FERNANDA DE MELLO MALTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
25 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 25
- 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.
- Prevalence and Pattern of Resistance in NS5A/NS5B in Hepatitis C Chronic Patients Genotype 3 Examined at a Public Health Laboratory in the State of Sao Paulo, Brazil(2021) SANTOS, Ana Paula de Torres; SILVA, Vanessa Cristina Martins; MENDES-CORREA, Maria Cassia; LEMOS, Marcilio Figueiredo; MALTA, Fernanda de Mello; SANTANA, Rubia Anita Ferraz; DASTOLI, Gregorio Tadeu Fernando; CASTRO, Vanessa Fusco Duarte de; PINHO, Joao Renato Rebello; MOREIRA, Regina CeliaPurpose: Globally, it is estimated that 71 million people are chronically infected with hepatitis C, and 10-20% of these will develop cirrhosis and hepatocellular carcinoma. The development of new direct-acting antiviral (DAA) drugs has contributed to sustained virological response (SVR), eliminating the infection and achieving cure of chronic hepatitis C. However, treated patients can develop HCV resistance to DAAs, which can contribute to the failure of treatment. Here, we aimed to evaluate the prevalence and specific pattern of NS5A and NS5B resistance-associated substitutions (RAS) in samples from patients chronically infected with HCV genotype 3a at a public health laboratory, Instituto Adolfo Lutz, Sao Paulo, Brazil. Patients and Methods: Serum samples from the enrolled individuals were submitted to ""in-house"" polymerase chain reaction amplification of NS5A and NS5B non-structural protein genes, which were then sequenced by Sanger method. Results: A total of 170 and 190 samples were amplified and analyzed for NS5A and NS5B, respectively. For NS5A, 20 (12.0%) samples showed some important RAS; 16 (9.0%) showed some type of substitution and 134 (79.0%) showed no polymorphism. No sample showed any RAS for NS5B. Conclusion: This study found important RAS in samples from naive chronic HCV patients in some areas from Sao Paulo. The most prevalent were A62S, A30K, and Y93H, which could indicate an increase in resistance to some DAAs used in HCV treatment.
- 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.
- Molecular diagnosis of strongyloidiasis in tropical areas: a comparison of conventional and real-time polymerase chain reaction with parasitological methods(2015) PAULA, Fabiana Martins de; MALTA, Fernanda de Mello; MARQUES, Priscilla Duarte; SITTA, Renata Barnabe; PINHO, Joao Renato Rebello; GRYSCHEK, Ronaldo Cesar Borges; CHIEFFI, Pedro PauloThis study aimed to evaluate the use of conventional polymerase chain reaction (cPCR) and real-time quantitative PCR (qPCR) in the diagnosis of human strongyloidiasis from stool samples in tropical areas. Stool samples were collected from individuals and were determined to be positive for Strongyloides stercoralis (group I), negative for S. stercoralis (group II) and positive for other enteroparasite species (group III). DNA specific to S. stercoralis was found in 76.7% of group I samples by cPCR and in 90% of group I samples by qPCR. The results show that molecular methods can be used as alternative tools for detecting S. stercoralis in human stool samples in tropical areas.
- Culture isolation and molecular identification of Blastocystis sp. in Brazilian human isolates: preliminary results(2020) MELO, Gessica Baptista de; ROLDAN, William; MALTA, Fernanda de Mello; LESCANO, Susana Angelica Zevallos; CASTILHO, Vera Lucia; GONCALVES, Elenice Messias Do Nascimento; PAULA, Fabiana Martins de; GRYSCHEK, Ronaldo Cesar BorgesBlastocystis sp. is a protist commonly found in stool samples of humans and animals. Biological and genetic factors of this organism remain controversial. The present study aimed to develop and implement the Blastocystis in vitro culture of Brazilian human isolates for routine use. The fecal isolates (n = 20) were maintained in our laboratory by several passages in Pavlova's medium. Cultures were monitored every 72 h by light microscopy. Genomic DNA was extracted to identify the subtypes (STs). In most isolates, the vacuolar form was prevalent. The amoeboid, granular and cystic forms were observed during in vitro cultivation. STs 1, 2, 3. 4 and 7 were identified. Our preliminary results show the generation time and forms present in the in vitro culture of Blastocystis subtypes isolated from Brazilian human isolates. Therefore, we emphasize the use of in vitro culture as a tool in future studies for the better understanding of the biological aspects of Blastocystis sp.
- 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.
- 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 C among blood donors: cascade of care and predictors of loss to follow-up(2017) MACHADO, Soraia Mafra; ALMEIDA-NETO, Cesar de; PINHO, Joao Renato Rebello; MALTA, Fernanda de Mello; CAPUANI, Ligia; CAMPOS, Aleia Faustina; ABREU, Fatima Regina Marques; NASTRI, Ana Catharina de Seixas Santos; SANTANA, Rbia Anita Ferraz; SABINO, Ester Cerdeira; MENDES-CORREA, Maria CassiaOBJECTIVE: To investigate the HCV cascade of care and to identify the factors associated with loss or absence to follow-up of patients identified as infected with hepatitis C through blood donation. METHODS: Blood donors from 1994 to 2012, identified with positive anti-HCV by enzyme immunoassay and immunoblot tests were invited to participate in the study, through letters or phone calls. Patients who agreed to participate were interviewed and their blood samples were collected for further testing. The following variables were investigated: demographic data, data on comorbidities and history concerning monitoring of hepatitis C. Multiple regression analysis by Poisson regression model was used to investigate the factors associated with non-referral for consultation or loss of follow-up. RESULTS: Of the 2,952 HCV-infected blood donors, 22.8% agreed to participate: 394 (58.2%) male, median age 48 years old and 364 (53.8%) Caucasian. Of the 676 participants, 39.7% did not receive proper follow-up or treatment after diagnosis: 45 patients referred not to be aware they were infected, 61 did not seek medical attention and 163 started a follow-up program, but were non-adherent. The main reasons for inadequate follow-up were not understanding the need for medical care (71%) and health care access difficulties (14%). The variables showing a significant association with inadequate follow-up after multiple regression analysis were male gender (PR = 1.40; 95% CI 1.15-1.71), age under or equal to 50 years (PR = 1.36; 95% CI 1.12-1.65) and non-Caucasians (PR = 1.53; 95% CI 1.27-1.84). CONCLUSIONS: About 40.0% of patients did not receive appropriate follow-up. These data reinforce the need to establish strong links between primary care and reference centers and the need to improve access to specialists and treatments.
- Characterization of subtypes of Blastocystis sp. isolated from patients with urticaria, Sao Paulo, Brazil(2019) MELO, Gessica Baptista de; MALTA, Fernanda de Mello; MARUTA, Celina Wakisaka; CRIADO, Paulo Ricardo; CASTILHO, Vera Lucia Pagliusi; GONCALVES, Elenice Messias do Nascimento; ESPIRITO-SANTO, Maria Cristina de Carvalho do; PAULA, Fabiana Martins de; GRYSCHEK, Ronaldo Cesar BorgesBlastocystis sp. is described as an enteric protist prevalent in fecal samples from humans and animals; its pathogenicity and epidemiology are still controversial. Currently, it has been associated with intestinal diseases such as irritable bowel syndrome and clinical manifestations of allergic skin, such as chronic urticaria. In the context of urticaria, it is still uncertain whether this organism is directly related to the allergic manifestation or just a common component of the intestinal microbiota. This study aimed to evaluate the occurrence and molecular diversity of Blastocystis sp. in individuals with urticaria from a dermatology outpatient clinic, Sao Paulo, Brazil. Fecal samples of 58 patients with urticaria were examined using parasitological methods; and subsequently tested by polymerase chain reaction using Blastocystis-specific primers. The subtypes (STs) and alleles (a) were determined using BLASTn and MLST tools. ST1, ST2, ST3, ST4, ST6 and mixed infection (ST1 + ST3) were identified in the patients with urticaria; ST1 (a4), ST3 (a34 and a36) and ST4 (a42) were the most prevalent. Our molecular analyses allowed an initial description of Blastocystis subtypes in patients with urticaria from Sao Paulo city, Brazil. (C) 2019 Published by Elsevier Ltd on behalf of World Federation of Parasitologists.
- 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.
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