter study during 1998-1999 were included. The hepatic HBsAg expressions were categorized into cytoplasmic, inclusion, marginal and negative patterns by immunohistochemical staining. The HBsAg-positive hepatocytes were quantified by image-based cytometry and correlated to HBV serological and virological profiles for clinical implications. The evolution of hepatic HBsAg levels was analyzed among 22 patients with paired liver biopsies before and after interferon therapy, sequentially.
  
  
  RESULTS
  There was a positive correlation between pretreatment serum HBsAg and hepatic HBsAg levels (r = 0.67, P < 0.0001). The hepatic HBsAg expression pattern significantly evolved from cytoplasmic/inclusion pattern to marginal/negative pattern after interferon treatment. The serum HBV-DNA, HBsAg and hepatic HBsAg levels all decreased significantly after interferon therapy. Among 36 % patients with HBeAg loss after therapy, pretreatment hepatic HBsAg levels were significantly lower compared with those without HBeAg loss. After multivariate analysis, low pretreatment hepatic HBsAg levels rather than serum HBsAg titers were associated with a higher rate of HBeAg loss (OR: 4.97, 95 % CI: 1.12-22.00, P = 0.035).
  
  
  CONCLUSIONS
  The serum HBsAg level positively reflects the HBsAg level in liver which evolves significantly after interferon therapy. A lower hepatic HBsAg level is associated with HBeAg loss after interferon treatment. Hepatic HBsAg may have clinical significance in CHB patients receiving interferon treatment.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei, 10002, Taiwan.
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Huei-Ru
authors.initials: HR
authors.lastname: Cheng
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.forename: Thai-Yen
authors.initials: TY
authors.lastname: Ling
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000032:analysis* / Q000097:blood; D006513:Hepatitis B e Antigens / Q000032:analysis*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000737:chemistry*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000410:Alanine Transaminase