title: Hepatitis B virus core promoter mutations in patients with chronic hepatitis B and hepatocellular carcinoma in bucharest, romania.
abstract: BACKGROUND
  Accurate and personalized molecular virological diagnosis of hepatitis B virus (HBV) infection is crucial for individualized selection of patients for antiviral therapy in Romania.
  
  
  OBJECTIVE
  We aimed to investigate HBV mutations in Romanian patients with chronic HBV infection, also to match HBV genotypes with HBV mutations identified and clinical outcomes.
  
  
  METHODS
  This was a cross-sectional study. A total of 484 Romanian patients with chronic HBV infection and hepatocellular carcinoma (HCC) were investigated. This was performed in Fundeni Clinical Institute, Bucharest, Romania during January 2005 to August 2010. HBsAg positive patients with chronic HBV infection admitted to Fundeni Clinical Institute were randomly enrolled in the study. Analysis was performed in the Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania. Indirect diagnosis was performed with enhanced chemiluminescence method using Architect i2000SR and HBV-DNA was quantified with COBAS TaqMan HBV PCR. Direct sequencing of the PCR-products was performed with the PCR-product sequencing kit. HBV genotyping was performed with INNO-LiPA DR Amplification and INNO-LiPA HBV precore-core.
  
  
  RESULTS
  We detected two HBV genotypes; A (8.1%) and D (60.5%), and a mixture of genotypes A and D (31.4%) (P < 0.001). Basal core promoter (BCP) A1762T/G1764A and precore (PC) G1896A mutations were detected in these Romanian patients with chronic HBV infection. HBV chronic carriers had mainly genotype D (54.4%) and HBV WT (64.0%). BCP A1762T, G1764A and PC G1896A were significantly associated with HCC-tissue HBV sequencing (75.3%) (P < 0.001). PC G1896A alone was detected in HCC-serum HBV sequencing group (66.7%).
  
  
  CONCLUSIONS
  Genotype D was the main genotype detected in Romanian patients with chronic HBV infection. Genotype D presented both BCP and PC mutations more frequently.
authors.affiliation: Immunology of Transplantation Discipline, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania ; Center for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Ileana
authors.initials: I
authors.lastname: Constantinescu
authors.affiliation: Center for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Andrei-Antoniu
authors.initials: AA
authors.lastname: Dinu
authors.affiliation: "Gheorghe Mihoc-Caius Iacob" Institute of Statistics and Applied Mathematics, Bucharest, Romania.
authors.forename: Voicu
authors.initials: V
authors.lastname: Boscaiu
authors.affiliation: Colentina Clinical Hospital, Bucharest, Romania.
authors.forename: Marius
authors.initials: M
authors.lastname: Niculescu
keywords: Genotype; Hepatitis B Virus; Hepatocellular carcinoma; Mutations