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
31 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 31
- Ability of a Combined FIB4/miRNA181a Score to Predict Significant Liver Fibrosis in NAFLD Patients(2021) LIMA, Rodrigo Vieira Costa; STEFANO, Jose Tadeu; MALTA, Fernanda de Mello; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; ARRESE, Marco; OLIVEIRA, Claudia P.Liver biopsy is the gold standard for assessing fibrosis, but there is a need to seek non-invasive biomarkers for this purpose. The aim of this study was to evaluate the correlation between the serum levels of the microRNAs miR-21, miR-29a, miR-122, miR-155 and miR-181a and the phenotypic expression of NAFLD. A cross-sectional study was carried out on 108 NAFLD patients diagnosed by liver biopsy. FIB-4 and NAFLD fibrosis scores were calculated. The comparison between the distributions of microRNA values according to the presence or absence of histological fibrosis (F2-F4) was performed. A multivariate logistic regression analysis was performed to build a score for predicting fibrosis using FIB-4 and Ln (miR-181a) as independent variables. Only miR-181a showed a statistical difference between patients with significant liver fibrosis (>F2) and those without (F0-F1) (p = 0.017). FIB-4 revealed an AUC on the ROC curve of 0.667 to predict clinically significant fibrosis (F2-F4). When assessed using the score in association with Ln (miR-181a), there was an improvement in the ROC curve, with an AUC of 0.71. miR-181a can be used as a non-invasive method of predicting fibrosis in NAFLD, and an association with FIB-4 has the potential to increase the accuracy of each method alone.
- Dynamics of Hepatitis D (delta) virus genotype 3 in the Amazon region of South America(2011) ALVARADO-MORA, Monica Viviana; ROMANO, Camila Malta; GOMES-GOUVEA, Michele Soares; GUTIERREZ, Maria Fernanda; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloHepatitis delta virus (HDV) is widely distributed and associated with fulminant hepatitis epidemics in areas with high prevalence of HBV. Several studies performed in the 1980s showed data on HDV infection in South America, but there are no studies on the viral dynamics of this virus. The aim of this study was to conduct an evolutionary analysis of hepatitis delta genotype 3 (HDV/3) prevalent in South America: estimate its nucleotide substitution rate, determine the time of most recent ancestor (TMRCA) and characterize the epidemic history and evolutionary dynamics. Furthermore, we characterized the presence of HBV/HDV infection in seven samples collected from patients who died due to fulminant hepatitis from Amazon region in Colombia and included them in the evolutionary analysis. This is the first study reporting HBV and HDV sequences from the Amazon region of Colombia. Of the seven Colombian patients, five were positive for HBV-DNA and HDV-RNA. Of them, two samples were successfully sequenced for HBV (subgenotypes F3 and Fib) and the five samples HDV positive were classified as HDV/3. By using all HDV/3 available reference sequences with sampling dates (n = 36), we estimated the HDV/3 substitution rate in 1.07 x 10(-3) substitutions per site per year (s/s/y), which resulted in a time to the most recent common ancestor (TMRCA) of 85 years. Also, it was determined that HDV/3 spread exponentially from early 1950s to the 1970s in South America. This work discusses for the first time the viral dynamics for the HDV/3 circulating in South America. We suggest that the measures implemented to control HBV transmission resulted in the control of HDV/3 spreading in South America, especially after the important raise in this infection associated with a huge mortality during the 1950s up to the 1970s. The differences found among HDV/3 and the other HDV genotypes concerning its diversity raises the hypothesis of a different origin and/or a different transmission route.
- Hepatitis B (HBV), Hepatitis C (HCV) and Hepatitis Delta (HDV) Viruses in the Colombian Population-How Is the Epidemiological Situation?(2011) ALVARADO-MORA, Monica Viviana; FERNANDEZ, Maria Fernanda Gutierrez; GOMES-GOUVEA, Michele Soares; AZEVEDO NETO, Raymundo Soares de; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloBackground: Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. Methodology/Principal Findings: This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Choco, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (p < 0.001) were more frequent in Amazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Choco (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andres (15.33%) p < 0.001. Prevalence of anti-HBc increased with age; HBsAg varied from 1.97 to 8.39% (p = 0.033). Amazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andres Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. Conclusions/Significance: In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results.
- TWO SEQUENTIAL PCR AMPLIFICATIONS FOR DETECTION OF Schistosoma mansoni IN STOOL SAMPLES WITH LOW PARASITE LOAD(2012) ESPIRITO-SANTO, Maria Cristina Carvalho do; ALVARADO-MORA, Monica Viviana; PINTO, Pedro Luiz Silva; CARRILHO, Flair Jose; PINHO, Joao Renato Rebello; GRYSCHEK, Ronaldo Cesar BorgesSchistosomiasis constitutes a major public health problem, with an estimated 200 million individuals infected worldwide and 700 million people living in risk areas. In Brazil there are areas of high, medium and low endemicity. Studies have shown that in endemic areas with a low prevalence of Schistosoma infection the sensitivity of parasitological methods is clearly reduced. Consequently diagnosis is often impeded due to the presence of false-negative results. The aim of this study is to present the PCR reamplification (Re-PCR) protocol for the detection of Schistosoma mansoni in samples with low parasite load (with less than 100 eggs per gram (epg) of feces). Three methods were used for the lysis of the envelopes of the S. mansoni eggs and two techniques of DNA extraction were carried out. Extracted DNA was quantified, and the results suggested that the extraction technique, which mixed glass beads with a guanidine isothiocyanate/phenol/chloroform (GT) solution, produced good results. PCR reamplification was conducted and detection sensitivity was found to be five eggs per 500 mg of artificially marked feces. The results achieved using these methods suggest that they are potentially viable for the detection of Schistosoma infection with low parasite load.
- Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography-mass spectrometry(2015) PASSOS-CASTILHO, Ana Maria; CARVALHO, Valdemir Melechco; CARDOZO, Karina Helena Morais; KIKUCHI, Luciana; CHAGAS, Aline Lopes; GOMES-GOUVEA, Michele Soares; MALTA, Fernanda; NASTRI, Ana Catharina de Seixas-Santos; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; GRANATO, Celso Francisco HernandesBackground: Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers. Methods: An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases. Results: The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols. Conclusions: UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.
- HCV inter-subtype 1a/1b recombinant detected by complete-genome next-generation sequencing(2016) GASPARETO, Karine Vieira; RIBEIRO, Roberto Marques; MALTA, Fernanda de Mello; GOMES-GOUVEA, Michele Soares; MUTO, Nair Hideko; MENDES-CORREA, Maria Cassia; ROZANSKI, Andrei; CARRILHO, Flair Jose; SABINO, Ester Cerdeira; PINHO, Joao Renato RebelloNext-generation sequencing (NGS) provides a practical approach to HCV complete-genome sequencing, detecting low-frequency variants and allowing analysis of viral genetic diversity (quasispecies) in the sample, and so far, it is very useful for identifying preexisting drug-resistant mutants and emerging escape mutations, as well as detecting viral recombinants containing genomic regions from different genotypes and subtypes. The aim of this study was to analyze the complete coding region of hepatitis C virus (HCV) genotype 1 (subtypes 1a and 1b) from patients with chronic infection who were direct-acting antiviral (DAA) na < ve. Next-generation sequencing (Ion Torrent (TM) PGM) was used to determine the sequence of the complete coding region of 100 HCV-monoinfected DAA-na < ve patients (51 and 49 subtypes 1a and 1b, respectively). We report the first description of nearly complete HCV genome sequences of subtype 1a and 1b isolates from a large population of Brazilian patients with chronic hepatitis C, and HCV-1a grouped in two different clades. Using this methodology, an inter-subtype 1a/1b recombinant was identified in this study.
- Mutation in the S Gene a Determinant of the Hepatitis B Virus Associated With Concomitant HBsAg and Anti-HBs in a Population in Northeastern Brazil(2017) ALBUQUERQUE, Ingrid de Campos; SOUSA, Marinilde Teles; SANTOS, Max Diego Cruz; NUNES, Jomar Diogo Costa; MORAES, Maria Joselia Diniz; GOMES-GOUVEA, Michele Soares; PINHO, Joao Renato Rebelo; CARRILHO, Flair Jose; FONSECA, Lena Maria Barros; FERREIRA, Adalgisa de Sousa PaivaMutations in the a determinant of S gene may develop co-existence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in the serum of infected hepatitis B virus (HBV) individuals. Mutations in this region may change the antigenicity of HBsAg, which in turn, lead to escape of neutralizing action of anti-HBs antibodies. This study identified individuals with concomitant HBsAg and anti-HBs serological markers in individuals of Maranhao, Northeastern Brazil. Samples from a population-based study were evaluated for HBsAg, anti-HBs, and anti-HBc, and those that tested positive for simultaneous HBsAg and anti-HBs were submitted to HBV DNA quantification and S gene characterization by Sanger sequencing. Mutations were investigated in the a determinant located in major hydrophilic region (MHR) of the S gene. Among 3,984 samples analyzed, 92 (2.3%) were positive for HBsAg and three had the atypical HBsAg and anti-HBs-positive profile (3.26%). The frequency of HBsAg and anti-HBs co-existence was similar to previous studies. Only one individual harbored mutation in the S gene a determinant associated with this profile. Little is known about this phenomenon; however, studies as ours may contribute for future enlightenment of this important issue. (C) 2016 Wiley Periodicals, Inc.
- 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.
conferenceObject NON-Invasive Biomarkers to Monitoring LIVER Disease Progression in Nash Patients(2018) MALTA, Fernanda; LIMA, Rodrigo V.; SALLES, Ana Paula M.; STEFANO, Jose Tadeu; MAZO, Daniel; ALVES, Venancio A. F.; CARRILHO, Flair Jose; PINHO, Joao Renato R.; OLIVEIRA, Claudia P. M. S.- Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer(2016) MOREIRA, Joao Paulo; MALTA, Fernanda de Mello; DINIZ, Marcio Augusto; KIKUCHI, Luciana; CHAGAS, Aline Lopes; LIMA, Livia de Souza Botelho; GOMES-GOUVEA, Michele Soares; CASTRO, Vanessa Fusco Duarte de; SANTANA, Rubia Anita Ferraz; SUMITA, Nairo Massakazu; VEZOZZO, Denise Cerqueira Paranagua; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloBackground: Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. Method of study: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). Results: the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). Conclusions: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.