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2.
Eur J Gastroenterol Hepatol ; 29(7): 754-758, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28234637

RESUMEN

Background NS3 protease inhibitors (PIs) were the first direct antiviral agents used for the treatment of hepatitis C virus. The combination of second-wave PIs with other direct antiviral agents enabled the use of interferon-free regimens for chronic kidney disease patients on dialysis and renal transplant (RTx) recipients, populations in which the use of interferon and ribavirin is limited. However, the occurrence of PI resistance-associated variants (RAVs), both baseline and induced by therapy, has resulted in the failure of many treatment strategies. Methods The aim of this study was to estimate the prevalence of PI RAVs and of the Q80K polymorphism in chronic kidney disease patients on hemodialysis and RTx recipients. Direct sequencing of the NS3 protease was performed in 67 patients (32 hemodialysis and 35 RTx).Results RAVs to PIs were detected in 18% of the patients: V55A (9%), V36L (1.5%), T54S (1.5%), S122N (1.5%), I170L (1.5%), and M175L (1.5%). Only 1.5% of the patients carried the Q80K polymorphism. The frequency of these mutations was more than two times higher in patients infected with GT1a (25%) than GT1b (9.7%) (P=0.1). The mutations were detected in 20% of treatment-naive patients and in 15.6% of peginterferon/ribavirin-experienced patients (P=0.64). Furthermore, no mutation that would confer high resistance to PIs was detected.Conclusion The Q80K polymorphism was rare in the population studied. The occurrence of RAVs was common, with predominance in GT1a. However, the variants observed were those associated with a low level of resistance to PIs, facilitating the use of these drugs in this special group of patients.


Asunto(s)
Antivirales/uso terapéutico , Farmacorresistencia Viral/genética , Hepacivirus/genética , Hepatitis C/epidemiología , Trasplante de Riñón , Polimorfismo Genético , Inhibidores de Proteasas/uso terapéutico , Diálisis Renal , Insuficiencia Renal Crónica/terapia , Proteínas no Estructurales Virales/genética , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Brasil/epidemiología , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/enzimología , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Fenotipo , Prevalencia , Inhibidores de Proteasas/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo , Adulto Joven
3.
Med Microbiol Immunol ; 205(2): 111-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26272127

RESUMEN

Hepatitis C virus (HCV) infection affects approximately 3 % of the world population. HCV targets hepatic tissue, and most infected patients develop a chronic infection. Currently, studies have demonstrated an association between HCV-RNA replication and miR-122, the most abundant microRNA in the liver. Our aim was to evaluate liver and serum expression of miR-122 in patients infected with HCV genotypes 1 and 3, and to identify possible associations between miR-122 expression and lipid profiles, HCV viral load, apolipoproteins and liver enzymes. MicroRNAs were isolated from blood and liver tissue, and miR-122 expression was quantified by real-time PCR. HCV viral load was quantified by real-time PCR and HCV genotype, and serum biomarkers were obtained from medical report. The levels of miR-122 were higher in liver than those in blood from individuals infected with HCV genotypes 1 and 3 (p < 0.0001). The tissue levels of miR-122 were higher in subjects infected with HCV genotype 3 (6.22-fold, p < 0.001). A positive correlation was observed between the blood and hepatic levels of miR-122 in patients infected with HCV genotype 1 (r = 0.302, p = 0.026); in these patients, an inverse correlation was observed between serum apolipoprotein A-II (ApoA-II) levels and the blood (r = -0.330; p = 0.014) and hepatic (r = -0.311; p = 0.020) levels of miR-122. In patients infected with HCV genotype 3, there was a positive correlation between the hepatic miR-122 and the high-density lipoprotein-HDL (r = 0.412, p = 0.036) and insulin (r = 0.478, p = 0.044). Lipid metabolism proteins and miR-122 expression levels have different relations in HCV-3- and HCV-1-infected patients.


Asunto(s)
Regulación de la Expresión Génica , Genotipo , Hepacivirus/genética , Hepatitis C/genética , Hepatitis C/virología , Hígado/metabolismo , Hígado/virología , MicroARNs/genética , Adulto , Biomarcadores , Biopsia , Femenino , Hepatitis C/metabolismo , Hepatitis C Crónica/genética , Hepatitis C Crónica/metabolismo , Hepatitis C Crónica/virología , Humanos , Metabolismo de los Lípidos , Hígado/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Pruebas de Función Hepática , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Carga Viral
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