title: Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase.
abstract: In view of the findings that high hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is associated with increased risk of chronic hepatitis B (CHB)-related complications, disease progression in CHB patients in the immune-tolerant phase is uncertain. We evaluated disease progression in 57 immune-tolerant CHB patients with high HBV DNA. Each subject underwent an initial liver biopsy. In those who remained in the immune-tolerant phase, a follow-up liver biopsy was performed after 5 years of follow-up. Patients who developed elevated serum alanine aminotransferase (ALT) levels were discontinued from the study after a follow-up liver biopsy. Disease progression was defined as a 1-point increase in fibrosis stage. Initial liver biopsies showed the median fibrosis stage of the study patients was 1 (range 0-1). By the end of follow-up, 9 of the 57 patients (15.8%) had developed elevated serum ALT. In those who remained in the immune-tolerant phase, follow-up fibrosis stage was comparable with the initial fibrosis stage (P = 0.58). However, disease progression was greater in patients who developed elevated serum ALT when compared with those who remained in the immune-tolerant phase (5 of 9 vs. 3 of 48, respectively, P = 0.001). The median rate of fibrosis progression of patients who remained in the immune-tolerant phase was lower than that of patients with high serum ALT (0 U/year [range -0.40-0.20 U/year] versus 0.21 U/year [range 0-1.11 U/year], respectively, P = 0.04).
  
  
  CONCLUSIONS
  CHB patients in the immune-tolerant phase have mild disease. In those who remained in the immune-tolerant phase in the present study, disease progression was minimal. However, immune-tolerant patients who progressed to the immune clearance phase often faced disease progression.
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong Special Administrative Region (SAR), China. ckhui23@gmail.com
authors.forename: Chee-Kin
authors.initials: CK
authors.lastname: Hui
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.forename: Siu-Tsan
authors.initials: ST
authors.lastname: Yuen
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: Kar-Wai
authors.initials: KW
authors.lastname: Leung
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.forename: Stephen K F
authors.initials: SK
authors.lastname: Cheung
authors.forename: Wai-Man
authors.initials: WM
authors.lastname: Wong
authors.forename: George K
authors.initials: GK
authors.lastname: Lau
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D008099:Liver / Q000473:pathology; D008297:Male
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase