DANIEL FERRAZ DE CAMPOS MAZO

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina

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Autor: CARRILHO, Flair J. ×

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  • article 23 Citação(ões) na Scopus
    S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis
    (2013) MAZO, Daniel F. C.; OLIVEIRA, Marcelo G. de; PEREIRA, Isabel V. A.; COGLIATI, Bruno; STEFANO, Jose T.; SOUZA, Gabriela F. P. de; RABELO, Fabiola; LIMA, Fabiana R.; ALVES, Venancio A. Ferreira; CARRILHO, Flair J.; OLIVEIRA, Claudia P. M. S. de
    S-Nitroso-N-acetylcysteine (SNAC) is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH) induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2), transforming growth factor beta-1 [TGF beta-1], collagen-1 alpha, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90) were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGF beta-1, and collagen-1 alpha. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH.
  • article 16 Citação(ões) na Scopus
    Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C
    (2017) PARANAGUA-VEZOZZO, Denise C.; ANDRADE, Adriana; MAZO, Daniel F. C.; NUNES, Vinicius; GUEDES, Ana L.; RAGAZZO, Taisa G.; MOUTINHO, Renata; NACIF, Lucas S.; ONO, Suzane K.; ALVES, Venancio A. F.; CARRILHO, Flair J.
    AIM To determine the sensitivity and specificity of liver stiffness measurement (LSM) and serum markers (SM) for liver fibrosis evaluation in chronic hepatitis C. METHODS Between 2012 and 2014, 81 consecutive hepatitis C virus (HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography (TE) [FibroScan (R)/ARFI technology (Virtual Touch (R))] and SM [FIB-4/aspartate aminotransferase-to-platelet ratio index (APRI)]. The diagnostic performance of these tests was assessed using receiver operating characteristic curves. The optimal cut-off levels of each test were chosen to define fibrosis stages F >= 2, F >= 3 and F = 4. The Kappa index set the concordance analysis. RESULTS Fifty point six percent were female and the median age was 51 years (30-78). Fifty-six patients (70%) were treatment-naive. The optimal cut-off values for predicting F >= 2 stage fibrosis assessed by TE were 6.6 kPa, for acoustic radiation force impulse (ARFI) 1.22 m/s, for APRI 0.75 and for FIB-4 1.47. For F >= 3 TE was 8.9 kPa, ARFI was 1.48 m/s, APRI was 0.75, and FIB-4 was 2. For F = 4, TE was 12.2 kPa, ARFI was 1.77 m/s, APRI was 1.46, and FIB-4 was 3.91. The APRI could not distinguish between F2 and F3, P = 0.92. The negative predictive value for F = 4 for TE and ARFI was 100%. Kappa index values for F >= 3 METAVIR score for TE, ARFI and FIB-4 were 0.687, 0.606 and 0.654, respectively. This demonstrates strong concordance between all three screening methods, and moderate to strong concordance between them and APRI (Kappa index = 0.507). CONCLUSION Given the costs and accessibility of LSM methods, and the similarity with the outcomes of SM, we suggest that FIB-4 as well as TE and ARFI may be useful indicators of the degree of liver fibrosis. This is of particular importance to developing countries.
  • article 15 Citação(ões) na Scopus
    Protease Inhibitor Resistance Mutations in Untreated Brazilian Patients Infected with HCV: Novel Insights about Targeted Genotyping Approaches
    (2014) CARVALHO, Isabel M. V. G. de; ALVES, Rafael; SOUZA, Polyana A. Vasconcelos-Medeiros de; SILVA, Edvaldo F. da; MAZO, Daniel; CARRILHO, Flair J.; QUEIROZ, Artur T. L.; PESSOA, Mario G.
    Several new direct-acting antiviral (DAA) drugs are being developed or are already approved for the treatment of chronic hepatitis C virus (HCV) infection. HCV variants presenting drug-resistant phenotypes were observed both in vitro and during clinical trials. The aim of this study was to characterize amino acid changes at positions previously associated with resistance in the NS3 protease in untreated Brazilian patients infected with HCV genotypes 1a and 1b. Plasma samples from 171 untreated Brazilian patients infected with HCV were obtained from the Department of Gastroenterology of Clinics Hospital (HCFMUSP) in Sao Paulo, Brazil. Nested PCR and Sanger sequencing were used to obtain genetic information on the NS3 protein. Bioinformatics was used to confirm subtype information and analyze frequencies of resistance mutations. The results from the genotype analysis using non-NS3 targeted methods were at variance with those obtained from the NS3 protease phylogenetic analyses. It was found that 7.4% of patients infected with HCV genotype 1a showed the resistance-associated mutations V36L, T54S, Q80K, and R155K, while 5.1% of patients infected with HCV genotype 1b had the resistance-associated mutations V36L, Q41R, T54S, and D168S. Notably, codons at positions 80 and 155 differed between samples from Brazilian patient used in this study and global isolates. The present study demonstrates that genotyping methods targeting the NS3 protein showed a difference of results when compared to mainstream methodologies (INNO-LiPA and polymerase sequencing). The resistance mutations present in untreated patients infected with HCV and codon composition bias by geographical location warrant closer examination. (C) 2014 Wiley Periodicals, Inc.
  • article 4 Citação(ões) na Scopus
    HAV and HBV seroprevalence in 1,000 patients with chronic HCV infection in a Tertiary Care Center in Sao Paulo, Brazil
    (2016) SILVA, Edvaldo F. da; MAZO, Daniel F.; OLIVEIRA, Claudia P.; MEDEIROS, Roseane P.; CARRILHO, Flair J.; PESSOA, Mario G.
    Background. Patients with chronic HCV infection and superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) have higher morbidity and mortality when compared with those without HCV infection. Therefore, HAV and HBV active immunization has become mandatory in this population and hence their serological markers must be determined. The aim of this study was to evaluate the prevalence of serological markers of HAV and HBV infection in patients with chronic HCV. Material and methods: One thousand chronic HCV patients at the University of Sao Paulo School of Medicine were evaluated for the prevalence of serological markers of HAV and HBV infection. Results: Anti-HAV IgG was positive in 92.3% of patients. When stratified by age, anti-HAV IgG was found in 61% of patients between 20-29 years, 70% on patients between 30-39 years, 85% on patients between 40-49 years, 94% on patients between 50-59 years, and in 99% on patients over 60 years of age. Anti-HBc IgG was positive in 244 patients (24%). Stratified by age, in 4.3% of patients between 20-29 years, 17% 30-39 years, 21% 40-49 years, 24% 50-59 years, and in 28% of patients over 60 years. Of the 244 anti-HBc IgG positive patients, 0.8% were HBsAg positive, 8.5% were anti-HBc IgG isolated and 16% were also anti-HBs positive. Conclusions: In conclusion, the prevalence of anti-HAV IgG was similar to the general Brazilian population. However, anti-HBc IgG was higher in our patients, when compared to general population of Western countries, emphasizing the importance of immunization programs for this population.
  • article 0 Citação(ões) na Scopus
    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
    Hepatitis A and B Seroprevalence in 1000 Patients with Chronic HCV Infection on a Tertiary Care Center in Brazil
    (2012) SILVA, Edvaldo F.; MAZO, Daniel F.; OLIVEIRA, Claudia P.; MEDEIROS, Roseane P.; CARRILHO, Flair J.; PESSOA, Mario G.
  • conferenceObject
    Molecular Characterization of the Fecal Microbiome in Brazilian Obese NASH patients compared to lean healthy controls.
    (2015) OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; RIBEIRO, Roberto M.; DUARTE, Sebastiao M.; RODRIGUES, Livia; CAMPOS, Priscila B.; COSTA, Fernando G.; MAZO, Daniel F.; CARRILHO, Flair J.; SABINO, Ester C.
