title: The precore mutation is associated with severity of liver damage in Brazilian patients with chronic hepatitis B.
abstract: BACKGROUND
  The clinical relevance of the G1896A precore mutation in chronic hepatitis B is still poorly understood.
  
  
  OBJECTIVE
  To assess the frequency of G1896A precore mutation in Brazilian patients with chronic hepatitis B, as well as its relation to the viral genotype, serum HBV-DNA levels and liver damage.
  
  
  METHODS
  Fifty chronic hepatitis B patients (29 HBeAg-negative and 21 HBeAg-positive) were studied. HBV-DNA was quantified by the Amplicor HBV Monitor test and precore region and S gene were amplified and submitted to automatic sequencing. The histological activity index (HAI), degrees of hepatic fibrosis and distribution of core antigen (HBcAg) in hepatocytes were determined.
  
  
  RESULTS
  Precore mutation occurred in 1/21 (4.8%) HBeAg-positive patients and in 17/29 (58.6%) HBeAg-negative (p < 0.0001). Genotype D was identified in 56.5%, genotype A in 41.3%, and genotype F in 2.2%. The frequency of genotypes D and A, as well as serum levels of ALT and HBV-DNA were similar in patients infected with wild type and with precore mutant. Patients infected with precore mutant presented a higher frequency of moderate/severe HAI (p: 0.03) and moderate/severe fibrosis and cirrhosis (p: 0.03) than those infected with wild type. There was no association between G1896A mutation and cytoplasmic expression of HBcAg.
  
  
  CONCLUSIONS
  Precore mutation was frequent among Brazilian subjects with chronic hepatitis B and its presence was associated with greater severity of liver disease.
authors.affiliation: Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, FMRP-USP. 14048-900, Ribeirão Preto, SP, Brazil. rosamarrezende@uol.com.br
authors.forename: Rosamar E F
authors.initials: RE
authors.lastname: Rezende
authors.forename: Benedito A L
authors.initials: BA
authors.lastname: Fonseca
authors.forename: Leandra N Z
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Sérgio
authors.initials: S
authors.lastname: Zucoloto
authors.forename: João Renato R
authors.initials: JR
authors.lastname: Pinho
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Bertolini
authors.forename: Ana L C
authors.initials: AL
authors.lastname: Martinelli
mesh_terms: D001938:Brazil / Q000453:epidemiology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D009154:Mutation; D012720:Severity of Illness Index; D014758:Viral Core Proteins / Q000235:genetics*; D014766:Viremia / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral; D014758:Viral Core Proteins