title: 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.
abstract: 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.
authors.affiliation: Institut für Virologie, Humboldt-Universität zu Berlin (Charité), Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Preikschat
authors.forename: Stephan
authors.initials: S
authors.lastname: Günther
authors.forename: Simone
authors.initials: S
authors.lastname: Reinhold
authors.forename: Hans
authors.initials: H
authors.lastname: Will
authors.forename: Klemenz
authors.initials: K
authors.lastname: Budde
authors.forename: Hans H
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Detlev H
authors.initials: DH
authors.lastname: Krüger
authors.forename: Helga
authors.initials: H
authors.lastname: Meisel
mesh_terms: D000328:Adult; D005260:Female; D017353:Gene Deletion; D016679:Genome, Viral; D006509:Hepatitis B / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013997:Time Factors; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D014758:Viral Core Proteins