The expression of hepatitis B spliced protein (HBSP) encoded by a spliced hepatitis B virus RNA is associated with viral replication and liver fibrosis

J Hepatol. 2003 Mar;38(3):343-8. doi: 10.1016/s0168-8278(02)00422-1.


Background/aims: We have previously demonstrated the in vivo expression of a new spliced hepatitis B virus (HBV) protein (HBSP) encoded by a singly spliced pregenomic RNA. The present study was designed to evaluate the impact of HBSP expression on the clinical status and liver pathology of HBV infection.

Methods: Sera from 125 chronic HBV carriers were tested for the presence of HBSP antibodies by an indirect enzyme-linked immunosorbent assay test. The severity of liver damage was evaluated using the Knodell score.

Results: Anti-HBSP antibody prevalence in HBV chronic carriers was 46%. We highlighted the concomitant expression of HBSP protein and anti-HBSP antibody. An association between anti-HBSP antibody detection and serum markers of HBV replication was demonstrated. With respect to HBV-related liver disease, an association was only observed with the severity of fibrosis. Furthermore, an elevation of secreted tumor necrosis factor alpha (TNFalpha), but not of soluble TNFalpha receptor 75, was observed in anti-HBSP-antibody-positive patients. Multivariate analysis showed that anti-HBSP antibody detection was independently associated with viral replication, severity of fibrosis and elevated TNFalpha secretion.

Conclusions: Our data suggest the hypothesis that HBSP might play a role in the natural history of HBV infection and may be involved in the pathogenesis and/or persistence of HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / analysis
  • Carrier State
  • Female
  • Gene Expression*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • RNA Splicing*
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Proteins / genetics*
  • Viral Proteins / immunology
  • Virus Replication / genetics*


  • Antibodies, Viral
  • HBSP protein, Hepatitis B virus
  • Tumor Necrosis Factor-alpha
  • Viral Proteins