FLAIR JOSE CARRILHO

(Fonte: Lattes)
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Lattes
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Departamento de Gastroenterologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder

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Revista / Livro: Annals of Hepatology ×

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  • article 44 Citação(ões) na Scopus
    Epidemiology of HCC in Brazil: incidence and risk factors in a ten-year cohort
    (2014) PARANAGUA-VEZOZZO, Denise C.; ONO, Suzane K.; ALVARADO-MORA, Monica V.; FARIAS, Alberto Q.; CUNHA-SILVA, Marlone; FRANCA, Joao I. D.; ALVES, Venancio A. F.; SHERMAN, Morris; CARRILHO, Flair Jose
    Background and aim. The lack of information about hepatocellular carcinoma (HCC) in Brazil weakens health policy in preventing deaths from the illness. The aim of this study was to establish the cumulative incidence and the risk factors for hepatocellular carcinoma development in patients under a surveillance program. Material and methods. 884 patients with compensated cirrhosis were prospectively followed up for at least five years, from August 1998 until August 2008, with at least one annual ultrasonography liver examination and serum alpha fetoprotein (AFP) measurement. Results. Among 884 patients, 72 (8.1%) developed a tumor with a median follow up of 21.4 months. In the hepatocellular carcinoma group, hepatitis C virus infection was the major etiological factor (65.3%), 56.9% (41/72) were male and the mean average age was 57 +/- 10 years. The annual incidence of hepatocellular carcinoma was 2.9%. 79.2% (57/72) of HCCs were detected within Milan Criteria, and the mean survival time was 52.3 months, significantly higher than for those outside Milan, with a mean time of 40.6 months (p = 0.0003). Conclusion. The annual incidence of HCC among this large series of Brazilian cirrhotic patients was around 2.9% with a detection rate of 8.1%, or a cumulative incidence rate over five years of 14.3%. The three variables related to HCC risk were low serum albumin [HR: 0.518 (0.46-0.78)], high AFP > 20 ng/mL [HR: 3.16 (1.86-5.38)], and ethnicity (Brazilian-East Asian descendants vs. other mixed Brazilian ethnicities) [HR: 2.86 (1.48-5.53)].
  • article 26 Citação(ões) na Scopus
    Impact of the severity of end-stage liver disease in cardiac structure and function
    (2013) SILVESTRE, Odilson Marcos; BACAL, Fernando; RAMOS, Danusa de Souza; ANDRADE, Jose L.; FURTADO, Meive; PUGLIESE, Vincenzo; BELLETI, Elisangela; ANDRAUS, Wellington; CARRILHO, Flair Jose; D'ALBUQUERQUE, Luiz Augusto Carneiro; FARIAS, Alberto Queiroz
    Background. The impact of end-stage liver disease (ESLD) in cardiac remodeling of patients with cirrhosis is unknown. Our aim was to correlate the severity of ESLD with morphologic and functional heart changes. Material and methods. 184 patients underwent a protocol providing data on the severity of ESLD and undergoing echocardiography to assess the diameters of the left atrium and right ventricle; the systolic and diastolic diameters of the left ventricle, interventricular septum, and posterior wall of the left ventricle; systolic pulmonary artery pressure; ejection fraction; and diastolic function. Severity of ESLD was assessed by the Model for End-Stage Liver Disease (MELD) score. Results. Left-atrial diameter (r = 0.323; IC 95% 0.190-0.455; p < 0.001), left-ventricular diastolic diameter (r = 0.177; IC 95% 0.033-0.320; p = 0.01) and systolic pulmonary artery pressure (r = 0.185; IC 95% 0.036-0.335; p = 0.02) significantly correlated with MELD score. Patients with MELD 16 had significantly higher left-atrial diameter and systolic pulmonary artery pressure, compared with patients with MELD scores < 16 points. Conclusions. Changes in cardiac structure and function correlate with the severity of ESLD.
  • article 28 Citação(ões) na Scopus
    Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure
    (2019) MENDES, Erica Araujo; PILGER, Denise Regina Bairros de; NASTRI, Ana Catharina de Seixas Santos; MALTA, Fernanda de Mello; PASCOALINO, Bruno dos Santos; D'ALBUQUERQUE, Luiz Augusto Carneiro; BALAN, Andrea; JR, Lucio Holanda Gondim de Freitas; DURIGON, Edison Luis; CARRILHO, Flair Jose; PINHO, Joao Renato Rebello
    Introduction and objectives: Direct antiviral agents (DAAs) are very efficient in inhibiting hepatitis C virus and might be used to treat infections caused by other flaviviruses whose worldwide detection has recently increased. The aim of this study was to verify the efficacy of DAAs in inhibiting yellow fever virus (YFV) by using drug repositioning (a methodology applied in the pharmaceutical industry to identify new uses for approved drugs). Materials and methods: Three DAAs were evaluated: daclatasvir, sofosbuvir and ledipasvir or their combinations. For in vitro assays, the drugs were diluted in 100% dimethyl sulfoxide. Vaccine strain 17D and a 17D strain expressing the reporter fluorescent protein were used in the assays. A fast and reliable cell-based screening assay using Vero cells or Huh-7 cells (a hepatocyte-derived carcinoma ell line) was carried out. Two patients who acquired yellow fever virus with acute liver failure were treated with sofosbuvir for one week as a compassionate use. Results: Using a high-content screening assay, we verified that sofosbuvir presented the best antiviral activity against YFV. Moreover, after an off-label treatment with sofosbuvir, the two female patients diagnosed with yellow fever infection displayed a reduction in blood viremia and an improvement in the course of the disease, which was observed in the laboratory medical parameters related to disease evolution. Conclusions: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use. These results offer insights into the role of nonstructural protein 5 (NS5) in YFV inhibition and suggest that nonstructural proteins may be explored as drug targets for YFV treatment. (C) 2019 Fundacion Clinica Medica Sur, A.C.
  • article 38 Citação(ões) na Scopus
    The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib
    (2017) BRANCO, Fernanda; ALENCAR, Regiane S. M.; VOLT, Fernanda; SARTORI, Giovana; DODE, Andressa; KIKUCHI, Luciana; TANI, Claudia M.; CHAGAS, Aline L.; PFIFFER, Tulio; HOFF, Paulo; CARRILHO, Flair J.; MATTOS, Angelo Alves de
    Background and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response , which can be eavaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil, Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database Results. Cirrhosis was present in 94% of patients, 85.6% were child-pugh A, 80.3%BCLC-C,81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1. The median duration of treatment was 10.1 months (range: 0.1-47 months). The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%). The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.
  • article 2 Citação(ões) na Scopus
    m-RECIST at 1 month and Child A are survival predictors after percutaneous ethanol injection of hepatocellular carcinoma
    (2014) SILVA, Mauricio F.; CARRILHO, Flair J.; PARANAGUA-VEZOZZO, Denise C.; CAMPOS, Luciana T.; NACIF, Lucas S.; DINIZ, Marcio A.; FARIAS, Alberto Q.; ALVES, Venancio A. F.; D'ALBURQUERQUE, Luis A. C.; ONO, Suzane K.
    Background and aims. Percutaneous ethanol injection (PEI) is a well-established therapeutic option in patients with cirrhosis and hepatocellular carcinoma (HCC). The modified-Response Evaluation Criteria in Solid Tumors (m-RECIST) are an important tool for the assessment of HCC response to therapy. The aim was to evaluate whether HCC response according to the m-RECIST criteria could be an effective predictor of Long-term survival in Barcelona Clinic Liver Cancer (BCLC) stage 0 and A HCC patients undergoing PEI. Material and methods. 79 patients were followed-up for median time of 26.8 months. HCC diagnosis was based on the,current guidelines of the American Association for Study of the Liver Diseases (AASLD) and European Association for Study of the Liver (EASL). Patient survival was calculated from the first PEI session to the end of the follow-up. Results. The 1-, 3-, and 5-year overall survival rates were 79, 48 and 37%, respectively. In the multivariate analysis, Child-Pugh-Turcotte (CPT) (p = 0.022) and the response to m-RECIST criteria (p = 0.016) were associated with patient survival. CPT A patients who achieved Complete Response (CR) 1 month after PEI presented a 5-year survival rate of 55%. By contrast, the worst scenario, the group with CPT B but without CR had a 5-year survival rate of 9%, while the group with either CPT A or CR as a survival predictor had a 5-year survival rate of 31%. In conclusion, in BCLC stage 0 and A HCC-patients, m-RECIST at 1 month and Child A may predict survival rates after PEI.
  • article 22 Citação(ões) na Scopus
    Usefulness of collagen type IV in the detection of significant liver fibrosis in nonalcoholic fatty liver disease
    (2021) STEFANO, Jose Tadeu; GUEDES, Laura Vilar; SOUZA, Arthur Alencar Arrais de; VANNI, Denise Siqueira; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair Jose; LARGURA, Alvaro; ARRESE, Marco; OLIVEIRA, Claudia P.
