CLAUDIA PINTO MARQUES SOUZA DE OLIVEIRA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Gastroenterologia, Faculdade de Medicina - Docente
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
16 resultados
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- Metabolic signatures across the full spectrum of non-alcoholic fatty liver disease(2022) MCGLINCHEY, Aidan J.; GOVAERE, Olivier; GENG, Dawei; RATZIU, Vlad; ALLISON, Michael; BOUSIER, Jerome; PETTA, Salvatore; OLIVIERA, Claudia de; BUGIANESI, Elisabetta; SCHATTENBERG, Jorn M.; DALY, Ann K.; HYOTYLAINEN, Tuulia; ANSTEE, Quentin M.; ORESIC, MatejBackground & Aims: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease with potentially severe complications including cirrhosis and hepatocellular carcinoma. Previously, we have identified circulating lipid signatures associating with liver fat content and non-alcoholic steatohepatitis (NASH). Here, we develop a metabolomic map across the NAFLD spectrum, defining interconnected metabolic signatures of steatosis (non-alcoholic fatty liver, NASH, and fibrosis). Methods: We performed mass spectrometry analysis of molecular lipids and polar metabolites in serum samples from the European NAFLD Registry patients (n = 627), representing the full spectrum of NAFLD. Using various univariate, multivariate, and machine learning statistical approaches, we interrogated metabolites across 3 clinical perspectives: steatosis, NASH, and fibrosis. Results: Following generation of the NAFLD metabolic network, we identify 15 metabolites unique to steatosis, 18 to NASH, and 15 to fibrosis, with 27 common to all. We identified that progression from F2 to F3 fibrosis coincides with a key pathophysiological transition point in disease natural history, with n = 73 metabolites altered. Conclusions: Analysis of circulating metabolites provides important insights into the metabolic changes during NAFLD progression, revealing metabolic signatures across the NAFLD spectrum and features that are specific to NAFL, NASH, and fibrosis. The F2-F3 transition marks a critical metabolic transition point in NAFLD pathogenesis, with the data pointing to the pathophysiological importance of metabolic stress and specifically oxidative stress. Clinical Trials registration: The study is registered at Clinicaltrials.gov (NCT04442334). Lay summary: Non-alcoholic fatty liver disease is characterised by the build-up of fat in the liver, which progresses to liver dysfunction, scarring, and irreversible liver failure, and is markedly increasing in its prevalence worldwide. Here, we measured lipids and other small molecules (metabolites) in the blood with the aim of providing a comprehensive molecular overview of fat build-up, liver fibrosis, and diagnosed severity. We identify a key metabolic 'watershed' in the progression of liver damage, separating severe disease from mild, and show that specific lipid and metabolite profiles can help distinguish and/or define these cases. (c) 2022 The Author(s).
