JOSE TADEU STEFANO
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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- MTP-493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients(2012) SIQUEIRA, E. R. F.; OLIVEIRA, C. P. M. S.; CORREA-GIANNELLA, M. L.; STEFANO, J. T.; CAVALEIRO, A. M.; FORTES, M. A. H. Z.; MUNIZ, M. T. C.; SILVA, F. S.; PEREIRA, L. M. M. B.; CARRILHO, F. J.The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.
- Randomized clinical trial: benefits of aerobic physical activity for 24 weeks in postmenopausal women with nonalcoholic fatty liver disease(2016) REZENDE, Rosamar E. F.; DUARTE, Sebastiao M. B.; STEFANO, Jose T.; ROSCHEL, Hamilton; GUALANO, Bruno; PINTO, Ana L. de Sa; VEZOZZO, Denise C. P.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.Objective: The aim of the study was to evaluate the effectiveness of aerobic physical activity in reducing the frequency of hepatic steatosis and metabolic and cardiovascular risk in postmenopausal women with nonalcoholic fatty liver disease (NAFLD). Methods: Forty sedentary postmenopausal women (mean age 55.3 +/- 8.0 y) with biopsy-proven NAFLD were randomly divided into two groups: an exercising group (19 participants) and a control group (nonexercising, 21 participants). The exercise group underwent a supervised aerobic physical activity program of 120 min/wk for 24 weeks. The anthropometric parameters; body composition; hepatic, lipid, and glycemic profiles; homeostasis model assessment of insulin resistance index; cytokines; transient elastography (FibroScan; liver stiffness/controlled attenuation parameter); and cardiopulmonary exercise test were evaluated at baseline and after 24 weeks of protocol. Results: At baseline there were no significant differences in anthropometric, metabolic, and inflammatory parameters-stiffness and liver fat content by FibroScan between the groups. After 24 weeks, we observed a decrease of waist circumference, an increase of high-density lipoprotein cholesterol levels (P < 0.05), and improved cardiopulmonary functional capacity in the exercise group. In addition, the controlled attenuation parameter analysis showed no significant decrease of hepatic steatosis in the exercise group. With regard to the systemic inflammation, there were, however, no significant differences in the cytokines between the groups. Conclusions: An aerobic physical activity program of 24 weeks in NAFLD postmenopausal women showed improvement in some variables such as waist circumference, high-density lipoprotein cholesterol, and cardiopulmonary performance that may be beneficial in improving cardiovascular risk factors in this population.
- 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.
- 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.
- Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease(2011) PEREIRA, Isabel V. A.; STEFANO, Jose T.; OLIVEIRA, Claudia P. M. S.Nonalcoholic fatty liver disease is currently one of the most common forms of liver disease, covering cases from simple steatosis without inflammation, to cases of steatohepatitis and fibrosis, and may lead to liver cirrhosis and hepatocellular carcinoma. The pathophysiology of nonalcoholic fatty liver disease is based on multiple events; changes in the secretion of lipoproteins can lead to steatosis. Liver lipid secretion is mediated by apoB100 and microsomal triglyceride transfer protein (MTP). The pharmacological suppression of MTP is suggested as a possible treatment for hyperlipidemia, although the upregulation of this protein can be a treatment for nonalcoholic steatohepatitis.
- Microbiota and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH)(2019) DUARTE, Sebastiao M. B.; STEFANO, Jose Tadeu; OLIVEIRA, Claudia P.Genetic predisposition, the intestinal microbiota (IM) and environmental factors, such as sedentary lifestyle and inadequate diet, should be considered as critical factors for the development of nonalcoholic fatty liver disease (NAFLD). Recently, some studies have demonstrated an association between dysbiosis and NAFLD; however, the exact mechanisms that lead to intestinal membrane damage, bacterial translocation and inflammation are not well elucidated. Due to the relevance of this theme, the IM and its metabolites have received special attention in recent years in an attempt to better understand the mechanisms related to the prevention, physiopathology, and treatment of NAFLD. In this paper, we provide a review of the human IM and its role in diet, obesity, and the development/progression of NAFLD/NASH, as well as the use of prebiotics and probiotics in the modulation of IM. (C) 2019 Fundacion Clinica Medica Sur, A.C.
- Genetic polymorphisms and oxidative stress in non-alcoholic steatohepatitis (NASH): A mini review(2015) OLIVEIRA, Claudia P.; STEFANO, Jose TadeuNon-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease, thus becoming an epidemic in the Western world with a major impact on public health. NAFLD encompasses a large spectrum of disease ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and may progress to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The role of genetic polymorphisms is not clear. Evidence supports the hypothesis that genetic factors are involved in the predisposition to NAFLD, and thus should emphasize the polygenic nature of the disease as a limiting factor in these studies. However, the polymorphic allele associated with increased hepatic steatosis appears to be associated with various different combinations of phenotypes, including increase or decrease of the biochemical and clinical parameters. It is possible that SNPs in genes involved in excessive fatty acid oxidation would predispose to NASH. On the other hand, the SNPs could determine the inadequate mitochondrial overload during times of excessive FFA supply. However due to the multiple hits involving some pathways, a brief review of genetic variants on mediators of oxidative stress, inflammation and lipid metabolism pathways is presented. It is clear that the discovery of genetic and environmental associations, robust enough to direct the treatment and to trace specific prevention strategies would only be possible with studies examining the susceptibility of NAFLD in a number of individuals considerably higher than assessed so far. These studies need a large number of well phenotyped cases and controls and certainly require national and international collaboration.
- 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.
- Effects of Hepatitis C virus on cardiovascular risk in infected patients: A comparative study(2013) OLIVEIRA, C. P. M. S.; KAPPEL, C. R.; SIQUEIRA, E. R.; LIMA, V. M. R.; STEFANO, J. T.; MICHALCZUK, M. T.; MARINI, S. S.; BARBEIRO, H. V.; SORIANO, F. G.; CARRILHO, F. J.; PEREIRA, L. M. M. B.; ALVARES-DA-SILVA, M. R.The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-alpha) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-alpha) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-alpha/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-alpha, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naive and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF).