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Resúmenes Epistemonikos
Medwave 2014 Sep;14(8):e6019 doi: 10.5867/medwave.2014.08.6019
¿Es efectivo el ácido ursodeoxicólico en cirrosis biliar primaria?
Is ursodeoxycholic acid effective in primary biliary cirrhosis?
Gabriel Rada, Macarena Mac-Namara
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Resumen

El ácido ursodeoxicólico es considerado como terapia de primera línea en pacientes con cirrosis biliar primaria. Su mecanismo en esta patología no está claro y existe controversia sobre su impacto clínico. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 19 bases de datos, identificamos cuatro revisiones sistemáticas que en conjunto incluyen 16 estudios. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el ácido ursodeoxicólico podría no tener ningún efecto sobre el prurito, y que existe incertidumbre sobre su efecto sobre mortalidad, necesidad de trasplante o cualquier otro desenlace importante para el paciente.


 
Problema

La cirrosis biliar primaria es una enfermedad autoinmune con daño de los conductos biliares que produce colestasia y que a largo plazo puede llevar a cirrosis hepática. El ácido ursodeoxicólico es considerado un pilar fundamental del tratamiento, ya que mejora algunos parámetros bioquímicos y posiblemente histológicos. Su impacto sobre desenlaces importantes para el paciente, como mortalidad, necesidad de trasplante, síntomas o calidad de vida no está claro. Presenta efectos adversos frecuentes, principalmente cefalea, mareos y síntomas gastrointestinales como náuseas, vómitos, constipación o diarrea. Tiene un alto costo y en Chile no tiene cobertura por el sistema de salud público.

Métodos

Utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 19 bases de datos, para identificar revisiones sistemáticas y sus estudios primarios incluidos. Con esta información generamos un resumen estructurado, siguiendo un formato preestablecido, que incluye mensajes clave, un resumen del conjunto de evidencia (presentado como matriz de evidencia en Epistemonikos), metanálisis del total de los estudios, tablas de resumen de resultados con el método GRADE, y tabla de otras consideraciones para la toma de decisión.

Mensajes clave

  • El ácido ursodeoxicólico podría no disminuir el prurito en pacientes con cirrosis biliar primaria, y existe incertidumbre sobre si disminuye la mortalidad, la necesidad de trasplante o la morbilidad asociada al daño hepático crónico, porque la calidad de la evidencia es muy baja.
  • Nuestro resumen difiere de las principales guías de práctica clínica, que lo recomiendan fuertemente.
  • Prácticamente no existe investigación en curso que pueda aclarar el rol del ácido ursodeoxicólico en la cirrosis biliar primaria.

Acerca del conjunto de evidencia para esta pregunta

Cuál es la evidencia (Véase matriz de evidencia en Epistemonikos más abajo).

Encontramos 4 revisiones sistemáticas [1],[2],[3],[4], que incluyen 16 estudios controlados aleatorizados, reportados en 104 referencias [5-108]*, que comparan ácido ursodeoxicólico versus placebo o no tratamiento en pacientes con cirrosis biliar primaria.

Qué tipo de pacientes incluyeron los estudios.

Casi 90% de los pacientes fueron mujeres. El porcentaje de pacientes con cirrosis biliar avanzada al inicio de los estudios fluctuó entre 15 y 83%.

Qué tipo de intervenciones incluyeron los estudios.

La dosis varió entre 7,7 a 15 mg/kg/día (mediana=10 mg). La duración del tratamiento fue entre 3 y 92 meses (mediana=24 meses).

Qué tipo de desenlaces midieron.

Mortalidad, necesidad de trasplante, morbilidad asociada al daño hepático crónico, síntomas, calidad de vida, efectos adversos atribuibles al medicamento. También se midieron desenlaces sustitutos como parámetros bioquímicos e histología hepática.

*Por razones de espacio, estas referencias no se desglosaron. Se puede acceder a ellas a través del acápite de Referencias.

Resumen de los resultados

La siguiente información está basada en 16 estudios aleatorizados que incluyen 1447 pacientes.

  • El ácido ursodeoxicólico podría no disminuir el prurito en pacientes con cirrosis biliar primaria. La certeza de la evidencia es baja.
  • Existe incertidumbre sobre si el ácido ursodeoxicólico aumenta o disminuye la mortalidad, la necesidad de trasplante, la morbilidad asociada al daño hepático crónico, los síntomas, o la calidad de vida, porque la calidad de la evidencia es muy baja.

Matriz de ácido ursodeoxicólico en cirrosis biliar primaria.