conferenceObject YSTRATEGIES TO ELIMINATE HEPATITIS C VIRUS INFECTION IN THE AMERICAS(2023) DIAZ, Luis Antonio; GARCIA, Sergio; AYARES, Gustavo; URIBE, Javier; IDALSOAGA, Francisco; FUENTEALBA, Jose Miguel; FUENTES-LOPEZ, Eduardo; MEDEL, Maria Paz; RAMIREZ-CADIZ, Carolina A.; KHAN, Rayan; LAZO, Mariana; FERRECCIO, Catterina; MENDIZABAL, Manuel; DIRCHWOLF, Melisa Melisa; SALAZAR, Patricia Guerra; OLIVEIRA, Claudia P. M. S.; PESSOA, Mario G.; ALVARES-DA-SILVA, Mario R.; SEBASTIANI, Giada; BRAHMANIA, Mayur; RAMJI, Alnoor; NIAZI, Mina; KO, Hin Hin; FELD, Jordan J.; RESTREPO, Juan Carlos; QUESADA, Wagner Enrique Ramirez; ALFARO, Omar; FERNANDEZ, Marlen Ivon Castellanos; ESTUPINAN, Enrique Carrera; AGUIRRE, Jose Roberto; MALDONADO, Katherine; SANCHEZ, Abel; SANCHEZ, Marco; SR., Teresa Andara; CASTRO-NARRO, Graciela Elia; CHAVEZ-TAPIA, Norberto Carlos; MENDEZ-SANCHEZ, Nahum; ADAMES-ALMENGOR, Enrique; LOMBARDO, Julissa; SR., Marcos Girala; MORAN, Elias; PADILLA-MACHACA, Martin; FERRER, Javier Diaz; TAGLE, Martin; MAINARDI, Vitoria; HERNANDEZ, Nelia; MARTINEZ, Edmundo; ALVARADO-TAPIAS, Edilmar; LEON, Roberto; TALAL, Andrew; THOMAS, Emmanuel; SPRINGER, Sandra; SICILIA, Mauricio Garcia Saenz de; ZHANG, Wei; BAJAJ, Jasmohan S.; TAPPER, Elliot B.; IZZY, Manhal; GISH, Robert G.; ATTAR, Bashar M.; COTTER, Thomas G.; LUCEY, Michael R.; KAMATH, Patrick S.; SINGAL, Ashwani K.; BATALLER, Ramon; MEZZANO, Gabriel; SOZA, Alejandro; LAZARUS, Jeffrey V.; ARRESE, Marco; ARAB, Juan Pablo- Association of UCP3 Polymorphisms with Nonalcoholic Steatohepatitis and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease Brazilian Patients(2022) TODA-OTI, Karla Sawada; STEFANO, Jose Tadeu; CAVALEIRO, Ana Mercedes; CARRILHO, Flair Jose; CORREA-GIANELLA, Maria Lucia; OLIVEIRA, Claudia Pinto Marques de Souza deBackground: We investigated the possible association of uncoupling protein 3 gene (UCP3) single nucleotide polymorphisms (SNPs) with nonalcoholic steatohepatitis (NASH) and metabolic syndrome (MetS) in nonalcoholic fatty liver disease (NAFLD) Brazilian patients.Methods: UCP3 SNPs rs1726745, rs3781907, and rs11235972 were genotyped in 158 biopsy-proven NAFLD Brazilian patients. Statistics was performed with JMP, R, and SHEsis softwares.Results: The TT genotype of rs1726745 was associated with less occurrence of MetS (P = 0.006) and with lower body mass index (BMI) in the entire NAFLD sample (P = 0.01) and in the NASH group (P = 0.02). The rs1726745-T was associated with lower values of AST (P = 0.001), ALT (P = 0.0002), triglycerides (P = 0.01), and total cholesterol (P = 0.02) in the entire NAFLD sample. Between groups, there were lower values of aminotransferases strictly in individuals with NASH (AST, P = 0.002; ALT, P = 0.0007) and with MetS (AST, P = 0.002; ALT, P = 0.001). The rs3781907-G was associated with lower GGT elevation values in the entire NAFLD sample (P = 0.002), in the NASH group (P = 0.004), and with MetS group (P = 0.003) and with protection for advanced fibrosis (P = 0.01). The rs11235972-A was associated with lower GGT values in the entire NAFLD sample (P = 0.006) and in the NASH group (P = 0.01) and with MetS group (P = 0.005), with fibrosis absence (P = 0.01) and protection for advanced fibrosis (P = 0.01). The TAA haplotype was protective for NASH (P = 0.002), and TGG haplotype was protective for MetS (P = 0.01).Conclusion: UCP3 gene variants were associated with protection against NASH and MetS, in addition to lower values of liver enzymes, lipid profile, BMI and, lesser fibrosis severity in the studied population.
