Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis

Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors. Patients and methods: This was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%. Results: 441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p = 0.007) and level of hemoglobin (p = 0.023). Conclusion: Thrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels

Transient hepatic elastography has the best performance to evaluate liver fibrosis in non-alcoholic fatty liver disease (NAFLD)

Introduction and aim: The gold-standard for fibrosis diagnosis in non-alcoholic fatty liver disease (NAFLD) is liver biopsy, despite its invasive approach, sampling limitations and variability among observers. The objective was to validate the performance of non-invasive methods (Fibroscan™; APRI, FIB4 and NAFLD score) comparing with liver biopsy in the evaluation of liver fibrosis in patients with NAFLD. Material and methods: NAFLD patients ≥18 years of age who were submitted to liver biopsy were included and evaluated at two reference tertiary hospitals in Brazil with transient hepatic elastography (THE) assessment through Fibroscan™, APRI, FIB4 and NAFLD scores were determined. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for the diagnosis of advanced fibrosis were calculated to evaluate the performance of these non-invasive methods in NAFLD patients, adopting liver biopsy as the gold standard. Results: A total of 104 patients were studied. At three different cutoff values (7.9, 8.7 and 9.6 kPa) THE presented the highest sensitivity values (95%, 90% and 85% respectively), and the highest NPV (98%, 96.4% and 95.1% respectively) for the diagnosis of advanced fibrosis. It also presented the highest AUROC (0.87; CI 95% 0.78–0.97). Conclusion: When compared to the gold standard, transient hepatic elastography presented the best performance for the diagnosis and exclusion of advanced fibrosis in patients with NAFLD, overcoming APRI, FIB4 and NAFLD score

Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline

Submitted by Nuzia Santos ([email protected]) on 2015-03-02T18:59:13Z No. of bitstreams: 1 2014_133.pdf: 1767507 bytes, checksum: 7391488fb6c7b01f4d8694e5da140f58 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-02T18:59:19Z (GMT) No. of bitstreams: 1 2014_133.pdf: 1767507 bytes, checksum: 7391488fb6c7b01f4d8694e5da140f58 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-02T19:12:15Z (GMT) No. of bitstreams: 1 2014_133.pdf: 1767507 bytes, checksum: 7391488fb6c7b01f4d8694e5da140f58 (MD5)Made available in DSpace on 2015-03-02T19:12:15Z (GMT). No. of bitstreams: 1 2014_133.pdf: 1767507 bytes, checksum: 7391488fb6c7b01f4d8694e5da140f58 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro,RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exército. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exército. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Fundação Oswaldo Cruz. Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, Minas Gerais, Brasil.Background: The live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine. Methods: Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees. Results and discussion: The results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10). Conclusions: The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine

Booster dose after 10 years is recommended following 17DD-YF primary vaccination

Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Governo do Estado de Minas Gerais. Secretaria de Estado de Saúde. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Universidade Federal de Alfenas. Alfenas, MG, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Instituto de Biologia do Exercito. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Assessoria Clínica de Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiologicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Assessoria Clínica de Bio-Manguinhos. Rio de Janeiro, RJ, Brasil.Ministerio da Saude. Secretaria de Vigilancia em Saude. Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Brasil.Universidade de Brasília. Brasilia, DF, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.US Food and Drug Administration. Center for Biologics Evaluation and Research. Silver Spring, MD USAFundação Oswaldo Cruz. Diretoria Regional de Brasília. Brasília, DF, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Publica. Rio de Janeiro, DF, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Renê Rachou. Belo Horizonte, MG, Brasil.A single vaccination of Yellow Fever vaccines is believed to confer life-long protection. In this study, results of vaccinees who received a single dose of 17DD-YF immunization followed over 10 y challenge this premise. YF-neutralizing antibodies, subsets of memory T and B cells as well as cytokine-producing lymphocytes were evaluated in groups of adults before (NVday0) and after (PVday30-45, PVyear1-4, PVyear5-9, PVyear10-11, PVyear12-13) 17DD-YF primary vaccination. YF-neutralizing antibodies decrease significantly from PVyear1-4 to PVyear12-13 as compared to PVday30-45, and the seropositivity rates (PRNT≥2.9Log10mIU/mL) become critical (lower than 90%) beyond PVyear5-9. YF-specific memory phenotypes (effector T-cells and classical B-cells) significantly increase at PVday30-45 as compared to na've baseline. Moreover, these phenotypes tend to decrease at PVyear10-11 as compared to PVday30-45. Decreasing levels of TNF-α(+) and IFN-γ(+) produced by CD4(+) and CD8(+) T-cells along with increasing levels of IL-10(+)CD4(+)T-cells were characteristic of anti-YF response over time. Systems biology profiling represented by hierarchic networks revealed that while the na've baseline is characterized by independent micro-nets, primary vaccinees displayed an imbricate network with essential role of central and effector CD8(+) memory T-cell responses. Any putative limitations of this cross-sectional study will certainly be answered by the ongoing longitudinal population-based investigation. Overall, our data support the current Brazilian national immunization policy guidelines that recommend one booster dose 10 y after primary 17DD-YF vaccination

Direct antiviral therapy for treatment of hepatitis C: A real-world study from Brazil

Introduction and objectives: Direct antiviral agents (DAAs) including sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM) and ombitasvir, paritaprevir and dasabuvir were introduced 2015 in Brazil for treatment of hepatitis C virus (HCV) infection. The aims of this study were to assess effectiveness and safety of HCV treatment with DAA in real-life world in a highly admixed population from Brazil. Materials and methods: All Brazilian reference centers for HCV treatment were invited to take part in a web-based registry, prospectively conducted by the Brazilian Society of Hepatology, to assess outcomes of HCV treatment in Brazil with DAAs. Data to be collected included demographics, disease severity and comorbidities, genotype (GT), viral load, DAA regimens, treatment side effects and sustained virological response (SVR). Results: 3939 patients (60% males, mean age 58 ± 10 years) throughout the country were evaluated. Most had advanced fibrosis or cirrhosis, GT1 and were treated with SOF/DCV or SOF/SIM. Overall SVR rates were higher than 95%. Subjects with decompensated cirrhosis, GT2 and GT3 have lower SVR rates of 85%, 90% and 91%, respectively. Cirrhosis and decompensated cirrhosis in GT1 and male sex and decompensated cirrhosis in GT3 were significantly associated with no SVR. Adverse events (AD) and serious AD occurred in 18% and 5% of those subjects, respectively, but less than 1% of patients required treatment discontinuation. Conclusion: SOF-based DAA regimens are effective and safe in the heterogeneous highly admixed Brazilian population and could remain an option for HCV treatment at least in low-income countries