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dc.rights.licenseReconocimiento 4.0 Internacional
dc.contributor.advisorGrillo Ardila, Carlos Fernando
dc.contributor.authorBurgos Cárdenas, Álvaro Javier
dc.date.accessioned2022-02-25T16:24:03Z
dc.date.available2022-02-25T16:24:03Z
dc.date.issued2021
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/81060
dc.descriptionilustraciones, gráficas, tablas
dc.description.abstractEl interferón alfa y los análogos de nucleótidos son los pilares del tratamiento para la Hepatitis B Crónica ; los análogos de nucleótidos son los más usados debido a una menor tasa de eventos adversos, en comparación al Interferón. Sin embargo, no son capaces de eliminar el virus de las células infectadas, la tasa de control serológico es menor y la duración del tratamiento es indefinida. Por lo mencionado, se hace necesarios factores pronósticos para determinar, en la medida de los posible, a los pacientes que tengan mayor chance de responder a la terapia con Interferón. Actualmente, las concentraciones séricas de los antígenos o proteínas virales, tal es como el antígeno de superficie(HBsAg), antígeno e (HBeAg) y la proteína relacionada con el core (HBcrAg), parecen ser factores pronósticos prometedores. Por anterior, se realizó una revisión sistemática con metanálisis para evaluar la asociación entre la concentración del HBsAg, HBeAg y HBcrAg medidos a la semana 12 y una respuesta favorable al terminar tratamiento con interferón . Metodología: Se realizó una búsqueda sistemática de la literatura, en MEDLINE, EMBASE, y CENTRAL de Cochrane, y otras fuentes de información, como páginas de sociedades científicas y revistas relacionadas con el tema; literatura gris y congresos internacionales. Se seleccionaron los artículos que evaluaran la asociación de la concentración sérica de HBsAg, HBeAg y HBcrAg a la semana 12 de tratamiento con interferón y la respuesta al final del tratamiento. Los factores pronósticos, en este caso las concentraciones de los antígeno virales, fueron dicotomizados para el análisis de la siguiente manera: se considero como presente el factor pronóstico cuando un individuo tenia concentraciones de estas partículas a la semana 12 por debajo de un punto de corte establecido, de la misma manera, el factor se encontraba presente cuando el delta de la concentración del antígeno, entre la semana 0 y la semana 12 de tratamiento, se encontraba por encima de un umbral establecido por los autores del estudio. Dichos puntos de corte o umbrales fueron determinadas por los autores de cada estudio y se determino su asociación con la respuesta al tratamiento, de acuerdo con la frecuencia de respuesta serológica, viral o combinadas obtenidas entre los individuos con y sin el factor pronóstico, al menos al término del tratamiento. Resultados: 31(5.167 participantes) estudios cumplieron los criterios de inclusión. La certeza de la evidencia sobre la concentración del HBsAg a la semana 12 como factor pronóstico fue calificada como de muy baja calidad, de acuerdo a la metodología GRADE por lo que existe incertidumbre sobre si existe asociación entre el factor y el desenlace, sea que se analice como una concentración absoluta por debajo de un punto de corte o el delta entre la semana 0 y 12 (Delta para eliminación del HBsAg: OR: 6.02, IC95%: 3.76-9.65 tau2: 0 I2. 0.0%| Concentración absoluta eliminación del HBsAg: OR: 5.490, IC95%: 2.7925-10.793 tau2: 0 I2. 0.0% ) (Delta para la seroconversión del HBeAg: OR: 5.39 IC95%:2.55-11.41| Concentración absoluta para la seroconversión del HBeAg: OR 3.12 IC95%: 2.15-4.52, tau2:0.116, I2: 47% ). Con respecto a la evaluación como factor pronóstico de la concentración del HBeAg medido a la semana 12 de tratamiento con interferón, se encontró que la certeza de la evidencia era de muy baja calidad, por lo que se determino que existe incertidumbre en cuanto a si tener una disminución entre la semana 0 y 12 por encima de un umbral establecido o una concentración por debajo del punto de corte del HBeAg, se asocien con una mayor posibilidad del obtener la eliminación del HBsAg o seroconversión del HBeAg al menos al terminar el tratamiento (Delta para eliminación del HBsAg OR:7.27 