Efectividad de los antivirales de acción directa de segunda generación en el tratamiento de la hepatitis C crónica / Effectiveness of second-generation direct-acting antivirals in chronic hepatitis C

Fundamento: Los antivirales de acción directa de segunda generación (AAD) han demostrado porcentajes elevados de respuesta viral sostenida (RVS) en el tratamiento de la hepatitis C crónica en ensayos clínicos. Este estudio tiene como objetivo estimar la efectividad de los AAD en el tratamiento de esta enfermedad. Material y métodos: Se estudiaron pacientes monoinfectados por el virus de la hepatitis C (VHC) y coinfectados por VHC y virus de la inmunodeficiencia humana (VIH) que iniciaron tratamientos libres de interferón con AAD durante 2015. La RVS se definió como una carga viral indetectable a las 12 semanas de finalizar el tratamiento, y fue el indicador principal de efectividad. Resultados: Se incluyeron 293 pacientes, 52 (17,7%) coinfectados por VIH. Los genotipos VHC más prevalentes fueron el 1b en monoinfectados (41,5%) y 1a en coinfectados (40,4%). La proporción de cirróticos fue superior en la población coinfectada (69,2% vs 41,1%; p<0,0001), en su mayoría Child-Pugh A. La cifra global de RVS fue del 96,9% (284/293) en un análisis por intención de tratar (IC 95%: 94,9-98,9%), siendo 4 los pacientes con fracaso virológico. Tanto pacientes naïve como pretratados tuvieron RVS superior al 95%, y en la mayoría de subgrupos establecidos según la presencia o no de cirrosis, la coinfección VIH y el genotipo, la efectividad se situó próxima o por encima del 90%. Conclusiones: Los AAD presentan una efectividad elevada, igual o superior a la descrita en los ensayos clínicos, e incluso en subpoblaciones difíciles de tratar (AU)

Background: Second-generation direct-acting antivirals (DAA) have shown high sustained virologic response (SVR) for the treatment of chronic hepatitis C in clinical trials. The objective of this study is to estimate DAA effectiveness in treatment of this disease. Methods: Hepatitis C virus (HCV) monoinfected patients and HCV-human immunodeficiency virus (HIV) coinfected patients who started interferon-free DAA based regimens during 2015 were included. The primary effectiveness outcome was SVR, defined as an undetectable viral load 12 weeks after the end of treatment. Results: A total of 293 patients were enrolled, and 52 (17.7%) were HIV coinfected. HCV 1b genotype was the most prevalent in monoinfected patients (41.5%) and 1a in HIV coinfected patients (40.4%). The proportion of cirrhosis was higher among HIV coinfected patients (69.2% vs 41.1%; p<0.0001), mostly Child-Pugh A. SVR was achieved by 96.9% of patients (284/293), in an intention-to-treat analysis (CI 95%: 94.9- 98.9), in which just 4 people had virologic failure. Both naïve and pretreated patients had SVR higher than 95%, and in most of subgroups, according to the presence of cirrhosis, HIV coinfection and HVC genotype, effectiveness rates were near or above 90%. Conclusions: DAA are highly effective, with similar or higher rates of SVR than that found in clinical trials, and even among difficult to treat populations (AU)

[Influence of the -866G/A polymorphism of the UCP2 gene on an obese pediatric population]. / Influencia del polimorfismo -866G/A del gen de la UCP2 en población infantil obesa.

OBJECTIVE: In the present study, our objectives were to evaluate the prevalence of -866G/A mutation of UCP2 gene and to study its influence on the phenotype of obese children (11-12 years old) from Navarra. BACKGROUND AND STUDY SETTING: Obesity is a disease with a multifactorial origin that may related be to the presence of mutations and polymorphisms in several candidate genes. The gene of the uncoupling protein UCP2 is one of the most studied ones in relation to obesity because it seems to participate in body composition and several metabolic processes control. Three polymorphisms have been described for this gene: an insertion/deletion of 45 nucleotides, a nucleotide change of guanine for adenine in -866 position, an another change that replaces alanine for valine at amino acid position 55. According to several studies, the -866G allele is related to an increased risk of developing obesity, although the results are contradictory about this association in the literature. SUBJECTS: The study was carried out on 125 obese children (52% male), aged 11-12 years, selected through the Pediatric Endocrinology Departments of Clínica Universitaria and Hospital Virgen del Camino of Pamplona (Spain), the reported results on this association are contradictory. INTERVENTIONS: After checking the inclusion criteria, anthropometrical data (weight, height, BMI, tricipital and subscapular skinfolds) were taken, and the percentage of fat mass was measured by bioelectrical impedance. Besides, plasma levels of total cholesterol, glucose, insulin, and leptin were measured. DNA was extracted from white blood cells to determine the genotype by PCR technique followed by BstUI digestion and further visualization in agarose gel with 2% ethidium bromide. RESULTS: The genetic analysis revealed a 0.404 frequency of the allele A, with a percentage of individuals G/G, G/A, and A/A of 40.0%, 39.2%, and 20.8%, respectively. Carriers of the A allele had a significantly higher sum of tricipital and subscapular folds (p = 0.034). No significant differences between mutant and non-mutant subjects with regard to the studied biochemical variables were observed. CONCLUSIONS: Subjects carrying the polymorphism present higher values of tricipital and subscapular skinfolds as compared to non-mutant subjects, which may indicate a relationship between the presence of the A allele in obese children and higher amounts of subcutaneous fat.

