ANA CATHARINA DE SEIXAS SANTOS NASTRI

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: FLAIR JOSE CARRILHO ×

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  • article 19 Citação(ões) na Scopus
    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 Hernandes
    Background: 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.
  • article 4 Citação(ões) na Scopus
    The Molecular Characterization of Hepatitis A Virus Strains Circulating during Hepatitis A Outbreaks in Sao Paulo, Brazil, from September 2017 to May 2019
    (2022) CHUFFI, Samira; GOMES-GOUVEA, Michele S.; CASADIO, Luciana V. B.; NASTRI, Ana Catharina S. S.; GONZALEZ, Mario P.; COTIA, Andre L. F.; ARANDA, Amanda G. D.; TENORE, Simone B.; ONO, Suzane K.; MALTA, Fernanda M.; MADALOSSO, Geraldine; FERREIRA, Paulo R. A.; CARRILHO, Flair J.; PINHO, Joao R. R.
    Outbreaks of hepatitis A may occur in countries of medium and high socioeconomic levels in which the population generally exhibits an increased susceptibility in young adults to this infection if they are not vaccinated against the hepatitis A virus (HAV). In Europe, an outbreak involved approximately 22 European countries with 4475 cases reported from 2016 to 2018; most of them were men who have sex with men (MSM). This outbreak expanded to North and South America, including Brazil, particularly in Sao Paulo city with 1547 reported cases from 2016 to 2019. In the present study, we characterized the HAV strains involved in the acute hepatitis A cases identified in the reference centers of Sao Paulo city during this outbreak. A total of 51 cases with positive anti-HAV IgM were included, 80.4% male, 68.6% of them between 20 and 40 years old and 41.7% MSM. HAV RNA was detected in 92% (47/51) of the cases. Subgenotype IA of HAV was identified and most of the strains were closely related to that isolated in outbreaks that occurred in different European countries in 2016. These results showed the epidemiological relation between these outbreaks and reinforce the need to implement vaccination against hepatitis A for the adult population, particularly for a population with a high-risk behavior.
  • article 28 Citação(ões) na Scopus
    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 Rebello
    Introduction 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.
  • article 9 Citação(ões) na Scopus
    Association of IFNL3 and IFNL4 polymorphisms with hepatitis C virus infection in a population from southeastern Brazil
    (2016) NASTRI, Ana Catharina de Seixas Santos; MALTA, Fernanda de Mello; DINIZ, Marcio Augusto; YOSHINO, Alessandra; ABE-SANDES, Kiyoko; SANTOS, Sidney Emanuel Batista dos; LYRA, Andre de Castro; CARRILHO, Flair Jose; PINHO, Joao Renato Rebello
    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and associated complications such as liver cirrhosis and hepatocellular carcinoma (HCC). Viral and host factors are known to be predictors for antiviral therapy. Host factors that are predictors of sustained viral response (SVR) were discovered by genome-wide association studies (GWAS), including single-nucleotide polymorphisms (SNPs) in or near the interferon lambda gene (rs8099917, rs12979860 and rs368234815). The aim of the present study was to verify the genotype frequencies of SNPs rs8099917, rs12979860 and rs368234815 and to evaluate the association between SNPs and the outcome of HCV infection, taking into account the population ancestry. In this study, there was an association of the three polymorphisms with both clinical outcome and response to treatment with PEG-IFN and RBV. The polymorphisms rs12979860 and rs368234815 were associated with increased sensitivity (97.7 %, 95 % CI 87.2-100, and 93.3 %, 95 % CI 81.3-98.3; respectively) and with a greater predictive value of a positive response to treatment. In multivariable analysis adjusted by gender, age and ancestry, the haplotype G/T/Delta G was related to non-response to treatment (OR = 21.09, 95 % CI 5.33-83.51; p < 0.001) and to a higher chance of developing chronic infection (OR = 5.46, 95 % CI 2.06-14.46; p = 0.001) when compared to the haplotype T/C/TT. These findings may help to adjust our treatment policies for HCV infection based on greater certainty in studies with populations with such genetic characteristics, as well as allowing us to get to know the genetic profile of our population for these polymorphisms.
  • conferenceObject
    COMBINATION OF IFNL4 AND IFNL3 HAPLOTYPES IMPROVES PREDICTION OF RESPONSE TO INTERFERON THERAPIES IN PATIENTS FROM AN ADMIXED POPULATION
    (2014) NASTRI, A. C.; MALTA, F.; FARIA, P. L.; OLIVEIRA, K.; CARRILHO, F.; PINHO, J. R.
  • article 6 Citação(ões) na Scopus
    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.
  • article 16 Citação(ões) na Scopus
    Increased hepatic expression of miRNA-122 in patients infected with HCV genotype 3
    (2016) OLIVEIRA, Ketti G.; MALTA, Fernanda M.; NASTRI, Ana C. S. S.; WIDMAN, Azzo; FARIA, Paola L.; SANTANA, Rubia A. F.; ALVES, Venancio A. F.; CARRILHO, Flair J.; PINHO, Joao R. R.
