Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection

Gastroenterology. 2002 Oct;123(4):1084-9. doi: 10.1053/gast.2002.36026.


Background & aims: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance is a rare event in patients with chronic hepatitis B virus infection. The aim of this study was to clarify the controversy on long-term prognosis following spontaneous HBsAg seroclearance using a large series of patients.

Methods: A total of 218 patients (172 men and 46 women) who had undergone spontaneous HBsAg seroclearance were followed up for 12-179 months (median, 61.7 months; mean, 63.4 +/- 38.5 months) with liver biochemistry, serology, measurement of alpha-fetoprotein level, and abdominal ultrasonography every 6 months or every 3 months for the 29 patients who had developed cirrhosis at the time of HBsAg seroclearance.

Results: Of the 189 patients who were noncirrhotic at the time of HBsAg clearance, 3 (1.6%) developed cirrhosis, 2 (1.1%) developed hepatocellular carcinoma (HCC), and 1 died of HCC. These complications all developed in patients with concurrent hepatitis C virus or hepatitis delta virus infection (P < 0.001). The prognosis of the noncirrhotic patients without concurrent infection was significantly better than that of the matched control group (elevation of alanine aminotransferase level, 11.6% vs. 0%, P < 0.001; development of cirrhosis/HCC, 4% vs. 0%, P = 0.004). In contrast, of the 29 patients who had developed liver cirrhosis, 4 (13.8%) had hepatic decompensation and one died of HCC.

Conclusions: The prognosis following spontaneous HBsAg seroclearance is excellent, except in patients with cirrhosis or those with concurrent hepatitis C virus or hepatitis delta virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / virology
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / complications
  • Hepatitis C Antibodies / blood
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / complications
  • Hepatitis D, Chronic / blood
  • Hepatitis D, Chronic / complications
  • Humans
  • Liver Cirrhosis / virology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Prognosis


  • Hepatitis B Surface Antigens
  • Hepatitis C Antibodies