Influencia del polimorfismo -866 G/A del gen de la UCP2 en población infantil obesa / Influence of the -866g/a polymorphism of the ucp2 gene on an obese pediatric population

OBJETIVO: En el presente estudio se pretende evaluar la prevalencia de la mutación -866 G/A del gen de la UCP2 y conocer su influencia sobre el fenotipo de los niños (11- 12 años) navarros obesos. ANTECEDENTES Y ÁMBITO DEL ESTUDIO: La obesidad es una enfermedad de origen multifactorial, que puede estar relacionada con la presencia de mutaciones y polimorfismos en diversos genes candidatos. El gen de la proteína desacoplante UCP2 es uno de los más estudiados en relación con la obesidad porque parece participar en el control de la composición corporal y de diversos procesos metabólicos. Se han descrito tres polimorfismos en este gen: una inserción/deleción de 45 nucleótidos, un cambio del nucleótido guanina por adenina en la posición -866 y otro que origina un reemplazo de alanina por valina en el aminoácido 55. Según diferentes estudios, el alelo - 866G está relacionado con un mayor riesgo de desarrollar obesidad, aunque en la literatura aparecen resultados contradictorios en cuanto a esta asociación. SUJETOS: El estudio se llevó a cabo en 125 niños (52% varones) obesos de 11-12 años de edad, seleccionados a través de los Servicios de Endocrinología Pediátrica de la Clínica Universitaria y del Hospital Virgen del Camino (Pamplona), obteniendo el consentimiento informado de acuerdo con la declaración de Helsinki. INTERVENCIONES: Tras verificar el cumplimiento de los criterios de inclusión se tomaron medidas antropométricas (peso, talla, IMC, pliegue tricipital y subescapular) y se determinó el porcentaje de masa grasa por medio de impedancia bioeléctrica. Además se midieron los niveles plasmáticos de colesterol total, glucosa, insulina y leptina. Se procedió también a la extracción del ADN de las células sanguíneas de la serie blanca para determinar el genotipo mediante la técnica de PCR seguida de una digestión con BstUI y posterior visualización en un gel de agarosa con un 2% de bromuro de etidio. RESULTADOS: El análisis genético reveló una frecuencia del alelo A de 0,404, con un porcentaje de individuos G/G, G/A, y A/A del 40,0%, 39,2% y 20,8%, respectivamente. Los portadores del alelo A presentaron un valor significativamente mayor de la suma de los pliegues tricipital y subescapular (p=0,034). No se observaron diferencias significativas entre los sujetos mutados y los no mutados en cuanto a las variables bioquímicas estudiadas. CONCLUSIONES: Los sujetos portadores del polimorfismo presentan valores más altos para los pliegues tricipital y subescapular frente a los no mutados lo que podría indicar una relación entre la presencia del alelo A en niños obesos y niveles mayores de grasa subcutánea (AU)

OBJECTIVE: In the present study, our objectives were to evaluate the prevalence of -866G/A mutation of UCP2 gene and to study its influence on the phenotype of obese children (11-12 years old) from Navarra. BACKGROUND AND STUDY SETTING: Obesity is a disease with a multifactorial origin that may related be to the presence of mutations and polymorphisms in several candidate genes. The gene of the uncoupling protein UCP2 is one of the most studied ones in relation to obesity because it seems to participate in body composition and several metabolic processes control. Three polymorphisms have been described for this gene: an insertion/ deletion of 45 nucleotides, a nucleotide change of guanine for adenine in -866 position, an another change that replaces alanine for valine at amino acid position 55. According to several studies, the -866G allele is related to an increased risk of developing obesity, although the results are contradictory about this association in the literature. SUBJECTS: The study was carried out on 125 obese children (52% male), aged 11-12 years, selected through the Pediatric Endocrinology Departments of Clínica Universitaria and Hospital Virgen del Camino of Pamplona (Spain), the reported results on this association are contradictory. INTERVENTIONS: After checking the inclusion criteria, anthropometrical data (weight, height, BMI, tricipitaland subscapular skinfolds) were taken, and the percentage of fat mass was measured by bioelectrical impedance. Besides, plasma levels of total cholesterol, glucose, insulin,and leptin were measured. DNA was extracted from white blood cells to determine the genotype by PCR technique followed by BstUI digestion and furthervisualization in agarose gel with 2% ethidium bromide. RESULTS: The genetic analysis revealed a 0.404 frequency of the allele A, with a percentage of individuals G/G, G/A, and A/A of 40.0%, 39.2%, and 20.8%, respectively. Carriers of the A allele had a significantly higher sum of tricipital and subscapular folds (p = 0.034). No significant differences between mutant and non-mutant subjects with regard to the studied biochemical variables were observed. CONCLUSIONS: Subjects carrying the polymorphism present higher values of tricipital and subscapular skinfolds as compared to non-mutant subjects, which may indicate a relationship between the presence of the A allele in obese children and higher amounts of subcutaneous fat (AU)