JOAO RENATO REBELLO PINHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
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- YY Hepatitis B and C viruses and hepatocellular carcinoma(2022) RAIMONDO, Giovanni; REBELLO-PINHO, Joao R.; PANDURO, Arturo
- Analysis of the complete genome of HBV genotypes F and H found in Brazil and Mexico using the next generation sequencing method(2022) GIONDA, Patricia Oliveira; GOMES-GOUVEA, Michele; MALTA, Fernanda de Mello; SEBE, Pedro; SALLES, Ana Paula Moreira; FRANCISCO, Rodrigo Dos Santos; JOSE-ABREGO, Alexis; ROMAN, Sonia; PANDURO, Arturo; PINHO, Joao Renato RebelloIntroduction and Objectives: Hepatitis B Virus is classified into ten different genotypes (A-J). Genotypes F and H cluster apart from others in phylogenetic trees and is particularly frequent in the Americas. The aim of this study was to sequence complete genomes of samples of HBV genotypes F and H from Brazil and Mexico using next generation sequencing (NGS) and to study relevant characteristics for the disease associated with this virus. Materials and methods: Ninety plasma samples with detectable HBV DNA belonging to the F (n=59) and H (n=31) genotypes were submitted to amplification of the complete HBV genome by three different methologies. Data analysis was developed using bioinformatics tools for quality assurance and comprehensive coverage of the genome. Sequences were aligned with reference sequences for subgenotyping and detecting variants in relevant positions. A phylogenetical tree was constructed using Bayesian methods. Results: HBV genome of 31 samples were amplified and 18 of them were sequenced (HBV/F=16 and HBV/H=2). One genotype F sample was co-infected with the F1b and F3 subgenotypes, while the other samples were all F2a subgenotype. Two genotype H samples clustered with other Mexican sequences. The main variants observed were found in preS and S genes (7/18) and mutations in the precore/core region (11/18). Conclusions: A NGS methodology was applied to F and H genotypes samples from Mexico and Brazil to fully characterize their sequences. This methodology will be relevant for clinical and epidemiological studies of hepatitis B in Latin America (C) 2021 Fundacion Clinica Medica Sur, A.C.
- Unexpected findings of hepatitis B and delta infection in northeastern Brazil: A public health alert(2021) NUNES, Jomar Diogo Costa; SILVA, Diego Luz Felipe da; FONSECA, Lena Maria Barros; FELIPE, Ilana Mirian Almeida; FERREIRA, Beatriz Rossetti; SANTANA, Rodrigo de Carvalho; MARTINELLI, Ana de Lourdes Candolo; SILVA, Antonio Augusto Moura da; PINHO, Joao Renato Rebello; GOUVEA, Michele Soares Gomes; SANTOS, Max Diego Cruz; LIMA, Thais Feres Moreira; ALBUQUERQUE, Ingrid de Campos; SOUZA, Marinilde Teles; MORAES, Maria Joselia Diniz; CALDAS, Arlene de Jesus Mendes; SOUZA, Leticia Alana Barros; SILVA, Camila Maria Pinheiro de Mello e; FERREIRA, Adalgisa de Souza PaivaIntroduction and objectives: Research has shown that hepatitis B (HBV) and Delta virus (HDV) are a worldwide public health problem. This study aims to estimate the prevalence rates of HBV and HDV infection in five municipalities of Maranhao, Northeastern Brazil. Materials and methods: A total sample between 3856 and 4000 individuals. Questionnaires were used to register sociodemographic characteristics and factors associated with transmission. Patients were tested for hepatitis B virus surface antigen (HBsAg), anti-hepatitis B core antigen (anti-HBc), and antibodies against hepatitis Delta virus (anti-HDV). Factors associated with HBV were detected by means of multivariate Poisson regression. Results: Overall, 3983 subjects were included. Ninety-two of the participants were HBsAg-positive (2.30%, 95% CI 1.80-2.80), and anti-HBc was detected in 1535 (38.50%, 95% CI 37-40). The factors associated with the presence of anti-HBc were: (1) Municipality (P < 0.001); Age (P < 0.001); School education (P < 0.001); Illicit drug use (P = 0.001); non-HBV vaccine (P = 0.041). Among the HBsAg carriers, eight were anti-HDVpositive (8.69%, 95% CI 2.90-14.40). The most frequent HBV genotype was D4. The only HDV genotype was HDV-8. Conclusion: HBV exhibited intermediate endemicity in the studied region. Traditional factors were associated with exposure to the virus. The presence of the HDV was confirmed. The most frequent HBV and HDV genotypes were unlike the ones currently described in Brazil. (C) 2020 Fundacion Clinica Medica Sur, A.C.
- Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure(2019) MENDES, Erica Araujo; PILGER, Denise Regina Bairros de; NASTRI, Ana Catharina de Seixas Santos; MALTA, Fernanda de Mello; PASCOALINO, Bruno dos Santos; D'ALBUQUERQUE, Luiz Augusto Carneiro; BALAN, Andrea; JR, Lucio Holanda Gondim de Freitas; DURIGON, Edison Luis; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloIntroduction and objectives: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). Materials and methods: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. Results: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. Conclusions: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment. (C) 2019 Fundacion Clinica Medica Sur, A.C.
- Hepatitis B virus genotypes and subgenotypes and the natural history and epidemiology of hepatitis B(2022) REUTER, Tania Queiroz; GOMES-GOUVEA, Michele; CHUFFI, Samira; DUQUE, Ulisses Horst; CARVALHO, Jose Americo; PERINI, Waltesia; QUEIROZ, Marcello Moro; SEGAL, Ingrid Marques; AZEVEDO, Raymundo Soares; PINHO, Joao Renato RebelloIntroduction and Objectives: Espirito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espirito Santo Hospital. Materials and Methods: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+) and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software. Results: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES. Conclusions: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively. (C) 2021 Fundacion Clinica Medica Sur, A.C.
- High Prevalence of Hepatitis B Subgenotype D4 in Northeast Brazil: an Ancient Relic from African Continent?(2018) CRUZ-SANTOS, Max D.; GOMES-GOUVEA, Michele S.; COSTA-NUNES, Jomar D.; MALTA-ROMANO, Camila; TELES-SOUSA, Marinilde; FONSECA-BARROS, Lena M.; CARRILHO, Flair J.; PAIVA-FERREIRA, Adalgisa de S.; REBELLO-PINHO, Joao R.Introduction. Hepatitis B virus (HBV) infection leads to a chronic liver disease that is distributed worldwide. The characterization of HBV into genotypes/subgenotypes is not only a mere procedure for distinguishing different HBV strains around the world because determining their geographic distribution is crucial to understanding their spread across the world. Material and methods. We characterized different HBV genotypes and subgenotypes in five municipalities located in northeastern Maranhao, in the Brazilian north Atlantic coast. 92 HBsAg-positive individuals were submitted to PCR (polymerase chain reaction). Fifty samples were sequenced using automated Sanger sequencing and classified by phylogenetic methods. Results. Subgenotypes D4 and A1 were found in 42 (84%) and eight (16%) samples, respectively. To our knowledge, this is the first study to describe a high frequency of subgenotype D4 in any population. Subgenotype A1 is frequently found across Brazil, but D4 has been rarely detected and only in a few Brazilian states. This study shows the characterization of HBV subgenotypes from a population based study in the state of Maranhao, particularly in populations that do not have frequent contact with populations from other regions of the world. Conclusion. Our findings showed a HBV subgenotype profile that probably reflect the viruses that were brought with the slave trade from Africa to Maranhao. This study also reinforces the need to evaluate the status of HBV dispersion not only in large urban centers, but also in the hinterland, to enable the implementation of effective control and treatment measures.
- Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population(2019) MAZO, Daniel F.; MALTA, Fernanda M.; STEFANO, Jose Tadeu; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; ALMEIDA, Jazon R.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.Introduction and aim: Studies have shown that two polymorphisms were associated with steatosis and progression of non-alcoholic fatty liver disease (NAFLD) in different populations: the Patatin-like Phospholipase Domain Containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2). However, the frequency and significance of these polymorphisms in an admixed population, i.e., Brazilian, is unknown. Therefore, we aimed to evaluate them in healthy subjects in comparison to patients with NAFLD. Material and methods: This was a multicenter cross-sectional study in 248 patients with biopsy-proven NAFLD and in 134 healthy controls from two tertiary centers in Brazil. PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) polymorphisms were evaluated. Results: In controls, the frequencies of PNPLA3 CC and CG + GG were 49.25% and 50.74%, respectively; in NAFLD patients, this was 31.05% and 68.88% (p = 0.0044, 95% CI 1.037-2.977). PNPLA3 GG subjects had an increased risk (3.29-fold) of having NAFLD when compared to CC subjects (p = 0.0044,95% CI 1.504-7.225). In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4 +/- 25.3 versus 36.7 +/- 40.1 IU/L, p= 0.0395)] and with the presence of liver fibrosis (>= F2 fibrosis, p = 0.0272). TM6SF2 polymorphisms were not in Hardy-Weinberg equilibrium in our NAFLD group precluding further analysis. Conclusion: We demonstrated for the first time that PNPLA3 CG + GG increase the risk of NAFLD among Brazilian subjects. Moreover, PNPLA3 GG was associated with liver enzyme elevation and fibrosis in NASH patients. (C) 2019 Fundacion Clinica Medica Sur, A.C.