Overt and occult hepatitis B virus infection among treatment-naïve HIV-infected patients in Brazil.

Although hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection is common, only few data are available on HBV among HIV patients including occult hepatitis B infection (OBI), regardless of serological markers. This study aims to determine the prevalence of OBI and overall HBV infection, associated factors, HBV genotypes, and surface (S) gene mutations in a population of treatment-naïve HIV-infected patients in Brazil. A cross-sectional study was conducted in treatment-naïve HIV-infected patients in Central Brazil. All samples were tested for HBV serological markers and HBV DNA. Sequence analysis of the S gene and overlapping polymerase gene was preformed. Overall, 25.1% (127/505) of the patients had markers of current or previous HBV infection, which was associated with age over 40 years, history of injection drug use, and homosexual sex. The hepatitis B surface antigen (HBsAg) seroprevalence was 4.9% (25/505). HBV DNA was detected in 39 out of 505 patients: 20 of them were HBsAg-positive and 19 were HBsAg-negative, resulting in an OBI prevalence of 3.8%. Patients with OBI had significantly higher HCV seropositivity rate compared to HBsAg-positive patients. Sequencing of the S gene revealed Y100C, T131N, and D144A mutations. One patient had the M204I and L180M drug-resistance mutations (polymerase). HBV genotypes A (A1, A2), D (D2, D3), and F (F2) were identified. In conclusion, OBI represented almost half of all HBV infections with detectable HBV DNA, suggesting that hepatitis B diagnosis in HIV patients should include in addition to serological markers the detection of HBV DNA.

Full-genome sequences of hepatitis B virus subgenotype D3 isolates from the Brazilian Amazon Region.

The Brazilian Amazon Region is a highly endemic area for hepatitis B virus (HBV). However, little is known regarding the genetic variability of the strains circulating in this geographical region. Here, we describe the first full-length genomes of HBV isolated in the Brazilian Amazon Region; these genomes are also the first complete HBV subgenotype D3 genomes reported for Brazil. The genomes of the five Brazilian isolates were all 3,182 base pairs in length and the isolates were classified as belonging to subgenotype D3, subtypes ayw2 (n = 3) and ayw3 (n = 2). Phylogenetic analysis suggested that the Brazilian sequences are not likely to be closely related to European D3 sequences. Such results will contribute to further epidemiological and evolutionary studies of HBV.

Association of Pre-S/S and Polymerase Mutations with Acute and Chronic Hepatitis B Virus Infections in Patients from Rio de Janeiro, Brazil.

Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.

Hepatitis B and C in Immigrants and Refugees in Central Brazil: Prevalence, Associated Factors, and Immunization.

Introduction: Eliminating hepatitis B and C in immigrant and refugee populations is a significant challenge worldwide. Given the lack of information in Brazil, this study aimed to estimate the prevalence of infections caused by hepatitis B and C viruses and factors associated with hepatitis B in immigrants and refugees residing in central Brazil. Methods: An observational, cross-sectional, and analytical study was conducted from July 2019 to January 2020 with 365 immigrants and refugees. Hepatitis B was detected by a rapid immunochromatographic test, enzyme immunoassay, and chemiluminescence, and hepatitis C by rapid immunochromatographic test. Multiple analysis was used to assess factors associated with hepatitis B infection. Results: Of the participants, 57.8% were from Haiti and 35.6% were from Venezuela. Most had been in Brazil for less than 2 years (71.2%). The prevalence of HBV infection and exposure was 6.6% (95% CI: 4.5-9.6%) and 27.9% (95% CI: 23.6-2.8%), respectively, and 34% had isolated anti-HBs positivity. Reporting a sexually transmitted infection was statistically associated with HBV infection (OR: 7.8; 95% CI: 2.3-26.4). No participant with positive anti-HCV serology was found. Conclusions: The study showed that participants were outside the reach of prevention and control actions for hepatitis B. Therefore, public health strategies must be designed to reach, inform, and vaccinate this group.

Occult infection with HBV intergenotypic A2/G recombinant following acute hepatitis B caused by an HBV/A2 isolate.

Viral and host factors leading to occult hepatitis B virus (HBV) infection (OBI) are not fully understood. Whether HBV genotype may influence the occurrence and course of OBIs is unknown. Here, we describe the case of a patient infected with HBV genotype A2 who developed symptomatic acute hepatitis and did not seroconvert after loss of HBsAg and HBeAg. The acute phase of hepatitis B was followed by a period of more than 2 years during which the DNA of an intergenotypic HBV/A2/G recombinant was intermittently detected in serum.

