Clonal analysis of hepatitis B viruses among blood donors from Joinville, Brazil: Evidence of dual infections, intragenotype recombination and markers of risk for hepatocellular carcinoma

Abstract

Hepatitis B virus (HBV) is classified into seven major genotypes (A-H). Brazil, a country of continental proportions, has three prevailing lineages of HBV genotypes A, D, and F. Distinct HBV genotypes have been associated with differential risk of disease progression. Pre-S gene deletions and single nucleotide polymorphisms have also been linked to progression to liver diseases. In this study, the molecular epidemiology of HBV was examined in Southern Brazil. The occurrence of multiple HBV infections, HBV recombination, and genetic markers of disease progression were also evaluated. Seventy-eight persons infected with HBV had their viruses characterized molecularly by nested PCR, DNA sequencing, and phylogenetic inference. Multiple infections and recombinant viruses were evaluated by clonal and bootscanning analyses. The vast majority (96%) of the strains belonged to different D subgenotypes. Three of the four strains with unresolved genotypic classification showed evidence of dual infections with distinct D subgenotypes by clonal analysis. There was also evidence of intragenotype mosaic viruses. While four viruses had pre-S deletions as major variants, another two displayed minor variants with such characteristics. One strain carried the F141L mutation, associated recently with increased risk of hepatocellular carcinoma. These results emphasize the need for monitoring HBV genotype distribution around South America, as well as for the presence of genetic markers of disease progression in subjects diagnosed with HBV recently.

Seroprevalence of Hepatitis B and C markers at the population level in the municipality of Caxias do Sul, southern Brazil

“…In a previous Brazilian retrospective study, 61% of HCV positive patients were male, differing from the findings of the present study, where occurrence of females was of 52.4%(Reis et al , 2011). This seropositivity could be attributed to the fact that the population of female attends more regularly to medical services than men, HCV infection usually runs in a subclinical fashion, showing no symptoms in the early years after contact with the virus, where approximately 70–85% of patients develop persistent infection and asymptomatic, developing over a long period of time chronic hepatitis, and hepatic cirrhosis (Focaccia and Oliveira, 2010).…”

“…Lower rates of prevalence (< 2%) are often reported in North America, Western Europe and Australia (Abbas and Siddiqui, 2011; Bertolini et al , 2012; Fonseca, 2010). This may be influenced by several aspects, including the presence of certain viral genotypes, which are also correlated to the ethnic groups living in a given geographic region (Bertolini et al , 2012; Reis et al , 2011). …”

“…The southern region has a low to intermediate endemicity, with an increasing trend to reach the North, which has the highest percentage of infected individuals in the country (Anastácio et al , 2008; Aquino et al , 2008; Bertolini et al , 2012; Ladehof and Bueno, 2005; Reis et al , 2011). The seroprevalence rates in the country for HBV are ranging from 1.9% to 13.5%, and the rates found on the present study are slightly below this range, with an overall seropositivity of 1.63%.…”

“…Until the year 1992 the anti-HCV assay were not carried out as a screening test for blood transfusions and blood products, and probably at that time this may be main mode of transmission of HCV. Vaccination against HBV in Brazil only began in the mid 1990’s on children and only later was extended to adolescents and individual on risk groups (Reis et al , 2011). …”