IC95%:2.0-26.411|Concentración absoluta para seroconversión del HBeAg: OR ajustado(carga viral, ALT, edad): 10.89 IC95% : 2.63-45.17 ). Para el HBcrAg, con evidencia de muy baja calidad, no se puede determinar si la disminución de este antígeno entre la semana 0 y 12 no se asocia con la eliminación del HBsAg (OR: 2.76 IC95%: 0.85-8.9). En relación con los desenlaces secundarios, con muy baja calidad de la evidencia, no se puede establecer si la disminución entre la semana 0 y 12 o una concentración por debajo del punto de corte de los tres factores pronósticos, se asoció con una respuesta viral o combinada. Conclusiones: Los resultados de esta revisión muestran que no existe certeza sobre la asociación entre los factores pronósticos aquí estudiados y la respuesta al tratamiento ya que la evidencia fue de muy baja calidad y no se puede concluir que en pacientes con Hepatitis b Crónica tratados con Interferón alfa, la medición en sangre de la concentración del HBsAg a la semana 12 después de iniciado el tratamiento, pueda predecir la respuesta al tratamiento, cuando esta respuesta es medida como serológica, viral o combinada. Para mejorar la calidad de la evidencia, hacen falta ensayos clínicos en los que se asigne aleatoriamente a los participantes en función del factor pronósticos a modificar el tratamiento o continuar con el. Asimismo, se podrían realizar mejores análisis multivariados o estudios pronósticos en los que haya mejor control de la confusión. (Texto tomado de la fuente).
dc.description.abstractAlpha interferon and nucleotide analogs are the mainstays of treatment for Chronic Hepatitis B; Nucleotide analogs are the most used due to a lower rate of adverse events than interferon. However, they cannot eliminate the virus from infected cells, their serological control rate is lower than interferon, and the duration of treatment is indefinite. Due to the above, prognostic factors are necessary to determine, as far as possible, the patients who are most likely to respond to Interferon therapy. Currently, serum concentrations of viral proteins or ends, such as surface end (HBsAg), e-end (HBeAg), and core-associated protein (HBcrAg), appear to be promising prognostic factors. Previously, a systematic review with meta-analysis was performed to assess the association between HBsAg, HBeAg, and HBcrAg concentration measured at week 12 and a favorable response at the end of interferon treatment. Methodology: We performed a systematic search of the literature in MEDLINE, EMBASE, and Cochrane CENTRAL, and other sources of information, such as pages of scientific societies and journals related to the subject, like gray literature and international conferences. We selected articles that evaluated the association of the serum concentration of HBsAg, HBeAg, and HBcrAg at week 12 of treatment with interferon and the response at the end of treatment. The prognostic factors, in this case, the concentrations of viral antigens, were dichotomized for the analysis as follows: we considered the prognostic factor present when an individual had concentrations of these particles at week 12 below a cut-off point. In the same way, the factor was present when the delta of the antigen concentration, between week 0 and week 12 of treatment, was above a threshold established by the study authors. The authors of each study determined these cut-off points or thresholds, and we established their association with the response to treatment according to the frequency of serological, viral, or combined response obtained between individuals with and without the prognostic factor, at least at the end of treatment. Results: 31 (5,167 participants) studies met the inclusion criteria. We classified the certainty of the evidence on the concentration of HBsAg at week 12 as a prognostic factor as very low quality, according to the GRADE methodology. For that reason, we considered there is uncertainty about an association between the factor and the outcome, it does not matter how is analyzed as an absolute concentration below a cut-off point or the delta between week 0 and 12 (Delta for HBsAg clearance: OR: 6.02, 95% CI: 3.76-9.65 tau2: 0 I2. 