ANA PAULA MOREIRA SALLES
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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- 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.
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.- 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.
- Pulmonary and systemic involvement in COVID-19 patients assessed with ultrasound-guided minimally invasive autopsy(2020) DUARTE-NETO, Amaro N.; MONTEIRO, Renata A. A.; SILVA, Luiz F. F. da; MALHEIROS, Denise M. A. C.; OLIVEIRA, Ellen P. de; THEODORO-FILHO, Jair; PINHO, Joao R. R.; GOMES-GOUVEA, Michele S.; SALLES, Ana P. M.; OLIVEIRA, Ilka R. S. de; MAUAD, Thais; SALDIVA, Paulo H. N.; DOLHNIKOFF, MarisaAims Brazil ranks high in the number of coronavirus disease 19 (COVID-19) cases and the COVID-19 mortality rate. In this context, autopsies are important to confirm the disease, determine associated conditions, and study the pathophysiology of this novel disease. The aim of this study was to assess the systemic involvement of COVID-19. In order to follow biosafety recommendations, we used ultrasound-guided minimally invasive autopsy (MIA-US), and we present the results of 10 initial autopsies. Methods and results We used MIA-US for tissue sampling of the lungs, liver, heart, kidneys, spleen, brain, skin, skeletal muscle and testis for histology, and reverse transcription polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 RNA. All patients showed exudative/proliferative diffuse alveolar damage. There were intense pleomorphic cytopathic effects on the respiratory epithelium, including airway and alveolar cells. Fibrinous thrombi in alveolar arterioles were present in eight patients, and all patients showed a high density of alveolar megakaryocytes. Small thrombi were less frequently observed in the glomeruli, spleen, heart, dermis, testis, and liver sinusoids. The main systemic findings were associated with comorbidities, age, and sepsis, in addition to possible tissue damage due to the viral infection, such as myositis, dermatitis, myocarditis, and orchitis. Conclusions MIA-US is safe and effective for the study of severe COVID-19. Our findings show that COVID-19 is a systemic disease causing major events in the lungs and with involvement of various organs and tissues. Pulmonary changes result from severe epithelial injury and microthrombotic vascular phenomena. These findings indicate that both epithelial and vascular injury should be addressed in therapeutic approaches.
- NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features(2022) RECUERO, Amanda Medeiros; GOMES, Larissa Garcia; MACIEL, Gustavo Arantes Rosa; MALTA, Fernanda de Mello; SALLES, Ana Paula Moreira; VEZOZZO, Denise Cerqueira Paranagua; BARACAT, Edmund Chada; PINHO, Joao Renato Rebello; CARRILHO, Flair Jose; STEFANO, Jose Tadeu; OLIVEIRA, Claudia P.Background: The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. Methods: This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. Results: The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance >= 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values >= 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. Conclusions: In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.
- 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.
- 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.
- 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 RebelloThe 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.
conferenceObject PNPLA3 but not TM6SF2 polymorphisms were associated with higher degrees of steatosis and liver fibrosis among Brazilian NAFLD patients(2017) MAZO, Daniel F.; MALTA, Fernanda; STEFANO, Jose Tadeu; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; ALMEIDA, Jazon Romilson S.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.- Lipase and factor V (but not viral load) are prognostic factors for the evolution of severe yellow fever cases(2019) CASADIO, Luciana Vilas Boas; SALLES, Ana Paula Moreira; MALTA, Fernanda de Mello; LEITE, Gabriel Fialkovitz; HO, Yeh-Li; GOMES-GOUVEA, Michele Soares; MALBOUISSON, Luiz Marcelo Sa; LEVIN, Anna S.; AZEVEDO NETO, Raymundo Soares de; CARRILHO, Flair Jose; NASTRI, Ana Catharina Seixas Santos; PINHO, Joao Renato RebelloBACKGROUND Despite a highly efficacious vaccine, yellow fever (YF) is still a major threat in developing countries and a cause of outbreaks. In 2018, the Brazilian state of Sao Paulo witnessed a new YF outbreak in areas where the virus has not been detected before. OBJECTIVE The aim is to describe the clinical and laboratorial characteristics of severe cases of YF, evaluate viral to determine markers associated with fatal outcome. METHODS Acute severe YF cases (n = 62) were admitted to the Intensive Care Unit of a reference hospital and submitted to routine laboratorial evaluation on admission. YFV-RNA was detected in serum and urine by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and then sequenced. Patients were classified in two groups: survival or death. FINDINGS In the univariate analysis the following variables were associated with outcome: alanin aminotransferase (ALT), aspartat aminotransferase (AST), AST/ALT ratio, total bilirubin (TB), chronic kidney disease epidemiology collaboration (CKD-EPI), ammonia, lipase, factor V, international normalised ratio (INR), lactate and bicarbonate. Logistic regression model showed two independent variables associated with death: lipase [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.007 to 1.030, p = 0.002], and factor V (OR -0.955, 95% CI 0.929 to 0.982, p = 0.001). The estimated lipase and factor V cut-off values that maximised sensitivity and specificity for death prediction were 147.5 U/L [area under the curve (AUC) = 0.879], and 56.5% (AUC = 0.913). MAIN CONCLUSIONS YF acute severe cases show a generalised involvement of different organs (liver, spleen, heart, kidneys, intestines and pancreas), and different parameters were related to outcome. Factor V and lipase are independent variables associated with death, reinforcing the importance of hemorrhagic events due to fulminant liver failure and pointing to pancreatitis as a relevant event in the outcome of the disease.