CARLOS EDUARDO DE MELO
Projetos de Pesquisa
Unidades Organizacionais
LIM/47 - Laboratório de Hepatologia por Vírus, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients(2011) ARAUJO, E. S. A.; DAHARI, H.; NEUMANN, A. U.; CAVALHEIRO, N. de Paula; MELO, C. E.; MELO, E. S. de; LAYDEN, T. J.; COTLER, S. J.; BARONE, A. A.The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 mu g/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 +/- 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline < 1.19 log for genotype-1 and < 0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) < 0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (< 0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.
- Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation(2015) SONG, Alice Tung Wan; MELLO, Evandro Sobroza de; ALVES, Venancio Avancini Ferreira; CAVALHEIRO, Norma de Paula; MELO, Carlos Eduardo; BONAZZI, Patricia Rodrigues; TENGAN, Fatima Mitiko; FREIRE, Maristela Pinheiro; BARONE, Antonio Alci; D'ALBUQUERQUE, Luiz Augusto Carneiro; ABDALA, EdsonHistology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.
conferenceObject Serial dilution of semen samples and better results in HCV-PCR in patients with hepatitis C infection(2012) CAVALHEIRO, N.; SANTOS, A.; MELO, C.; TENGAN, F.; LEVI, J.- Pharmacodynamics of PEG-IFN-alpha-2a and HCV Response as a Function of IL28B Polymorphism in HIV/HCV-Coinfected Patients(2011) ARAUJO, Evaldo Stanislau Affonso de; DAHARI, Harel; COTLER, Scott J.; LAYDEN, Thomas J.; NEUMANN, Avidan U.; MELO, Carlos Eduardo; BARONE, Antonio AlciWe examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P <= 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, delta, were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.
conferenceObject Lack of association between SOCS3 rs4969170 and interleukin 28B genes with therapeutic response in Brazilian HCV carriers treated with PEG-IFN/RBV(2012) MELO, Carlos E.; ARAUJO, Evaldo S.; MANCHIERO, Caroline; MARTINS, Luciane P.; TENGAN, Fatima M.; BARONE, Antonio A.Chronic HCV infections are related with the production of inappropriate cytokine levels in inflammatory and immune response. IFN-α must activate a signal transduction cascade that involves different intracellular proteins driving interferon-inducible genes to be activated. The proteins suppressor of cytokine signaling (SOCS) represents the main cellular mechanism for cytokine (such as IL10 and IFN) negative regulation. Immune responses may be associated with SOCS3 production driven by therapy against HCV and it seems to be regulated by single nucleotide polymorphisms (SNPs) within SOCS3 gene. Recently, genome-wide association studies have linked response to PEG-IFN/RBV therapy with SNPs near the IL28B gene (rs12979860), encoding for interferon-lambda-3 (IL28B). The rs12979860 CC genotype is associated with a greater rate of sustained virological response (SVR) than the CT or TT genotypes in different HCV patients populations. In this study, we evaluated the frequencies of SOCS3 and IL28B polymorphisms genes and their association with the response to IFN based antiviral therapy in chronic hepatitis C infection. After IRB ethics approval, frozen samples from 142 HCV Genotype-1 infected Brazilian patients were analyzed. Genomic DNA from patients classified as responders (R=71) and nonresponders (NR=71) to a PEG-IFN/RBV therapy were used in this study. The SNPs near the IL28B (rs12979860) and SOCS3 (rs4969170) genes were examined using an assay with allele specific PCR probes. According recent publications, IL28B CC genotype was considered the more favorable profile to reach Sustained Virologic Response (SVR). Regarding SOCS3 AA genotype was also recently strongly associated with failure of the IFN-α based therapy. The results are summarized in the table 1. As expected IL28B CC SNP was associated with a better response to antiviral therapy. Conversely, we could not observe a clear association between the polymorphism rs4969170 SOCS3 gene and lack of response to IFN based therapy in our population. Therefore we conclude that the SOCS3 rs4969170 was not as good as IL28B on predicting therapy outcome for HCV.