    Hepatitis C virus (HCV) infection affects approximately 3 % of the world population. HCV targets hepatic tissue, and most infected patients develop a chronic infection. Currently, studies have demonstrated an association between HCV-RNA replication and miR-122, the most abundant microRNA in the liver. Our aim was to evaluate liver and serum expression of miR-122 in patients infected with HCV genotypes 1 and 3, and to identify possible associations between miR-122 expression and lipid profiles, HCV viral load, apolipoproteins and liver enzymes. MicroRNAs were isolated from blood and liver tissue, and miR-122 expression was quantified by real-time PCR. HCV viral load was quantified by real-time PCR and HCV genotype, and serum biomarkers were obtained from medical report. The levels of miR-122 were higher in liver than those in blood from individuals infected with HCV genotypes 1 and 3 (p < 0.0001). The tissue levels of miR-122 were higher in subjects infected with HCV genotype 3 (6.22-fold, p < 0.001). A positive correlation was observed between the blood and hepatic levels of miR-122 in patients infected with HCV genotype 1 (r = 0.302, p = 0.026); in these patients, an inverse correlation was observed between serum apolipoprotein A-II (ApoA-II) levels and the blood (r = -0.330; p = 0.014) and hepatic (r = -0.311; p = 0.020) levels of miR-122. In patients infected with HCV genotype 3, there was a positive correlation between the hepatic miR-122 and the high-density lipoprotein-HDL (r = 0.412, p = 0.036) and insulin (r = 0.478, p = 0.044). Lipid metabolism proteins and miR-122 expression levels have different relations in HCV-3- and HCV-1-infected patients.
  • article 40 Citação(ões) na Scopus
    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.
  • article 8 Citação(ões) na Scopus
    Efficacy of sofosbuvir as treatment for yellow fever: protocol for a randomised controlled trial in Brazil (SOFFA study)
    (2019) FIGUEIREDO-MELLO, Claudia; CASADIO, Luciana Vilas Boas; AVELINO-SILVA, Vivian Lida; Ho Yeh-Li; SZTAJNBOK, Jaques; JOELSONS, Daniel; ANTONIO, Marilia Bordignon; PINHO, Joao Renato Rebello; MALTA, Fernanda de Mello; GOMES-GOUVEA, Michele Soares; SALLES, Ana Paula Moreira; CORA, Aline Pivetta; MOREIRA, Carlos Henrique Valente; RIBEIRO, Ana Freitas; NASTRI, Ana Catharina de Seixas Santos; MALAQUE, Ceila Maria Sant'Ana; TEIXEIRA, Ralcyon Francis Azevedo; BORGES, Luciana Marques Sansao; GONZALEZ, Mario Peribanez; PEREIRA JUNIOR, Luiz Carlos; SOUZA, Tamara Newman Lobato; SONG, Alice Tung Wan; D'ALBUQUERQUE, Luiz Augusto Carneiro; ABDALA, Edson; ANDRAUS, Wellington; MARTINO, Rodrigo Bronze de; DUCATTI, Liliana; ANDRADE, Guilherme Marques; MALBOUISSON, Luiz Marcelo Se; SOUZA, Izabel Marcilio de; CARRILHO, Flair Jose; SABINO, Ester Cerdeira; LEVIN, Anna S.
    Introduction An ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YE This is a multicentre open-label randomised controlled trial with 1:1 individual allocation, stratified by severity and by recruiting centre. Methods and analysis Adults with suspected or confirmed YF infection and symptoms lasting up to 15 days are screened. Eligible and consenting patients are randomised to receive oral sofosbuvir 400 mg daily for 10 days or to receive standard clinical care. Viral kinetics are measured daily and the reduction in YF plasma viral load from the sample at inclusion to 72 hours after randomisation will be compared between active and control groups. Clinical outcomes include severity meeting criteria for intensive care support, liver transplantation, in-hospital mortality and mortality within 60 days.
  • article 1 Citação(ões) na Scopus
    Updating the Phylodynamics of Yellow Fever Virus 2016-2019 Brazilian Outbreak With New 2018 and 2019 Sao Paulo Genomes
    (2022) SALLES, Ana Paula Moreira; NASTRI, Ana Catharina de Seixas Santos; HO, Yeh-Li; CASADIO, Luciana Vilas Boas; AMGARTEN, Deyvid Emanuel; AREVALO, Santiago Justo; GOMES-GOUVEA, Michele Soares; CARRILHO, Flair Jose; MALTA, Fernanda de Mello; PINHO, Joao Renato Rebello
    The recent outbreak of yellow fever (YF) in Sao Paulo during 2016-2019 has been one of the most severe in the last decades, spreading to areas with low vaccine coverage. The aim of this study was to assess the genetic diversity of the yellow fever virus (YFV) from Sao Paulo 2016-2019 outbreak, integrating the available genomic data with new genomes from patients from the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP). Using phylodynamics, we proposed the existence of new IE subclades, described their sequence signatures, and determined their locations and time of origin. Plasma or urine samples from acute severe YF cases (n = 56) with polymerase chain reaction (PCR) positive to YFV were submitted to viral genome amplification using 12 sets of primers. Thirty-nine amplified genomes were subsequently sequenced using next-generation sequencing (NGS). These 39 sequences, together with all the complete genomes publicly available, were aligned and used to determine nucleotide/amino acids substitutions and perform phylogenetic and phylodynamic analysis. All YFV genomes generated in this study belonged to the genotype South American I subgroup E. Twenty-one non-synonymous substitutions were identified among the new generated genomes. We analyzed two major clades of the genotypes IE, IE1, and IE2 and proposed the existence of subclades based on their sequence signatures. Also, we described the location and time of origin of these subclades. Overall, our findings provide an overview of YFV genomic characterization and phylodynamics of the 2016-2019 outbreak contributing to future virological and epidemiological studies.