Full-genome sequences of hepatitis B virus subgenotype D3 isolates from the Brazilian Amazon Region

The Brazilian Amazon Region is a highly endemic area for hepatitis B virus (HBV). However, little is known regarding the genetic variability of the strains circulating in this geographical region. Here, we describe the first full-length genomes of HBV isolated in the Brazilian Amazon Region; these genomes are also the first complete HBV subgenotype D3 genomes reported for Brazil. The genomes of the five Brazilian isolates were all 3,182 base pairs in length and the isolates were classified as belonging to subgenotype D3, subtypes ayw2 (n = 3) and ayw3 (n = 2). Phylogenetic analysis suggested that the Brazilian sequences are not likely to be closely related to European D3 sequences. Such results will contribute to further epidemiological and evolutionary studies of HBV.

Hepatitis B viral markers in banked human milk before and after Holder pasteurization.

BACKGROUND: Blood screening for hepatitis B virus (HBV) is not universally performed for donor selection in human milk banks. OBJECTIVES: To evaluate the frequency of detection of HBV surface antigen (HBsAg) and HBV-DNA in colostrum of HBV-infected nursing mothers before and after Holder pasteurization. STUDY DESIGN: Forty-two concentrated breast milk samples were obtained within two postnatal weeks from 24 HBsAg-positive women (4 HBeAg-positive and 20 HBeAg-negative, anti-HBe-positive) were tested for the presence of HBsAg and HBV-DNA before and after Holder pasteurization (30min at 62.5 degrees C). RESULTS: Before pasteurization, HBsAg and HBV-DNA were found in 14/24 (58%), and 20/24 (75%) first milk samples, respectively, obtained by 4 days after delivery. At least one marker was detected in 20/24 (83%) milk samples. Both markers were identified in milk of HBeAg-positive mothers, and most mothers with anti-HBe in blood had at least one HBV marker. Once detected, viral markers were frequently found in milk samples subsequently obtained from the same woman. Holder pasteurization did not affect the probability of detecting HBsAg (8/18, 44%), HBV-DNA (12/18, 67%), or at least one of them (15/18, 83%). CONCLUSIONS: Although the biological implications of these findings remain to be determined, considering that HBV is highly contagious and most recipients of banked human milk are preterm infants, these findings should be taken into account when donors are enlisted for human milk banks without serological screening.

Estudos de expressão do HBsAg: hepatite B oculta, genótipos do HBV e quimeras de HBV e HCV / Studies of expression of the HBsAg: occult hepatitis B, genotypes of the HBV and chimeras of HBV and HCV

Introdução: O vírus da hepatite B (HBV) é classificado em oito genótipos (A-H), que apresentam uma distribuição geográfica característica nas diferentes regiões do mundo. No Brasil, são encontrados principalmente os genótipos A, D e F. A infecção pelo HBV é comumente diagnosticada pela presença do antígeno de superfície viral (HBsAg) no soro de indivíduos infectados. Mutações no HBsAg podem afetar os níveis de secreção deste antígeno, bem como, alterar a sua conformação, e conseqüentemente, inibir a sua detecção pelos testes imunoenzimáticos. A detecção do DNA viral em pacientes com sorologia negativa para o HBsAg caracteriza a ocorrência de infecção oculta pelo HBV. Partículas híbridas de HBsAg, também denominadas quimeras, têm sido utilizadas com bastante eficiência na apresentação de epítopos exógenos. Objetivos: Realizar estudos de expressão in vitro do HBsAg em células eucarióticas visando (i) associar infecção oculta pelo HBV com mutações de aminoácidos no HBsAg; (ii) avaliar possíveis diferenças na detecção do HBsAg relacionadas aos diferentes genótipos do HBV; e (iii) possibilitar a construção de quimeras de HBV e do vírus da hepatite C (HCV) para produção de proteínas híbridas imunizantes. Metodologia: A clonagem das regiões genômicas do envelope do HBV foi realizada utilizando-se os vetores de expressão em células eucarióticas pcDNA3 e/ou pCI. Para a inserção do segmento de HCV no HBsAg, foi utilizado um sítio de restrição natural localizado na região do epítopo neutralizante do HBsAg. Ensaios de transfecção transitória foram realizados em células CHO e/ou HuH7. O meio de cultura e os extratos celulares foram analisados quanto à detecção de HBsAg por ensaios imunoenzimáticos. Ensaios de imunofluorescência, utilizando um anticorpo monoclonal anti-HBs, foram realizados para detectar a localização intracelular do HBsAg. Resultados: 1) A infecção oculta pelo HBV foi detectada em 6/43 (14por cento) pacientes infectados pelo HIV. A ocorrência de...HBsAg.