JOSE TADEU STEFANO

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Índice h a partir de 2011
17
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

Resultados de Busca

Agora exibindo 1 - 10 de 25
  • article 13 Citação(ões) na Scopus
    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.
  • conferenceObject
    THE COMBINATION OF PROBIOTICS AND PREBIOTICS SUPPLEMENTATION IMPROVES LIPID METABOLISM, NAFLD AND OBESITY IN OB/OB MICE
    (2015) STEFANO, J. T.; TORRES, M. M.; PEREIRA, I. V. A.; JIMENEZ, D.; MUNTANELLI, B.; MALTA, F. M.; COGLIATI, B.; PINHO, J. R. R.; CARRILHO, F. J.; OLIVEIRA, C. P.
  • conferenceObject
    INTRATUMORAL INJECTION OF S-NITROSO-N-ACETYLCYSTEINE (SNAC) IN A RODENT MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)-RELATED HEPATOCELLULAR CARCINOMA (HCC)
    (2014) STEFANO, J. T.; TORRES, M. M.; PEREIRA, I. V. A.; COGLIATI, B.; OLIVEIRA, M. G. de; CHAMMAS, C.; CARRILHO, F. J.; OLIVEIRA, C. P.
  • article 103 Citação(ões) na Scopus
    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.
  • article 6 Citação(ões) na Scopus
    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.
  • article 2 Citação(ões) na Scopus
    Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
    (2022) GRANJA, S. C.; LONGATTO-FILHO, A.; CAMPOS, P. B. De; OLIVEIRA, C. P.; STEFANO, J. T.; MARTINS-FILHO, S. N.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; ALVARES-DA-SILVA, M. Reis; CARRILHO, F. J.; BALTAZAR, F.; ALVES, V. A. F.
    Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.
  • conferenceObject
    ELASTOGRAPHY AND CONTRAST-ENHANCED ULTRASONOGRAPHY IMPROVES EARLY DETECTION OF HEPATOCELLULAR CARCINOMA IN AN EXPERIMENTAL MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)
    (2012) CARVALHO, C. F.; CHAMMAS, M. C.; COGLIATTI, B.; STEFANO, J. T.; CARRILHO, F. J.; OLIVEIRA, C. P. M. S.
    Background and Aims: Early detection of focal hepatic lesions is a challenge for ultrasound scanning and becomes even greater in the presence of a diffuse parenchymal disease. Hepatocelular carcinoma is the fifth most common cancer in human being and is a recognized complication of advanced non-alcoholic steatohepatitis. This study aimed to evaluate the diagnostic performance of elastography and contrast-enhanced ultrasonography for early detection of hepatocellular lesions in an experimental model of non-alcoholic steatohepatitis (NASH). Methods: Adult Sprague-Dawley rats, weighing 250–300g, were fed a choline-deficient high fat diet (35% total fat, 54% trans fatty acid enriched) and simultaneously exposed to diethylnitrosamine (13–15mg/day) in drinking water during 16 weeks to induce NASH. Control group (n=10) received standard diet and water ad libitum . B-mode and Doppler ultrasonography was performed weekly in these experimental rats. The animals with NASH that developed focal liver lesions with suggestive malignancy were underwent elastography and contrast-enhanced ultrasonography, euthanized and liver nodules were assessment by histopathology. Tissue stiffness of the nodules on elastography were classified in negative (elastic strain) or positive (hard and no strain) comparing with surrounding liver parenchyma. Contrasted study classified focal lesions according to type of enhancement and wash out. Results: Elastograms of positive lesions showed area of high shear stiffness, which were indicative of malignancy confirmed on histology evaluation, with sensitivity of 100% and specificity of 90%. In the early phase, wash in was significantly associated with malignancy (sensitivity of 71% and specificity of 100%). Also wash out in the late phase was associated with malignancy, with sensitivity of 86% and specificity of 67%. Conclusions: 1. Both techniques allow making right diagnosis with high accuracy of well to moderately-differentiated hepatocellular carcinomas in an experimental model of NASH. 2. Elastography provided promising perspectives for the assessment of malignancy of focal hepatic lesions.
  • conferenceObject
    Cardiovascular risk and coronary artery calcium score after liver transplantation: study at fouth year
    (2017) LINHARES, L. M.; OLIVEIRA, C. P.; ALVARES-DA-SILVA, M. R.; STEFANO, J. T.; GEBRIM, E. M.; BARBEIRO, H. V.; BARBEIRO, D. F.; TERRABUIO, D. R.; ABDALA, E.; SORIANO, F. G.; CARRILHO, F. J.; FARIAS, A. Q.; AUGUSTO, L.; ALBUQUERQUE, C. D'
  • article 20 Citação(ões) na Scopus
    Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model
    (2015) STEFANO, J. T.; PEREIRA, I. V. A.; TORRES, M. M.; BIDA, P. M.; COELHO, A. M. M.; XERFAN, M. P.; COGLIATI, B.; BARBEIRO, D. F.; MAZO, D. F. C.; KUBRUSLY, M. S.; D'ALBUQUERQUE, L. A. C.; SOUZA, H. P.; CARRILHO, F. J.; OLIVEIRA, C. P.
    Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg.kg(-1).day(-1) by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1 alpha) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1 alpha and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1 alpha expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.
  • conferenceObject
    Combination of long term N-Acetylcysteine and Ursodeoxycolic Acid in NASH: a multicenter randomized control trial
    (2017) OLIVEIRA, C. P.; COTRIM, H. P.; CRISTINA, A.; SIQUEIRA, G.; SALGADO, A. L. A.; STEFANO, J. T.; BRIZOLLA, P.; MATTOS, L.; MARTINS, A. H. B.; ANDRADE, A. R.; SCIUTO, R.; FREITAS, L. A.; ALVES, V. A. F.; CARRILHO, F. J.; PARISE, E. R.