Tracing back hepatitis B virus genotype D introduction and dissemination in South Brazil.

Hepatitis B virus (HBV) infection is widespread and it is considered a major health problem in the world. HBV is classified into genotypes and subgenotypes. HBV genotype D (HBV-D) has been detected worldwide with high prevalence in some specific regions from Europe and South America. In Brazil, this genotype is very frequent in the South region and its introduction and dissemination have been associated with European immigration (mainly Italian). The present study aimed to trace back the introduction and dissemination of HBV-D in South Brazil. Fifty-two chronic hepatitis B patients from two cities with an early history of Italian immigration in South Brazil were selected for the present study. HBV-DNA was detected, quantified and a partial genomic region (S/P overlapped genes) was amplified by PCR and sequenced for the determination of HBV genotypes/subgenotypes. HBV complete genome sequences of some selected samples were further obtained. Bayesian coalescent analyses were performed to estimate the HBV-D evolutionary dynamics. Phylogenetic analysis demonstrated the occurrence of three genotypes according the tree topology: HBV-D (n = 49; 94.2%), HBV-A (n = 2; 3.9%) and HBV-G (n = 1; 1.9%). In addition, HBV-D presented three subgenotypes: HBV-D3 (n = 39; 79.6%), HBV-D2 (n = 8; 16.3%), and HBV-D1 (n = 2; 4.1%). The Bayesian coalescent analysis demonstrated that the HBV-D was introduced in the 20th century. HBV-D3 was the first to be introduced in South Brazil, probably between 1904 and 1942. HBV-D2 and HBV-D1 were introduced later; HBV-D2 between 1946 and 1953 and HBV-D1 between 1954 and 1969. HBV-D3 spread at a high rate from the 1920s to the 1980s, while HBV-D2 showed a slower growth from the 1960s to the 1990s and HBV-D1 infections demonstrated low and constant population size across time. After the 2000s, a stationary growth was detected for all these three-D subgenotypes. HBV-D showed a high prevalence in South Brazil and this is possibly associated with the first introduction and dissemination of HBV-D3 at the beginning of the 20th century.

Risk factors for hepatitis B transmission in South Brazil.

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem in Brazil. Several risk factors are involved in HBV infection and their identification by a rational and essential approach is required to prevent the transmission of this infection in Brazil. OBJECTIVES: To evaluate risk factors associated with HBV infection in South Brazil. METHODS: A total of 260 patients with HBV and 260 controls from Caxias do Sul (state of Rio Grande do Sul, Brazil) participated in this study. All participants were given a standard questionnaire to yield the sociodemographic information and to identify HBV risk factors. HBV infection was detected by HBsAg test in all participants. FINDINGS: HBV infection in these cases was strongly associated with history of a family member HBV-infected, mainly mother [odds ratio (OR) = 4.86; 95% confidence intervals (CI): 1.69-13.91], father (OR = 5.28; 95% CI: 1.58-17.71), and/or siblings (OR = 22.16; 95% CI: 9.39-52.25); sharing personal objects (OR = 1.40; 95% CI: 1.37-2.38); and having history of blood transfusion (OR = 2.05; 95% CI: 1.10-2.84). CONCLUSIONS: HBV infection was strongly associated with having a family member infected with hepatitis B, sharing personal objects, and having history of blood transfusion.

Risk factors for hepatitis B transmission in South Brazil

BACKGROUND Hepatitis B virus (HBV) infection is a major public health problem in Brazil. Several risk factors are involved in HBV infection and their identification by a rational and essential approach is required to prevent the transmission of this infection in Brazil. OBJECTIVES To evaluate risk factors associated with HBV infection in South Brazil. METHODS A total of 260 patients with HBV and 260 controls from Caxias do Sul (state of Rio Grande do Sul, Brazil) participated in this study. All participants were given a standard questionnaire to yield the sociodemographic information and to identify HBV risk factors. HBV infection was detected by HBsAg test in all participants. FINDINGS HBV infection in these cases was strongly associated with history of a family member HBV-infected, mainly mother [odds ratio (OR) = 4.86; 95% confidence intervals (CI): 1.69-13.91], father (OR = 5.28; 95% CI: 1.58-17.71), and/or siblings (OR = 22.16; 95% CI: 9.39-52.25); sharing personal objects (OR = 1.40; 95% CI: 1.37-2.38); and having history of blood transfusion (OR = 2.05; 95% CI: 1.10-2.84). CONCLUSIONS HBV infection was strongly associated with having a family member infected with hepatitis B, sharing personal objects, and having history of blood transfusion.

HBV carrying drug-resistance mutations in chronically infected treatment-naive patients.

BACKGROUND: Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. METHODS: HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. RESULTS: There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified subgenotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. CONCLUSIONS: HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.