    Introduction/aims: Liver fibrosis assessment is a key issue in the evaluation of nonalcoholic fatty liver disease (NAFLD) patients. In the present study, we aimed to validate a noninvasive marker panel to assess significant and advanced fibrosis in these patients. Method: 126 biopsy-proven NAFLD patients were included. NAFLD diagnosis was based on histological criteria. Fibrosis stages were determined according to NASH-Clinical Research Network criteria. Clinical and laboratorial data were collected during the interval of three months before or after liver biopsy. Histological fibrosis stages were classified as significant fibrosis (F2-F4) and advanced fibrosis (F3-F4). Five serum biomarkers [hyaluronic acid (HA), collagen type IV (cIV), procollagen type III (PC III), laminin (LN) and cholylglycine (CG)] were assessed by chemiluminescence immunoassays. Results: Most patients were female (61.61%), mean age: 55.7 +/- 9.13 years old and mean BMI was 32.1 +/- 5.9 kg/m(2). Prevalence of diabetes, dyslipidemia, arterial hypertension, and metabolic syndrome was 68.75%, 82.29%, 63.54% and 81.05%, respectively. Patients with cIV above 30 ng/mL had a 5.57-times (IC: 1.86-16.69) the chance of having significant fibrosis and 7.61-times (IC: 2.27-25.54) the chance of having advanced fibrosis versus patients with values below 30 ng/mL. HA, PC III, LN and CG did not detect the presence of significant and advanced fibrosis. The AUROC of clV for detection of significant (0.718) and advanced fibrosis (0.791) was better than that of other serum biomarkers. Conclusion: Type 4 collagen could predict the presence of significant and advanced fibrosis in NAFLD patients and it would be a useful tool in routine clinical practice. (C) 2020 Fundacion Clinica Medica Sur, A.C.
  • 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.
  • article 8 Citação(ões) na Scopus
    High Prevalence of Hepatitis B Subgenotype D4 in Northeast Brazil: an Ancient Relic from African Continent?
    (2018) CRUZ-SANTOS, Max D.; GOMES-GOUVEA, Michele S.; COSTA-NUNES, Jomar D.; MALTA-ROMANO, Camila; TELES-SOUSA, Marinilde; FONSECA-BARROS, Lena M.; CARRILHO, Flair J.; PAIVA-FERREIRA, Adalgisa de S.; REBELLO-PINHO, Joao R.
    Introduction. Hepatitis B virus (HBV) infection leads to a chronic liver disease that is distributed worldwide. The characterization of HBV into genotypes/subgenotypes is not only a mere procedure for distinguishing different HBV strains around the world because determining their geographic distribution is crucial to understanding their spread across the world. Material and methods. We characterized different HBV genotypes and subgenotypes in five municipalities located in northeastern Maranhao, in the Brazilian north Atlantic coast. 92 HBsAg-positive individuals were submitted to PCR (polymerase chain reaction). Fifty samples were sequenced using automated Sanger sequencing and classified by phylogenetic methods. Results. Subgenotypes D4 and A1 were found in 42 (84%) and eight (16%) samples, respectively. To our knowledge, this is the first study to describe a high frequency of subgenotype D4 in any population. Subgenotype A1 is frequently found across Brazil, but D4 has been rarely detected and only in a few Brazilian states. This study shows the characterization of HBV subgenotypes from a population based study in the state of Maranhao, particularly in populations that do not have frequent contact with populations from other regions of the world. Conclusion. Our findings showed a HBV subgenotype profile that probably reflect the viruses that were brought with the slave trade from Africa to Maranhao. This study also reinforces the need to evaluate the status of HBV dispersion not only in large urban centers, but also in the hinterland, to enable the implementation of effective control and treatment measures.
  • article 5 Citação(ões) na Scopus
    Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study
    (2021) CHAGAS, Aline Lopes; MATTOS, Angelo A.; DINIZ, Marcio A.; FELGA, Guilherme E. G.; BOIN, Ilka F. S. F.; SILVA, Rita C. M. A.; SILVA, Renato F.; GARCIA, Jose H. P.; LIMA, Agnaldo S.; COELHO, Julio C. U.; BITTENCOURT, Paulo L.; ALVES, Venancio A. F.; D'ALBUQUERQUE, Luiz Augusto Carneiro; CARRILHO, Flair J.
    Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called Brazilian Milan Criteria(BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. Materials and Methods: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. Results: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. Conclusions: In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used. (C) 2020 Fundacion Clinica Medica Sur, A.C.