FLAIR JOSE CARRILHO
Projetos de Pesquisa
Unidades Organizacionais
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
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
3 resultados
Resultados de Busca
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- HCV Viremia Drives an Increment of CD86 Expression by Myeloid Dendritic Cells(2013) MALTA, F. M.; BRUNO, F. R.; CARVALHO, K. I.; NASTRI, A. C. S. S.; KALIL, J.; CARRILHO, F. J.; KALLAS, E. G.; PINHO, J. R. R.The host immune response, including innate and adaptive immunity, plays a critical role in determining the outcome of viral infection. Nevertheless, little is known about the exact reasons for the failure of the host immune system in controlling hepatitis C virus (HCV) infection. Impairment of dendritic cells (DCs) function is probably one of the mechanisms responsible for immune evasion of HCV. In this study, the frequency and phenotype of DCs subsets were analyzed in three groups: HCV-infected individuals who developed viral persistence (1), HCV-infected individuals who spontaneously cleared the virus (2) and HCV-seronegative uninfected subjects (3). The results showed that the frequency of DCs subsets was not statistically significant between groups. Plasmacytoid DCs circulating exhibited an immature phenotype characterized by low expression of CD86. On the other hand, CD86 expression in myeloid DCs was significantly higher in chronic infected individuals compared to healthy controls (P=0.037). A positive correlation was observed between CD86(+) myeloid DC (mDC) and HCV viral load (r=0.4121, P=0.0263). These results suggest that HCV did not have an inhibitory effect on mDC maturation and the HCV viremia drives the increase of CD86 expression in mDC. The regulation of DCs maturation and migration lies at the level of intracellular signaling. HCV can activate or block intracellular signaling pathways and alter DC function. In conclusion, the present study suggests that imbalance of DC maturation by the virus represents a mechanism of evasion of the immune system despite the fact that HCV viremia appears to exert a stimulatory effect on cell-surface immune phenotype. J Med. Virol. 85:1919-1924, 2013. (c) 2013 Wiley Periodicals, Inc.
- The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank(2013) ALVES, R.; QUEIROZ, A. T. L.; PESSOA, M. G.; SILVA, E. F. da; MAZO, D. F. C.; CARRILHO, F. J.; CARVALHO-FILHO, R. J.; CARVALHO, I. M. V. G. deSeveral new direct-acting antiviral (DAA) drugs are in development for chronic hepatitis C viral (HCV) infection, and NS3-NS4A serine protease and the NS5B RNA-dependent RNA polymerase have been the major targets. HCV variants displaying drug-resistant phenotypes have been observed both in vitro and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (NS3) and polymerase (NS5B) regions from treatment-naive HCV patients infected with genotypes 1a, 1b and 3a. All 1383 NS3 protease sequences (genotype 1a=680, 1b=498 and 3a=205) and 806 NS5B polymerase sequences (genotypes 1a=471, 1b=329, 3a=6) were collected from Los Alamos databank. Genotype 3a protease sequences showed the typical low-level resistance mutation V36L. NS3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the NS5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre-existence of HCV variants resistant to first-generation protease inhibitors and to non-nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre-existing mutations associated with resistance to Palm II and Thumb I polymerase inhibitors, respectively.
- Clinical and epidemiological aspects of hepatocellular carcinoma in Brazil(2013) KIKUCHI, Luciana; CHAGAS, Aline L.; ALENCAR, Regiane S. S. M.; PARANAGUA-VEZOZZO, Denise C.; CARRILHO, Flair J.The global hepatocellular carcinoma (HCC) incidence is widely variable, depending on geographic region and the prevalence of major risk factors. In Brazil, two large multicentre retrospective studies were performed to investigate clinical and epidemiological aspects of HCC. In the first study, performed in 1997, HCC was found in cirrhotic livers in 71% of cases. Chronic alcoholism was present in 36% of cases, chronic hepatitis B in 35% and hepatitis C in 25%. In a 2010 survey, cirrhosis was present in 98% of cases and HCV was the main aetiology (54%). Differences in HBV prevalence were found among regions. Selection of HCC treatment depends on tumour burden, liver function and performance status. Liver transplantation ( LT) is the best available curative treatment for HCC in its early stage and with compromised liver function. After modifications in priority policy, the number of patients with early HCC submitted for LT has increased in the past 5 years in Brazil. Chemoembolization is the most common initial HCC therapy in early and intermediate stages of HCC in Brazil.