HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma

Gastroenterology. 2008 Oct;135(4):1192-9. doi: 10.1053/j.gastro.2008.07.008. Epub 2008 Jul 16.

Abstract

Background & aims: Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance.

Methods: We determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n = 229), liver histology, serum HBV DNA levels over time (n = 265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression.

Results: The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages >or=50 years compared with those with HBsAg seroclearance at ages <50 (P = .004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement (P = .001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5-10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels.

Conclusions: HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asians / statistics & numerical data*
  • Carcinoma, Hepatocellular / ethnology*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology*
  • Child
  • Child, Preschool
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Hepatitis B Antibodies / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B virus / isolation & purification*
  • Hepatitis B, Chronic / ethnology*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology
  • Hong Kong / epidemiology
  • Humans
  • Infant
  • Liver / pathology
  • Liver / virology
  • Liver Cirrhosis / ethnology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology
  • Liver Neoplasms / ethnology*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Risk Factors
  • Seroepidemiologic Studies

Substances

  • DNA, Viral
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens