FERNANDA DE MELLO MALTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
21 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 21
- Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection(2015) LISBOA-NETO, Gaspar; NOBLE, Caroline F.; PINHO, Joao R. Rebello; MALTA, Fernanda M.; GOMES-GOUVEA, Michele S.; ALVARADO-MORA, Monica V.; SILVA, Mariliza H. da; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; RODRIGUES, Flaviane K.; CARRILHO, Flair J.; MENDES-CORREA, Maria C.Background: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. Methods: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. Results: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. Conclusions: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.
- 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.
- 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.
conferenceObject Serum Lipidomic Profiling for Screening Potential Biomarkers of Liver Cirrhosis among Patients with Chronic Hepatitis C(2015) PASSOS-CASTILHO, Ana Maria; FERRAZ, Maria Lucia; CARVALHO, Valdemir M.; CARDOZO, Karina H.; KIKUCHI, Luciana; CHAGAS, Aline; PINHO, Joao Renato R.; GOMES-GOUVEA, Michele S.; MALTA, Fernanda; CARRILHO, Flair J.; GRANATO, Celso- 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.
- 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.
conferenceObject CHARACTERIZATION OF CLINICAL PREDICTORS OF NATURALLY OCCURRING NS3/NS4A PROTEASE POLYMORPHISM IN GENOTYPE 1 HEPATITIS C VIRUS INFECTED PATIENTS(2015) LISBOA NETO, G.; NOBLE, C.; PINHO, J. R. R.; MALTA, F. M.; GOMES-GOUVEA, M. S.; ALVARADO-MORA, M. V.; SILVA, M. H.; LEITE, A. G.; PICCOLI, L. Z.; CARRILHO, F. J.; MENDES-CORREA, M. C.- The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C(2021) OLIVEIRA, Arthur Ivan N.; MALTA, Fernanda M.; ZITELLI, Patricia Momoyo Y.; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.; MENDES-CORREA, Maria Cassia; PESSOA, Mario G.; MAZO, Daniel F.BackgroundDespite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies.MethodsThis cross-sectional study enrolled 365 treatment-naive patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C>T) and PNPLA3 (rs738409 c.444C>G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome.ResultsIn HCV subjects, the frequencies of TM6SF2 CC and CT+TT were 89% and 11%, while PNPLA3 frequencies of CC and CG+GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT+TT genotype in HCV was associated with significant liver fibrosis (p=0.047; OR 1.953; 95% CI 1.009-3.788). In comparison to the CT+TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p=0.002), higher frequency of arterial hypertension (p=0.032), obesity (p=0.030), metabolic syndrome (p=0.014) and lower total cholesterol levels (p=0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p=0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis.ConclusionIn this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV.
conferenceObject SERUM LIPIDOMIC PROFILING FOR SCREENING POTENTIAL BIOMARKERS OF HEPATOCELLULAR CARCINOMA BY ULTRAPERFORMANCE LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY(2015) PASSOS-CASTILHO, A. M.; CARVALHO, V. M.; CARDOZO, K. H. M.; KIKUCHI, L.; CHAGAS, A.; PINHO, J. R.; GOMES-GOUVEA, M. S.; MALTA, F.; CARRILHO, F. J.; GRANATO, C. F. H.- Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases(2017) CHACHA, Silvana Gama Florencio; GOMES-GOUVEA, Michele Soares; MALTA, Fernanda de Mello; FERREIRA, Sandro da Costa; VILLANOVA, Mrcia Guimaraes; SOUZA, Fernanda Fernandes; TEIXEIRA, Andreza Correa; PASSOS, Afonso Dinis da Costa; PINHO, Joao Renato Rebello; MARTINELLI, Ana de Lourdes CandoloBACKGROUND In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.
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