0.0%| Absolute concentration clearance of HBsAg: OR: 5.490, 95% CI: 2.7925-10.793 tau2: 0 I2. 0.0% ) (Delta for HBeAg seroconversion: OR: 5.39 95% CI: 2.55-11.41 | Absolute concentration for HBeAg seroconversion: OR 3.12 95% CI : 2.15-4.52, tau2:0.116, I2: 47% ). Regarding the evaluation as a prognostic factor of the concentration of HBeAg measured at week 12 of treatment with interferon, we found that the certainty of the evidence was of very low quality. Therefore, we determined that there is uncertainty as to whether having a decrease between week 0 and 12 above an established threshold or a concentration below the cut-off point of HBeAg are associated with a greater possibility of obtaining the elimination of HBsAg or seroconversion of HBeAg at least at the end of treatment (Delta for HBsAg clearance OR: 7.27 95% CI: 2.0-26.411 | Absolute concentration for HBeAg seroconversion: adjusted OR (viral load, ALT, age): 10.89 95% CI: 2.63-45.17 ). For HBcrAg, with very low-quality evidence, it cannot be determined whether the decrease in this antigen between weeks 0 and 12 are not associated with the elimination of HBsAg (OR: 2.76 95% CI: 0.85-8.9). Concerning the secondary outcomes, with very low quality of evidence, it cannot be established whether the decrease between weeks 0 and 12 or a concentration below the cut-off point of the three prognostic factors was associated with a viral response or combined. Conclusions: The results of this review show that there is no certainty about the association between the prognostic factors studied here and the response to treatment since the evidence was of very low quality and we cannot concluded that in patients with Chronic Hepatitis B treated with Interferon alfa, the measurement in the blood of the HBsAg concentration at week 12 after starting treatment, can predict the response to treatment when this response is measured as serological, viral or combined. To improve the quality of the evidence, we propose clinical trials in which participants are randomly assigned based on the prognostic factor to modify the treatment or continue with it. Likewise, better multivariate analyses or prognostic studies could be carried out to control confusion better.
dc.format.extentxx, 137 páginas
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.publisherUniversidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc610 - Medicina y salud
dc.titleEvaluación de los antígenos virales como factores pronósticos de respuesta al tratamiento con interferón alfa en pacientes con Hepatitis B Crónica: Revisión sistemática y meta análisis
dc.typeTrabajo de grado - Maestría
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.publisher.programBogotá - Medicina - Maestría en Epidemiología Clínica
dc.description.notesIncluye anexos
dc.description.degreelevelMaestría
dc.description.degreenameMagíster en Ciencias Epidemiología Clínica
dc.identifier.instnameUniversidad Nacional de Colombia
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourlhttps://repositorio.unal.edu.co/
dc.publisher.facultyFacultad de Medicina
dc.publisher.placeBogotá, Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
dc.relation.indexedBireme
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.decsInterferon-alpha
dc.subject.decsInterferón-alfa
dc.subject.decsHepatitis B
dc.subject.decsHepatitis B
dc.subject.decsAntígenos
dc.subject.decsAntigens
dc.subject.proposalHepatitis B Crónica
dc.subject.proposalPronóstico
dc.subject.proposalInterferón
dc.subject.proposalChronic Hepatitis B
dc.subject.proposalPrognosis
dc.subject.proposalInterferon
dc.subject.proposalChronic Hepatitis B
dc.subject.proposalPrognosis
dc.subject.proposalInterferon
dc.title.translatedEvaluation of viral antigens as prognostic factors of response to treatment with interferon alpha in patients with Chronic Hepatitis B: Systematic review and meta-analysis
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2
dcterms.audience.professionaldevelopmentPúblico general


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Reconocimiento 4.0 InternacionalThis work is licensed under a Creative Commons Reconocimiento-NoComercial 4.0.This document has been deposited by the author (s) under the following certificate of deposit