Complex HBV populations with mutations in core promoter, C gene, and pre-S region are associated with development of cirrhosis in long-term renal transplant recipients

Hepatology. 2002 Feb;35(2):466-77. doi: 10.1053/jhep.2002.30698.


Long-term immunosuppressed renal transplant recipients with chronic hepatitis B virus (HBV) infection often develop liver cirrhosis (LC) and end-stage liver disease (ESLD). This study investigated accumulation and persistence of specific HBV mutants in relation to the clinical course in these patients (n = 38; mean follow-up, 3.5 years). HBV was analyzed longitudinally via length polymorphism of polymerase chain reaction (PCR) fragments (median, 6.5 serum samples per patient) as well as by cloning and partial sequencing of 346 full-length HBV genomes. Fourteen patients (group 1) developed LC or died from ESLD, whereas 24 patients (group 2) showed no evidence of LC during follow-up. Development of LC and ESLD was associated with persistence of HBV mutant populations characterized by deletions/insertions in core promoter plus deletions in the C gene and/or deletions in the pre-S region (86% of group 1 vs. 17% of group 2; P <.0001). HBV without these mutations or with core promoter mutations alone were predominantly found in group 2 (14% of group 1 vs. 75% of group 2). In patients infected with core promoter mutants, the additional appearance and persistence of deletions in the C gene and/or the pre-S region were accompanied or followed by development of LC and ESLD. The mutations were distributed on individual genomes in various combinations, leading to a high complexity of the virus population. In conclusion, these data suggest that accumulation and persistence of specific HBV populations characterized by mutations in 3 subgenomic regions play a role in pathogenesis of LC and ESLD in long-term renal transplant recipients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Deletion
  • Genome, Viral
  • Hepatitis B / complications*
  • Hepatitis B / physiopathology
  • Hepatitis B / virology
  • Hepatitis B virus / genetics*
  • Humans
  • Kidney Transplantation*
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics*
  • Time Factors
  • Viral Core Proteins / genetics*


  • Viral Core Proteins