- Non-pharmacological management options for MAFLD: a practical guide(2023) STEFANO, Jose Tadeu; DUARTE, Sebastiao Mauro Bezerra; ALTIKES, Renato Gama Ribeiro Leite; OLIVEIRA, Claudia P. P.Lifestyle changes should be the main basis for any treatment for metabolic dysfunction-associated fatty liver disease (MAFLD), aiming to increase energy expenditure, reduce energy intake and improve the quality of nutrients consumed. As it is a multifactorial disease, approaches such as physical exercise, a better dietary pattern, and possible pharmacological intervention are shown to be more efficient when used simultaneously to the detriment of their applications. The main treatment for MAFLD is a lifestyle change consisting of diet, activity, exercise, and weight loss. The variables for training prescription such as type of physical exercise (aerobic or strength training), the weekly frequency, and the intensity most indicated for the treatment of MAFLD remain uncertain, that is, the recommendations must be adapted to the clinical conditions comorbidities, and preferences of each subject in a way individual. This review addresses recent management options for MAFLD including diet, nutrients, gut microbiota, and physical exercise.
- Impaired anti-HBV vaccine response in non-cirrhotic chronic HCV is not overcome by double dose regimen: randomized control trial(2023) MEDEIROS, Roseane P.; TERRAULT, Norah A.; MAZO, Daniel F.; OLIVEIRA, Claudia P.; DODGE, Jennifer; ZITELLI, Patricia M.; LOPES, Marta H.; CARRILHO, Flair J.; PESSOA, Mario G.Introduction and Objectives: Some studies suggest chronic HCV infection diminishes responses to the antiHBV vaccine. We evaluated the efficacy of double versus standard dose HBV vaccination among HCV patients without cirrhosis.Patients and Methods: 141 adults with untreated chronic HCV were randomized to HBV vaccination with double dose (40 mu g) or standard dose (20 mu g) at 0,1 and 6 months; 70 healthy HCV-negative patients given standard dose served as controls. Vaccine response was defined by anti-HBs >= 10 mIU/mL.Results: 128 patients (60 double, 68 standard doses) completed the study. Patients were of median age 52 years, 61% female, 60% fibrosis <2 of 4, and 76% genotype 1 with median 6-log 10 IU/mL HCV RNA. Overall seroprotection rate was 76.7% (95% CI: 65-87) in the 40 mu g versus 73.5% (95% CI: 63-84) in the 20 mu g dose HCV-positive groups (p =0.68) and 91.2% (95%CI:84-99) in HCV-negative controls (p =0.011 and 0.003, respectively). In multivariate logistic regression, vaccine dose (double vs. standard dose) was not associated with vaccine response (OR=0.63, p =0.33). Of 32 HCV-infected patients who were non-responders to 3- doses, 25 received the fourth dose of vaccine. The fourth dose seroconversion rate for the 40 mu g and 20 mu g groups were 45.5% and 21.4%, respectively.Conclusions: In HCV-infected patients without cirrhosis, impaired responses to HBV vaccination cannot be overcome by the use of double dose HBV vaccination, but adding a fourth dose of vaccine for non-responders may be an effective strategy. Other adjuvant measures are needed to enhance seroconversion rates in these patients. Trial register: U 1111-1264-2343 (www.ensaiosclinicos.gov.br)(c) 2022 Fundacion Clinica Medica Sur, A.C.
conferenceObject BRAZILIAN PATIENTS WITH CIRRHOSIS HAVE LOWER HOSPITALIZATIONS AND HIGHER MICROBIAL DIVERSITY RELATED TO HEALTHIER DIET COMPARED TO AMERICAN PATIENTS(2021) ALVARES-DA-SILVA, Mario R.; OLIVEIRA, Claudia P.; FAGAN, Andrew; LONGO, Larisse; THOEN, Rutiane U.; YOSHIMURA, Patricia M.; FERREIRA, Zitelli Renee M. Tanaka; MCGEORGE, Sara; FARIAS, Alberto Q.; SIKAROODI, Masoumeh; GILLEVET, Patrick M.; BAJAJ, Jasmohan S.- Rifaximin on epigenetics and autophagy in animal model of hepatocellular carcinoma secondary to metabolic-dysfunction associated steatotic liver disease(2024) MICHALCZUK, Matheus Truccolo; LONGO, Larisse; KEINGESKI, Melina Belen; BASSO, Bruno de Souza; GUERREIRO, Gabriel Tayguara Silveira; FERRARI, Jessica T.; VARGAS, Jose Eduardo; OLIVEIRA, Claudia P.; URIBE-CRUZ, Carolina; CERSKI, Carlos Thadeu Schmidt; FILIPPI-CHIELA, Eduardo; ALVARES-DA-SILVA, Mario ReisBACKGROUND Prevalence of hepatocellular carcinoma (HCC) is increasing, especially in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). AIM To investigate rifaximin (RIF) effects on epigenetic/autophagy markers in animals. METHODS Adult Sprague-Dawley rats were randomly assigned (n = 8, each) and treated from 5-16 wk: Control [standard diet, water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD), diethylnitrosamine (DEN) in drinking water and Veh gavage], and RIF [HFCD, DEN and RIF (50 mg/kg/d) gavage]. Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained. RESULTS All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis, and cirrhosis, but three RIF-group did not develop HCC. Comparing animals who developed HCC with those who did not, miR-122, miR-34a, tubulin alpha-1c (Tuba-1c), metalloproteinases-2 (Mmp2), and metalloproteinases-9 (Mmp9) were significantly higher in the HCC-group. The opposite occurred with Becn1, coactivator associated arginine methyltransferase-1 (Carm1), enhancer of zeste homolog-2 (Ezh2), autophagy-related factor LC3A/B (Map1 Lc3b), and p62/sequestosome-1 (p62/SQSTM1)-protein. Comparing with controls, Map1 Lc3b, Becn1 and Ezh2 were lower in HCC and RIF-groups (P < 0.05). Carm1 was lower in HCC compared to RIF (P < 0.05). Hepatic expression of Mmp9 was higher in HCC in relation to the control; the opposite was observed for p62/Sqstm1 (P < 0.05). Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control (P = 0.024). There was no difference among groups for Tuba-1c, Aldolase-B, alpha-fetoprotein, and Mmp2 (P > 0.05). miR-122 was higher in HCC, and miR-34a in RIF compared to controls (P < 0.05). miR-26b was lower in HCC compared to RIF, and the inverse was observed for miR-224 (P < 0.05). There was no difference among groups regarding miR-33a, miR-143, miR-155, miR-375 and miR-21 (P > 0.05). CONCLUSION RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.
- African genetic ancestry is associated with lower frequency of PNPLA3 G allele in non-alcoholic fatty liver in an admixed population(2022) CAVALCANTE, Lourianne Nascimento; PORTO, Jun; MAZO, Daniel; LONGATTO-FILHO, Adhemar; STEFANO, Jose Tadeu; LYRA, Andre Castro; CARRILHO, Flair Jose; REIS, Rui Manuel; ALVES, Venancio A. F.; SANYAL, Arun J.; OLIVEIRA, Claudia P.Introduction and objectives: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ances-try Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population.Methods: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplanta-tion. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyp-ing were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; a<0.05 was considered significant.Results: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerin-dian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 +/- 0.205 versus 0.105 +/- 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes.Conclusion: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.(c) 2022 Published by Elsevier Espana, S.L.U. on behalf of Fundacion Clinica Medica Sur, A.C. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
conferenceObject Strategies to eliminate hepatitis C virus infection in the Americas(2023) DIAZ, Luis Antonio; GARCIA, Sergio; KHAN, Rayan; AYARES, Gustavo; MONASTERIO, Javier Uribe; IDALSOAGA, Francisco; FUENTES, Eduardo; MEDEL, Maria Paz; RAMIREZ, Carolina; LAZO, Mariana; FERRECCIO, Catterina; MENDIZABAL, Manuel; DIRCHWOLF, Melisa; GUERRA, Patricia; OLIVEIRA, Claudia; PESSOA, Mario; ALVARES-DA-SILVA, Mario; SEBASTIANI, Giada; BRAHMANIA, Mayur; RAMJI, Alnoor; NIAZI, Mina; KO, Hin Hin; FELD, Jordan J.; RESTREPO, Juan Carlos; RAMIREZ, Wagner; ALFARO, Omar; CASTELLANOS-FERNANDEZ, Marlen; CARRERA, Enrique; AGUIRRE, Jose Roberto; CARDONA, Katherine Emilia Maldonado; SANCHEZ, Abel; SANCHEZ, Marco; ANDARA, Maria Teresa; CASTRO-NARRO, Graciela; CHAVEZ-TAPIA, Norberto Carlos; MENDEZ-SANCHEZ, Nahum; ADAMES, Enrique; LOMBARDO, Julissa; GIRALA, Marcos; MORAN, Elias; PADILLA, P. Martin; DIAZ-FERRER, Javier; TAGLE, Martin; MAINARDI, Victoria; HERNANDEZ, Nelia; MARTINEZ, Edmundo; ALVARADO-TAPIAS, Edilmar; ROBERT, Leon; HERNANDEZ-TEJERO, Maria; SICILIA, Mauricio Garcia Saenz De; ZHANG, Wei; BAJAJ, Jasmohan S.; TAPPER, Elliot; IZZY, Manhal; GISH, Robert G.; ATTAR, Bashar; COTTER, Thomas; KAMATH, Patrick S.; SINGAL, Ashwani; BATALLER, Ramon; MEZZANO, Gabriel; SOZA, Alejandro; LAZARUS, Jeffrey; ARRESE, Marco; ARAB, Juan Pablo- Interaction of Microbiome, Diet, and Hospitalizations Between Brazilian and American Patients With Cirrhosis(2022) ALVARES-DA-SILVA, Mario R.; OLIVEIRA, Claudia P.; FAGAN, Andrew; LONGO, Larisse; THOEN, Rutiane U.; ZITELLI, Patricia M. Yoshimura; FERREIRA, Renee M. Tanaka; MCGEORGE, Sara; SHAMSADDINI, Amirhossein; FARIAS, Alberto Q.; SIKAROODI, Masoumeh; GILLEVET, Patrick M.; BAJAJ, Jasmohan S.BACKGROUND & AIMS: Gut microbiota are affected by diet, country, and affect outcomes in cirrhosis. Western diets are associated with dysbiosis. Comparisons with other diets is needed. We aimed to compare cirrhosis patients from the United States with cirrhosis patients from Brazil with respect to diet, microbiota, and impact on hospitalizations. METHODS: Healthy controls and compensated/decompensated outpatients with cirrhosis from the United States and Brazil underwent dietary recall and stool for 16S ribosomal RNA sequencing. Demographics and medications/cirrhosis details were compared within and between countries. Patients with cirrhosis were followed up for 90-day hospitalizations. Regression for Shannon diversity was performed within cirrhosis. Regression for hospitalizations adjusting for clinical and microbial variables was performed. RESULTS: Model for end-stage liver disease (MELD), diabetes, ascites, and albumin were similar, but more Americans were men, had higher hepatic encephalopathy and alcohol/hepatitis C etiology, with lower nonalcoholic fatty liver disease than Brazilians. Brazilians had higher cereal, rice, and yogurt intake vs the United States. As disease progressed, cereals, rice/beans, coffee, and chocolate consumption was reduced. Microbial diversity was higher in Brazilians. Within cirrhosis, high diversity was related to Brazilian origin (P < .0001), age, and cereal intake (P = .05), while high MELD scores (P = .009) and ascites (P = .05) did the reverse. Regardless of stage, beneficial taxa and taxa associated with grant and yogurt intake were higher (Ruminococcaceae, Christensenellacae, and Prevotellaceae), while pathobionts (Porphyromonadaceae, Sutterellaceae, and Enterobacteriaceae) were lower in Brazilians. More Americans were hospitalized vs Brazilians (P = .002). On regression, MELD (P = .001) and ascites (P = .001) were associated with higher hospitalizations, while chocolate (P = .03) and Brazilian origin (P = .001) were associated with lower hospitalizations with/without microbiota inclusion. CONCLUSIONS: Brazilian cirrhotic patients follow a diet richer in cereals and yogurt, which is associated with higher microbial diversity and beneficial microbiota and could contribute toward lower hospitalizations compared with a Western-diet-consuming American cohort.