Otras consideraciones para la toma de decisión

A quién se aplica y a quién no se aplica esta evidencia
  • Debido a que los estudios evalúan pacientes con cirrosis biliar primaria con distintos niveles de gravedad y síntomatología, esta evidencia se aplica a prácticamente todas las personas con esta condición.
  • El análisis por subgrupo realizado por la revisión Cochrane [3], que sin duda consituye la mejor evidencia existente para esta pregunta, no mostró diferencias en ningún subgrupo evaluado (diferentes duraciones de tratamiento y diferentes dosis).
  • Es discutible si se puede aplicar o no esta evidencia a pacientes con otras enfermedades autoinmunes con compromiso hepático. Debido a que en general el uso de ácido ursodeoxicólico en otras condiciones es una extrapolación de su efecto en cirrosis biliar primaria, creemos que este resumen aporta información importante en estos casos.
Sobre los desenlaces incluidos en este resumen
  • Este resumen, al igual que las principales guías, considera la mortalidad y la necesidad de tranplante como desenlaces críticos para la toma de decisión.
  • No se ha incluido el desenlace “alteraciones en biopsia hepática” ni “alteración de pruebas hepáticas” en el resumen, ya que se trata de un desenlace sustituto, y la certeza de la evidencia para estos también es baja o muy baja.
Balance riesgo/beneficio y certeza de la evidencia
  • No es posible realizar un balance riesgo/beneficio, debido a que si bien los riesgos son pocos, existe incertidumbre sobre los beneficios.
  • La utilización de ácido ursodeoxicólico solo en el contexto de un estudio clínico parece lo más justificado.
Qué piensan los pacientes y sus tratantes
  • Debido a la escasa disponibilidad de medidas terapéuticas eficaces en esta condición, en escenarios en que no existan limitaciones de recursos, algunos pacientes y tratantes podrían inclinarse por la utilización de una terapia no probada, a pesar de sus efectos adversos y costos. En estos casos, es particularmente relevante informar al paciente sobre la certeza de la evidencia.
Consideraciones de recursos
  • En la actualidad el ácido ursodeoxicólico es un medicamento de elevado costo.
  • Debido a la incertidumbre sobre los beneficios, no es posible realizar un análisis sobre costo/beneficio.
  • En contextos en que existen limitaciones de recursos, la utilización de ácido ursodeoxicólico no parece apropiada.
Diferencias entre este resumen y otras fuentes
  • Los mensajes clave de nuestro resumen son concordantes con las conclusiones de las revisiones sistemáticas individuales identificadas [1],[2],[3],[4].
  • Los mensajes clave de nuestro resumen son discordantes con las guías de práctica de la AASLD y EASL, que son las más habitualmente citadas [109],[110]. Estas recomiendan fuertemente su uso. Ninguna de las guías incluye la última versión de la revisión sistemática Cochrane [3], que es sin lugar a dudas la mejor evidencia disponible para esta pregunta (ver matriz de evidencia). El principal argumento que ofrecen las guías para no considerar lo que ya mostraban las revisiones sistemáticas previas es que el seguimiento de los estudios era corto, lo cual ya no constituye un argumento válido.
¿Puede que cambie esta información en el futuro?
  • Existe una muy alta probabilidad de que lo que sabemos sobre ácido ursodeoxicólico en cirrosis biliar primaria cambie en el futuro si apareciera nueva evidencia.
  • Lamentablemente, hasta donde sabemos, no existen estudios en curso evaluando esta pregunta. Esto es particularmente preocupante ya que se trata de una intervención de alto costo, que es ampliamente indicada en la actualidad.


Cómo realizamos este resumen
Mediante métodos automatizados y colaborativos recopilamos toda la evidencia relevante para la pregunta de interés y la presentamos en una matriz de evidencia (esta vez la presentamos en cinco partes debido a la longitud de la matriz que incluye 104 estudios individuales).

Matriz de evidencia.
Siga el enlace para acceder a la versión interactiva: Ácido ursodeoxicólico en cirrosis biliar primaria

Notas

Si con posterioridad a la publicación de este resumen se publican nuevas revisiones sistemáticas sobre este tema, en la parte superior de la matriz se mostrará un aviso de “nueva evidencia”. Si bien el proyecto contempla la actualización periódica de estos resúmenes, los usuarios están invitados a comentar en Medwave o contactar a los autores mediante correo electrónico si creen que hay evidencia que motive una actualización más rápida.

Luego de crear una cuenta en Epistemonikos, al guardar las matrices recibirá notificaciones automáticas cada vez que exista nueva evidencia que potencialmente responda a esta pregunta.

El detalle de los métodos para elaborar este resumen están descritos aquí http://dx.doi.org/10.5867/medwave.2014.06.5997.

La Fundación Epistemonikos es una organización que busca acercar la información a quienes toman decisiones en salud, mediante el uso de tecnologías. Su principal desarrollo es la base de datos Epistemonikos (www.epistemonikos.org).

Los resúmenes de evidencia siguen un riguroso proceso de revisión por pares interno.

Los autores declaran no tener conflictos de intereses con la materia de este artículo.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Ursodeoxycholic acid is considered as first line treatment in patients with primary biliary cirrhosis. Its mechanism of action in this disease is unknown and there is controversy about its clinical impact. Searching in Epistemonikos database, which is maintained by screening 19 databases, we identified four systematic reviews including 16 studies. We combined the evidence using tables with summary of findings following the GRADE approach and concluded ursodeoxycholic acid may not have any effect on pruritus, and there is uncertainty about its effect on mortality, need for liver transplantation or on any other important outcome for the patient.

Autores: Gabriel Rada[1,2,3,4,5], Macarena Mac-Namara[1,2]

Filiación:
[1] Programa de Salud Basada en Evidencia, Facultad de Medicina, Pontificia Universidad Católica de Chile
[2] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile
[3] GRADE working group
[4] The Cochrane Collaboration
[5] Fundación Epistemonikos

E-mail: radagabriel@epistemonikos.org

Correspondencia a:
[1] Facultad de Medicina
Pontificia Universidad Católica de Chile
Lira 63,
Santiago Centro
Chile

Citación: Rada G, Mac-Namara M. Is ursodeoxycholic acid effective in primary biliary cirrhosis?. Medwave 2014 Sep;14(8):e6019 doi: 10.5867/medwave.2014.08.6019

Fecha de publicación: 24/9/2014

Ficha PubMed

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