title: Hepatitis B virus genotype distribution and genotype-specific BCP/preCore substitutions in acute and chronic infections in Argentina.
abstract: OBJECTIVE
  In order to assess Hepatitis B Virus genotype (g) and subgenotype (sg) implications in the course of infection, 234 HBsAg positive patients in different infection stages were characterized (66 acute infections, 63 HBeAg positive chronic infections and 105 anti-HBe positive chronic infections).
  
  
  RESULTS
  Overall, sgA2 (17.9%), gD (20.9%), sgF1b (34.2%) and sgF4 (19.7%) were the most prevalent. Subgenotype F1b was overrepresented in acute and chronic HBeAg infections (56.1%), whereas gD was the most frequent (40.0%) in anti-HBe positive chronic infections. Among chronic infections, HBeAg positivity rates were 50.0, 12.5, 62.8 and 35.3% for sgA2, gD, sgF1b and sgF4, respectively (p <0.05). A bias toward BCP/preCore mutations was observed among genotypes. In anti-HBe positive chronic infections, sgF1b was more prone to have A1762T/G1764A mutation than sgA2, sgF4 and gD (75.0, 40.0, 33.3 and 31.8%, p<0.005), whereas in the pC region, gD and sgF4 were more likely to have G1896A than sgA2 and sgF1b (81.0, 72.7, 0.0 and 31.3%, p <0.001). The unexpected low frequency of the G1896A mutation in the sgF1b (despite carrying 1858T) prompted us to perform a further analysis in order to identify genotype-specific features that could justify the pattern mutations observed. A region encompassing nucleotides 1720 to 1920 showed the higher dissimilarity between sgF1b and sgF4. Genotypes and subgenotypes carrying the 1727G, 1740C and 1773T polymorphisms were prevented to mutate position 1896.
  
  
  CONCLUSIONS
  HBeAg seroconversion is a critical event in the natural history of HBV infection. Differences in the HBeAg positivity rate might be relevant since different studies have observed that delayed HBeAg seroconversion is associated with a more severe clinical course of infection, highlighting the critical role that genotypes/subgenotypes might play in the progression of HBV infection. Polymorphisms in the regions 1720 to 1920 could be involved in the molecular mechanisms underlying seroconversion of each genotype/subgenotype.
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: María Mora
authors.initials: MM
authors.lastname: González López Ledesma
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Laura Noelia
authors.initials: LN
authors.lastname: Mojsiejczuk
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Belén
authors.initials: B
authors.lastname: Rodrigo
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Ina
authors.initials: I
authors.lastname: Sevic
authors.affiliation: Unidad de Hepatología, Hospital de Infecciosas "F. Muñiz," Buenos Aires, Argentina.
authors.forename: Lilia
authors.initials: L
authors.lastname: Mammana
authors.affiliation: Unidad de Hepatología, Hospital Italiano Buenos Aires, Buenos Aires, Argentina.
authors.forename: Omar
authors.initials: O
authors.lastname: Galdame
authors.affiliation: Unidad de Hepatología, Hospital Italiano Buenos Aires, Buenos Aires, Argentina.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gadano
authors.affiliation: Unidad de Hepatología, Hospital de Infecciosas "F. Muñiz," Buenos Aires, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fainboim
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Campos
authors.affiliation: Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Flichman
mesh_terms: D000704:Analysis of Variance; D001118:Argentina / Q000453:epidemiology; D001483:Base Sequence; D003430:Cross-Sectional Studies; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D013045:Species Specificity
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