  • article 0 Citação(ões) na Scopus
    Serum B-type natriuretic peptide in the initial workup of patients with new onset ascites: A diagnostic accuracy study (vol 59, pg 1043. 2014)
    (2014) FARIAS, Alberto Q.; SILVESTRE, Odilson M.; GARCIA-TSAO, Guadalupe; SEGURO, Luis F. B. da Costa; MAZO, Daniel F. de Campos; BACAL, Fernando; ANDRADE, Jose L.; GONCALVES, Luciana L.; STRUNZ, Celia; RAMOS, Danusa S.; POLLI, Demerson; PUGLIESE, Vincenzo; RODRIGUES, Ana C. T.; FURTADO, Meive S.; CARRILHO, Flair J.; D'ALBUQUERQUE, Luiz A. C.
  • article 6 Citação(ões) na Scopus
    The role of PNPLA3 and TM6SF2 polymorphisms on liver fibrosis and metabolic abnormalities in Brazilian patients with chronic hepatitis C
    (2021) OLIVEIRA, Arthur Ivan N.; MALTA, Fernanda M.; ZITELLI, Patricia Momoyo Y.; SALLES, Ana Paula M.; GOMES-GOUVEA, Michele S.; NASTRI, Ana Catharina S.; PINHO, Joao Renato R.; CARRILHO, Flair J.; OLIVEIRA, Claudia P.; MENDES-CORREA, Maria Cassia; PESSOA, Mario G.; MAZO, Daniel F.
    BackgroundDespite the growing body of knowledge about TM6SF2 and PNPLA3 polymorphisms in non-alcoholic fatty liver disease, their influence in the spectrum of HCV liver disease is not yet fully defined. Besides that, admixed populations, such as Brazilians, were not included in most of the studies.MethodsThis cross-sectional study enrolled 365 treatment-naive patients with HCV and 134 healthy individuals. TM6SF2 (rs58542926 c.499C>T) and PNPLA3 (rs738409 c.444C>G) polymorphisms were evaluated regarding their association with clinical and laboratory data, histological liver steatosis and fibrosis, and with components of the metabolic syndrome.ResultsIn HCV subjects, the frequencies of TM6SF2 CC and CT+TT were 89% and 11%, while PNPLA3 frequencies of CC and CG+GG were 51.4% and 48.6%. In the univariate logistic regression analysis, the TM6SF2 CT+TT genotype in HCV was associated with significant liver fibrosis (p=0.047; OR 1.953; 95% CI 1.009-3.788). In comparison to the CT+TT genotype, the TM6SF2 CC genotype in HCV was associated with older age (p=0.002), higher frequency of arterial hypertension (p=0.032), obesity (p=0.030), metabolic syndrome (p=0.014) and lower total cholesterol levels (p=0.036). The PNPLA3 GG subjects had lower body mass index than CG/ CC individuals (p=0.047). None of the polymorphisms, or their combinations, was independently associated with hepatic steatosis or fibrosis. On the other hand, older age, lower serum levels of total cholesterol, and higher serum levels of alanine aminotransferase and alkaline phosphatase were associated with liver fibrosis in the multivariate logistic regression analysis.ConclusionIn this evaluation of an admixed HCV population, neither TM6SF2 nor PNPLA3 polymorphisms were independently associated with hepatic steatosis or fibrosis. Other factors seem more influential than these specific polymorphisms in isolation. More studies are warranted to clarify the role of the TM6SF2 and PNPLA3 polymorphisms in Brazilians with HCV.
  • article 1 Citação(ões) na Scopus
    Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study
    (2021) LOURENCO, Mariana Sandoval; ZITELLI, Patricia Momoyo Y.; CUNHA-SILVA, Marlone; OLIVEIRA, Arthur Ivan N.; LIMA, Roque Gabriel Rezende de; OLIVEIRA, Souza Evandro de; OLIVEIRA, Claudia P.; SEVA-PEREIRA, Tiago; CARRILHO, Flair J.; PESSOA, Mario G.; MAZO, Daniel F.
    OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir +/- ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p.=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p.=0.027). SVR was associated with improvement in CP (p<0.0001) and MELD scores (p.=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p.=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised.