Association of hepatitis B virus pre-S deletions with the development of hepatocellular carcinoma in chronic hepatitis B

J Infect Dis. 2011 Mar 1;203(5):646-54. doi: 10.1093/infdis/jiq096. Epub 2011 Jan 12.

Abstract

Background: We aimed to determine whether hepatitis B virus (HBV) pre-S deletion was an independent factor for the development of hepatocellular carcinoma (HCC).

Methods: Pre-S deletions were determined in HBV isolates from 115 chronic hepatitis B (CHB) patients with HCC. Sixty-nine patients were further matched with 69 CHB patients without HCC for age, sex, hepatitis B e antigen (HBeAg) status, and HBV genotype.

Results: HBV pre-S deletions were clustered mainly in the 3' end of pre-S1 and 5' end of pre-S2 regions. Adjusted for confounding risk factors, patients with HCC had a higher prevalence of HBV with pre-S deletions than did patients without HCC (23 [33.3%] of 69 vs 11 [15.9%] of 69; P = .018; odds ratio [OR], 2.64). In particular, only pre-S2 deletions but not pre-S1 deletions were significantly associated with the development of HCC (P = .020). A higher prevalence of pre-S deletions was observed in HBV isolates from HCC patients under the age of 50 years than from those older than 50 years (10 [62.5%] of 16 vs 13 [24.5%] of 53; P = .012; OR, 5.13). Emergence of de novo pre-S deletions was documented before the development of HCC.

Conclusions: HBV pre-S2 deletions were an independent factor associated with the development of HCC. Its oncogenic role may be more important in young patients with HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology*
  • Case-Control Studies
  • DNA Primers
  • Databases, Nucleic Acid
  • Female
  • Gene Deletion*
  • Genotype
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B virus / chemistry
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / genetics
  • Hepatitis B, Chronic / virology*
  • Hong Kong / epidemiology
  • Humans
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Mutation
  • Polymerase Chain Reaction
  • Protein Precursors / chemistry
  • Protein Precursors / genetics
  • Risk Factors
  • Sequence Alignment

Substances

  • DNA Primers
  • Hepatitis B Surface Antigens
  • Protein Precursors