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
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conferenceObject Integrative Molecular Profiling of Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma(2018) TORRECILLA, Sara; PINYOL, Roser; WEI-QIANG, Leow; WANG, Huan; MOEINI, Agrin; MONTIRONI, Carla; BASSAGANYAS, Laia; ANDREU-OLLER, Carmen; OLIVEIRA, Claudia P. M. S.; ALVES, Venancio A. F.; LACHENMAYER, Anja; ROESSLER, Stephanie; MINGUEZ, Beatriz; SCHIRMACHER, Peter; BOFFETTA, Paolo; DUFOUR, Jean-Francois; THUNG, Swan N.; UZILOV, Andrew; CARRILHO, Flair Jose; CHANG, Charissa Y.; SIA, Daniela; LLOVET, Josep M.- Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study(2018) DUARTE, S. M. B.; STEFANO, J. T.; MIELE, L.; PONZIANI, F. R.; SOUZA-BASQUEIRA, M.; OKADA, L. S. R. R.; COSTA, F. G. de Barros; TODA, A. K.; MAZO, D. F. C.; SABINO, E. C.; CARRILHO, F. J.; GASBARRINI, A.; OLIVEIRA, C. P.Background and Aim: The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. Methods and Results: We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis >= F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. Conclusion: Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.
- Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients(2018) LINHARES, L. M. C.; OLIVEIRA, C. P.; ALVARES-DA-SILVA, M. R.; STEFANO, J. T.; BARBEIRO, H. V.; BARBEIRO, D. F.; TERRABUIO, D. R. B.; ABDALA, E.; SORIANO, F. G.; CARRILHO, F. J.; FARIAS, A. Q.; SIDDIQUI, M. S.; D'ALBUQUERQUE, L. A. C.Background. Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). Methods. This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). Results. The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 +/- 0.44 ng/mL to 9.10 +/- 5.82 ng/mL (P < .001) and 0.23 +/- 0.09 ng/mL to 2.7 +/- 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 +/- 0.07 ng/mL to 3.46 +/- 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 +/- 40.7 ng/mL at entry to 91.5 +/- 143.6 ng/mL at end of study (P < .001). Conclusion. No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.
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.- Noninvasive mapping of fibrosis and inflammation in nonalcoholic fatty liver disease: isolating fibrogenesis in the Space of Disse with MRI R2 multicomponent relaxometry(2018) CLARK, P.; CHUA-ANUSORN, W.; OLIVEIRA, C.; ROCHA, M.; CARRILHO, F. J.; LIMA, F.; ALVES, V.; OLIVEIRA, B.; FILHO, H. L.
- Iron-Overload Evaluation by Noninvasive Methods in Patients with Nonalcoholic Fatty Liver Disease, Overweight, and Hyperferritinemia(2018) BRANISSO, Paula P. F.; OLIVEIRA, Claudia P.; LEAO FILHO, Hilton M.; SANTOS, Aritania; LIMA, Fabiana R.; MANCINI, Marcio; CARRILHO, Flair Jose; ROCHA, Manoel; CERCATO, Cintia
conferenceObject The Impact of HEV Infection on the Disease Severity of Patients with Chronic Hepatitis C(2018) ZITELLI, Patricia; GOMES-GOUVEA, Michele; MAZO, Daniel; PINHO, Joo Renato R.; ALVES, Venancio A. F.; TANIGAWA, Ryan Yukimatsu; OLIVEIRA, Claudia S.; CARRILHO, Flair Jose; PESSOA, Mario GuimaraesconferenceObject Plasma Proteomic Signature in Patients with Nash Treated with OMEGA-3: Perspectives of Knowing Mechanism of Action.(2018) OKADA, Livia Samara Reis Rodrigues; OLIVEIRA, Claudia P. M. S.; STEFANO, Jose Tadeu; NOGUEIRA, Monize Aydar; CORDEIRO, Fernanda Bertucce; ALVES, Venancio A. F.; TORRINHAS, Raquel Suzana; CARRILHO, Flair Jose; WAITZBERG, Dan Linetzky- Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight(2018) OKADA, Livia Samara dos Reis Rodrigues; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; NOGUEIRA, Monize Aydar; SILVA, Ismael Dale Cotrim Guerreiro da; CORDEIRO, Fernanda Bertucce; ALVES, Venancio Avancini Ferreira; TORRINHAS, Raquel Susana; CARRILHO, Flair Jose; PURI, Puneet; WAITZBERG, Dan L.Background & aims: Currently there is no FDA-approved therapy for nonalcoholic steatohepatitis (NASH). Increased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio can induce endoplasmic reticulum (ER) stress and mitochondrial dysfunction that characterize NASH. Our recent study with n-3 PUFA showed improvement in individual histologic parameters like steatosis, ballooning and lobular inflammation. We hypothesized that n-3 PUFA therapy mediated improvement in histologic parameters is modulated by lipidomic and proteomic changes. Methods: We therefore evaluated hepatic proteomic and plasma lipidomic profiles before and after n-3 PUFA therapy in subjects with NASH. In a double-blind, randomized, placebo-controlled trial, patients with NASH received 6-month treatment with n-3 PUFA (0.945 g/day [64% alpha-linolenic (ALA), 21% eicosapentaenoic (EPA), and 16% docosahexaenoic (DHA) acids]). Paired liver biopsy and plasma collected before and after-n-3 PUFA therapy were assessed using mass spectrometry and gas chromatography for hepatic proteomics and plasma lipidomics. Data were matched to UniProt and LIPID MAPS database, respectively. Cytoscape software was used to analyze functional pathways. Twenty-seven NASH patients with paired liver histology and plasma before and after n-3 PUFA treatment were studied. Results: Treatment with n-3 PUFA significantly increased ALA, EPA, and glycerophospholipids, and decreased arachidonic acid (p < 0.05 for all). Further, proteomic markers of cell matrix, lipid metabolism, ER stress and cellular respiratory pathways were also modulated. Interestingly, these alterations reflected functional changes highly suggestive of decreased cellular lipotoxicity potential; reduced ER proteasome degradation of proteins and induction of chaperones; and a shift in cell energy homeostasis towards mitochondrial beta-oxidation. Conclusion: Six-month treatment with omega-3 PUFAs significantly improved hepatic proteomic and plasma lipidomic markers of lipogenesis, endoplasmic reticulum stress and mitochondrial functions in patients with NASH.
- Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population(2018) RABELO, Fabiola; STEFANO, Jose Tadeu; CAVALEIRO, Ana Mercedes; LIMA, Rodrigo Vieira Costa; MAZO, DanielFerraz de Campos; CARRILHO, Flair Jose; CORREA-GIANNELLA, Maria Lucia; OLIVEIRA, Claudia P.Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease (NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms (SNPs) in the regulatory region of genes encoding NADPH oxidase 4 (NOX4) and p22phox (CYBA) in NAFLD. Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis (n =27); nonalcoholic steatohepatitis (NASH) (n =180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA (unregistered) and NOX4 (rs3017887) were determined by direct sequencing of PCR. Results: Associations of CYBA-675 T/A with high-density lipoprotein (HDL) (TT vs TA vs AA; P <0.01) and triglycerides (TGL) (TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4 (rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase (ALT) (CA + AA vs CC; P=0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus (66.9% vs 37.5%, P < 0.01) and those who were more obese (32.2 vs 29.0 kg/m(2), P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH. Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.