Non-F HBV/HDV-3 coinfection is associated with severe liver disease in Western Brazilian Amazon.

The clinical outcome of hepatitis B virus (HBV) infection may be related to host and viral genetic factors, as well as to the type of infection (monoinfection and coinfection). To analyze the distribution/combination of HBV/hepatitis D virus (HDV) genotypes and the associated clinical characteristics, 409 serum samples from patients with chronic HBV (94 of them coinfected by HDV) followed at the Viral Hepatitis Referral Center of Rio Branco, Brazil were enrolled. HBV DNA and HDV RNA were amplified, respectively, by polymerase chain reaction (PCR) and nested PCR using specific primers in the PreC/C region and the S gene, and by reverse-transcription PCR and seminested PCR using specific primers in the delta antigen region and sequenced. The proportion of women (56.1%) was significantly higher than males in this cohort ( P < 0.01). Women were significantly younger (39.8 years; 8-77 years) than males (44.7 years; 12-79 years; P < 0.01). Sixty-eight (18%) patients were infected with HBV-F genotype and 264 (69.8%) with HBV/non-F genotypes. Coinfection by HDV was detected in 23.9% (94 of 409) of this population and was more frequent in male (54.2%, 51 of 94) than in female patients (44.7%, 42 of 94; P = 0.015). HDV-3 was the most prevalent (88.9%) genotype. Almost 70% of HDV-3 coinfected patients were infected with HBV/non-F genotypes. Severe liver disease was diagnosed in 41 patients, 60.9% (25 of 41) of them coinfected with HDV. HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels. HBV/HDV-3 coinfection is associated with severe liver disease, in Rio Branco, Brazil.

Identification of novel recombinants of hepatitis B virus genotypes F and G in human immunodeficiency virus-positive patients from Argentina and Brazil.

Hepatitis B virus (HBV) genotype G (HBV/G) infection is almost always detected along with a co-infecting HBV strain that can supply HBeAg, typically HBV/A2. In this study we describe, in two human immunodeficiency virus (HIV)-positive patients from Argentina and Brazil, the first report of HBV/G infection in Argentina and co-circulation of HBV/G, HBV/F and G/F recombinants in the American continent. HBV isolates carrying the 36 bp insertion of HBV/G were the most prevalent in both patients, with >99 % of colonies hybridizing to a probe specific for this insertion. Phylogenetic analyses of full-length genomes and precore/core fragments revealed that F4 and F1b were the co-infecting subgenotypes in the Brazilian and Argentinian patients, respectively. Bootscanning analysis provided evidence of recombination in several clones from both patients, with recombination breakpoints located mainly at the precore/core region. These data should encourage further investigations on the clinical implications of HBV/G recombinants in HBV/HIV co-infected patients.

Hepatitis B virus infection from an evolutionary point of view: how viral, host, and environmental factors shape genotypes and subgenotypes.

Hepatitis B virus (HBV) has an overwhelming distribution in the world and causes important human health problems. It has infected one-third of the global population and more than 350 million people are chronic carriers. Several aspects of HBV infection confer adaptive advantages that lead to a highly efficient dissemination of the virus through different routes of transmission. HBV genotypes and subgenotypes have been associated with differences in clinical and virological characteristics, indicating that they may play a role in the virus-host relationship. In particular, a clear association between genotype A and chronic outcomes in both children and adults depending on the subgenotype involved, and between genotype C and a higher risk of complications from HBV infection, has been demonstrated. Interestingly, subgenotype A2 and genotype C are respectively likely to predominate in high-risk groups for sexual transmission and in areas where perinatal transmission is the major mode of HBV dissemination. An evolutionary approach to HBV infection, based on the principles of natural selection, may offer explanations for how modes of transmission may favor some genotypes and subgenotypes over others and, ultimately, influence HBV virulence.

Virological and histological re-evaluation of Labrea hepatitis.

BACKGROUND: a peculiar form of fulminant hepatitis known as Labrea hepatitis, probably related to hepatitis B and D, has been reported in Brazilian Amazon as early as the 1930s. METHODS: we reviewed the postmortem liver biopsies of 9 patients with Labrea Hepatitis. Immunostaining for HBV and HDV antigens were performed. RESULTS: we found several important characteristics in the liver tissues: 1) moderate hepatocellular necro-inflammation, 2) hepatocellular ballooning, 3) ballooned hepatocytes with fat droplets surrounding the nucleus (morula-like cells or spongiocytes), 4) mild to moderate necrosis and/or mild portoseptal fibrosis. Hepatitis B surface antigen (HBsAg) was identified in 7 of the 9 cases and was concentrated in the Morula-like cells. Hepatitis B core antigen (HBcAg) was present in 5 cases, mostly in the hepatocyte's nucleous. The hepatitis D virus antigen (HDV Ag) was present in 5 cases, mostly in the cytoplasm and concentrated in the Morula-like cells. CONCLUSION: labrea hepatitis is a fatal disease mostly affecting isolated communities in the Amazon. Evidence implicates HBV and HDV in the etiology of this disease, but this hypothesis needs to be confirmed with genotyping and sequencing research on HBV DNA and HDV RNA extracted from the liver and sera of these patients.

HDV genotypes in the Western Brazilian Amazon region: A preliminary report.

In Brazil, hepatitis delta virus (HDV) is only reported in Western Amazonia, where severe cases of acute and chronic HDV hepatitis have been described. The study area was chosen in the States of Acre and Rondonia where most cases of hepatitis B virus (HBV)/HDV are reported. From December 2003 to October 2004, 40 HBsAg carriers with anti-HDV IgM were selected. An epidemiologic questionnaire, including demographic and clinical/epidemiologic variables was filled out. HDV amplification and genotyping were performed. Genotype I was detected in 22 patients (55.0%), whereas genotype III was identified in 18 (45.0%). Patients who were infected with genotype I were older (45.1 +/- 17.8 years) than patients infected with genotype III (32.8 +/- 10.9 years; P = 0.01). No symptoms were reported by 21 (52.5%) patients. Otherwise, 19 (47.5%) had symptoms (fatigue, abdominal pain, weight loss, and decompensated liver disease) that motivated them to seek medical care. Genotype III carriers were more symptomatic, but no statistical significance was achieved. Our preliminary results show that HDV genotypes I and III are present in Brazilian Amazonia and that HDV genotype III is not limited to the Amerindian population.