FERNANDA DE MELLO MALTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject HEPATITIS C TREATMENT AMONG HCV-HIV CO-INFECTED PATIENTS IN BRAZIL: A MULTICENTER STUDY ON BASELINE RESISTANCE ANALYSES AND SUSTAINED VIROLOGIC RESPONSE RATE(2019) CORREA, Maria Cassia Mendes; MACHADO, Soraia Mafra; LEITE, Andrea Gurgel Batista; VIGANI, Aline; DIAZ, Ana Claudia Marques Barbosa; FERREIRA, Paulo; CARNAUBA JUNIOR, Dimas; TENORE, Simone; SR., Carlos Eduardo Brandao-Mello; GONZALEZ, Mario; SIROMA, Fabiana; PRADO, Kleber D.; GONGORA, Delzi Vigna Nunes; NETO, Gaspar Lisboa; PINHO, Joao Renato R.; MALTA, Fernanda- 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.
- 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.
- 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.
conferenceObject PREVALENCE AND INFLUENCE OF ""PATATIN-LIKE PHOSPHOLIPASE DOMAIN CONTAINING 3"" (PNPLA3) GENE POLYMORPHISM ON SUSCEPTIBILITY TO NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME(2019) RECUERO, Amanda Medeiros; MALTA, Fernanda; STEFANO, Jose Tadeu; VEZOZZO, Denise Paranagua; GOMES, Larissa Garcia; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund; CASSENOTE, Alex Jones Flores; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P. M. S.- 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.
- Liver Transplantation for Fulminant Hepatitis Attributed to Yellow Fever(2019) SONG, Alice Tung Wan; ABDALA, Edson; MARTINO, Rodrigo Bronze de; MALBOUISSON, Luis Marcelo Sa; TANIGAWA, Ryan Yukimatsu; ANDRADE, Guilherme Marques; DUCATTI, Liliana; DOI, Andre Mario; PINHO, Joao Renato Rebello; GOMES-GOUVEA, Michele Soares; MALTA, Fernanda de Mello; ARANTES JR., Rubens Macedo; TONACIO, Adriana Coracini; PINTO, Lecio Figueira; HADDAD, Luciana Bertocco Paiva; SANTOS, Vinicius Rocha; PINHEIRO, Rafael Soares Nunes; NACIF, Lucas Souto; GALVAO, Flavio Henrique Ferreira; ALVES, Venancio Avancini Ferreira; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz Augusto Carneiro
- 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.