title: Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance.
abstract: OBJECTIVE
  During the natural course of hepatitis B virus (HBV) infection, the long-term clinical and histological outcomes following spontaneous hepatitis B surface antigen (HBsAg) seroclearance remain unclear.
  
  
  METHODS
  Between 1984 and 2003, 49 (9.5%) out of 432 inactive HBsAg carriers had no detectable level of circulating HBsAg. Fifteen of 49 patients had undergone paired peritoneoscopic liver biopsies.
  
  
  RESULTS
  During a mean follow-up period of 19.6 months after HBsAg seroclearance, 5 of 49 (10.2%) patients were noted to have HCC. Liver cirrhosis (P=0.040), a history of perinatal infection (P=0.005) and long-standing duration (at least 30 years) of HBsAg positivity (P=0.002) were associated with a significantly higher risk of developing HCC. Despite HBsAg seroclearance, HBV DNA was detected in the liver tissues from all 15 patients who underwent paired liver biopsies. Necroinflammation was significantly ameliorated (P<0.0001). On the other hand, amelioration of the fibrosis score did not reach a statistically significant level (P=0.072). Interestingly, aggravation of liver fibrosis was evident in 2 patients (13.3%) including one who had rapidly progressed to overt cirrhosis.
  
  
  CONCLUSIONS
  In patients with spontaneous HBsAg seroclearance, necroinflammation was markedly improved and liver fibrosis was unchanged or regressed despite occult HBV infection. However, HCC developed in a minority of cases.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul, South Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Young Nyun
authors.initials: YN
authors.lastname: Park
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Chang
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Shin
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Chanil
authors.initials: C
authors.lastname: Park
authors.forename: Young Myoung
authors.initials: YM
authors.lastname: Moon
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
mesh_terms: D000328:Adult; D001483:Base Sequence; D002353:Carrier State / Q000097:blood; D017931:DNA Primers; D004279:DNA, Viral / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D006509:Hepatitis B / Q000097:blood / Q000473:pathology; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009336:Necrosis; D019562:Viral Load
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens