FABIOLA RABELO
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Hypolactasia is associated with insulin resistance in nonalcoholic steatohepatitis(2016) MAZO, Daniel Ferraz de Campos; MATTAR, Rejane; STEFANO, Jose Tadeu; SILVA-ETTO, Joyce Matie Kinoshita da; DINIZ, Marcio Augusto; DUARTE, Sebastiao Mauro Bezerra; RABELO, Fabiola; LIMA, Rodrigo Vieira Costa; CAMPOS, Priscila Brizolla de; CARRILHO, Flair Jose; OLIVEIRA, Claudia P.AIM To assess lactase gene (LCT)-13910C>T polymorphisms in Brazilian non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients in comparison with healthy controls. METHODS This was a transverse observational clinical study with NAFLD patients who were followed at the Hepatology Outpatient Unit of the Hospital das Clinicas, Sao Paulo, Brazil. The polymorphism of lactase non-persistence/ lactase persistence (LCT-13910C>T) was examined by PCR-restriction fragment length polymorphism technique in 102 liver biopsy-proven NAFLD patients (steatosis in 9 and NASH in 93) and compared to those of 501 unrelated healthy volunteers. Anthropometric, clinical, biochemical and liver histology data were analyzed. Continuous variables were compared using the t or Mann-Whitney tests, and categorical data were compared with the Fisher's exact test. Univariate logistic regression and multivariate logistic regression adjusted for gender and age were performed. RESULTS No differences in the LCT-13910 genotype frequencies were noted between the NAFLD patients (66.67% of the patients with steatosis were CC, 33.33% were CT, and none were TT; 55.91% of the patients with NASH were CC, 39.78% were CT, and 4.3% were TT; P = 0.941) and the healthy controls (59.12% were CC, 35.67% were CT, and 5.21% were TT) or between the steatosis and NASH patients. That is, the distribution of the lactase non-persistence/lactase persistence polymorphism (LCT-13910C>T) in the patients with NAFLD was equal to that in the general population. In the NASH patients, the univariate analysis revealed that the lactase nonpersistence (low lactase activity or hypolactasia) phenotype was associated with higher insulin levels (23.47 +/- 15.94 mu U/mL vs 15.8 +/- 8.33 mu U/mL, P = 0.027) and a higher frequency of insulin resistance (91.84% vs 72.22%, P = 0.02) compared with the lactase persistence phenotype. There were no associations between the LCT genotypes and diabetes (P = 0.651), dyslipidaemia (P = 0.328), hypertension (P = 0.507) or liver histology in these patients. Moreover, in the NASH patients, hypolactasia was an independent risk factor for insulin resistance even after adjusting for gender and age [OR = 5.0 (95%CI: 1.35-20; P = 0.017)]. CONCLUSION The LCT-13910 genotype distribution in Brazilian NAFLD patients was the same as that of the general population, but hypolactasia increased the risk of insulin resistance in the NASH patients.
- Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal(2015) CAVALCANTE, Lourianne Nascimento; STEFANO, Jose Tadeu; V, Mariana Machado; MAZO, Daniel F.; RABELO, Fabiola; SANDES, Kiyoko Abe; CARRILHO, Flair Jose; CORTEZ-PINTO, Helena; LYRA, Andre Castro; OLIVEIRA, Claudia P. deAIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnicgeographical differential frequencies (>= 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P < 0.05). RESULTS: In the Brazilian sample, NASH was significantly more frequent among the elderly patients with diabetes (NASH 56 +/- 1.1 years old vs S. Steatosis 51 +/- 1.5 years old, P = 3.7 x 10(-9)), dyslipidemia (NASH 63% vs S. Steatosis 37%, P = 0.009), higher fasting glucose levels (NASH 124 +/- 5.2 vs S. Steatosis 106 +/- 5.3, P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups. CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.
conferenceObject NADPH OXIDASE (NOX 4) AND P22PHOX GENE POLYMORPHISMS ARE ASSOCIATED WITH HUMAN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)(2014) RABELO, F.; STEFANO, J. T.; LIMA, R. V.; SEIXAS, M.; PATENTE, T.; VANNI, D.; CAVALEIRO, A. M.; MAZO, D. C.; CARRILHO, F. J.; CORREA-GIANNELLA, M. L.; OLIVEIRA, C.conferenceObject GENETIC ANCESTRY CHARACTERIZATION IN NAFLD PATIENTS FROM BRAZIL AND PORTUGAL(2014) CAVALCANTE, L. N.; STEFANO, J. T.; MACHADO, M.; RABELO, F.; MAZO, D. C.; ANGELO, A. L. D.; ABE-SANDES, K.; LYRA, L. G. C.; CARRILHO, F. J.; CORTEZ-PINTO, H.; LYRA, A. C.; OLIVEIRA, C. P.conferenceObject Comparison between Results of Hepatic Transient Elastography (fibroscan (R)) and Controlled Attenuation Parameter (cap (TM)) versus Liver Biopsy in NAFLD Patients(2013) VANNI, Denise S.; OLIVEIRA, Claudia P.; MAZO, Daniel F.; RABELO, Fabiola; STEFANO, Jose Tadeu; CARRILHO, Flair J.bookPart Doenças Hepáticas Causadas por Bactérias, Parasitas e/ou Fungos(2016) CALY, Wanda Regina; FARIAS, Alberto Queiroz; RABELO, Fabiola; BAPTISTA, Daniel Machado; CARRILHO, Flair José- S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis (vol 7, pg 553, 2013)(2013) MAZO, D. F.; OLIVEIRA, M. G. De; V, I. Pereira; COGLIATI, B.; STEFANO, J. T.; SOUZA, G. F. de; RABELO, F.; LIMA, F. R.; ALVES, V. A. Ferreira; CARRILHO, F. J.; OLIVEIRA, C. P. de
- 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.
- Hypocaloric high-protein diet improves clinical and biochemical markers in patients with nonalcoholic fatty liver disease (NAFLD)(2014) DUARTE, Sebastiao Mauro Bezerra; FAINTUCH, Joel; STEFANO, Jose Tadeu; OLIVEIRA, Maria Beatriz Sobral de; MAZO, Daniel Ferraz de Campos; RABELO, Fabiola; VANNI, Denise; NOGUEIRA, Monize Aydar; CARRILHO, Flair Jose; OLIVEIRA, Claudia Pinto Marques Souza deObjective: To investigate the role of hypocaloric high-protein diet, a prospective clinical study was conducted in NAFLD patients. Research methods and procedures: Pre-versus post-interventional data were analyzed in 48 stable NAFLD patients (submitted to a hypocaloric high-protein diet during 75 days. Variables included anthropometrics (body mass index/ BMI and waist circumference/WC), whole-body and segmental bioimpedance analysis and biochemical tests. Diet compliance was assessed by interviews every two weeks. Results: BMI, WC and body fat mass remained relatively stable (-1.3%, -1.8% and -2.5% respectively, no significance). HDL- cholesterol increased (P < 0.05) whereas total, LDL and VLDL cholesterol, triglycerides, aspartate aminotransferase/AST, gamma glutamyltransferase/GGT, alkaline phosphatase/AP, fasting blood glucose and glycated hemoglobin/HbA1c decreased (P < 0.05). When patients were stratified according to increase (22/48, 45.8%) and decrease (21/48, 43.8%) of BMI, association between weight decrease and liver benefit could be elicited in such circumstances for ALT, AP and AST/ALT ratio. No change could be demonstrated in patients who gained weight. Multivariate assessment confirmed that waist circumference, ferritin, triacylglycerol, and markers of glucose homeostasis were the most relevant associated with liver enzymes. Discussion: Ours results are consistent with the literature of calorie restriction in the management of NAFLD. Changes in lifestyle and weight loss are recommended for NAFLD patients. European guidelines also support this recommendation. Conclusion: This is the first study that demonstrated that a high protein, hypocaloric diet were associated with improvement of lipid profile, glucose homeostasis and liver enzymes in NAFLD independent on BMI decrease or body fat mass reduction.