{"id":8068,"date":"2023-03-30T06:30:23","date_gmt":"2023-03-30T04:30:23","guid":{"rendered":"https:\/\/gastropedia.pub\/es\/?p=8068"},"modified":"2025-05-10T00:46:16","modified_gmt":"2025-05-09T22:46:16","slug":"investigacion-de-hepatitis-medicamentosa-drug-induced-liver-injury-dili-conceptos-principales-y-linea-de-razonamiento","status":"publish","type":"post","link":"https:\/\/gastropedia.pub\/es\/gastroenterologia\/investigacion-de-hepatitis-medicamentosa-drug-induced-liver-injury-dili-conceptos-principales-y-linea-de-razonamiento\/","title":{"rendered":"Investigaci\u00f3n de Hepatitis Medicamentosa (Drug-Induced Liver Injury \u2013 DILI): conceptos principales y l\u00ednea de razonamiento"},"content":{"rendered":"

Aspectos Generales<\/strong><\/h2>\n

La hepatitis medicamentosa (Drug-induced liver injury, DILI) <\/em>es uno de los cuadros m\u00e1s desafiantes en Hepatolog\u00eda debido a la amplia disponibilidad de medicamentos, suplementos y hierbas con potencial de hepatotoxicidad heterog\u00e9neo, variando desde una leve elevaci\u00f3n de enzimas hep\u00e1ticas hasta hepatitis aguda pronunciada e insuficiencia hep\u00e1tica fulminante (IHF).<\/p>\n

Tradicionalmente, DILI<\/em> puede clasificarse como intr\u00ednseca (o directa) versus<\/em> idiosincr\u00e1sica. La primera es t\u00edpicamente relacionada con la dosis y ocurre en la mayor\u00eda de los pacientes expuestos a un medicamento, ocurriendo dentro de un corto per\u00edodo de tiempo (horas a d\u00edas). Ya DILI<\/em> idiosincr\u00e1sica usualmente no es dependiente de la dosis, ocurre en una menor proporci\u00f3n de individuos expuestos (impredecible) y presenta una latencia variable entre d\u00edas a semanas.<\/p>\n

Un prerrequisito com\u00fan para DILI<\/em> intr\u00ednseca e idiosincr\u00e1sica es el metabolismo de drogas lipof\u00edlicas en el h\u00edgado, generando metabolitos reactivos que llevan a la uni\u00f3n covalente, estr\u00e9s oxidativo mitocondrial y del ret\u00edculo endoplasm\u00e1tico. Tales consecuencias pueden resultar (a) directamente en necrosis o apoptosis [intr\u00ednseca] o (b) en respuesta inmune adaptativa [idiosincr\u00e1sica] en individuos gen\u00e9ticamente susceptibles. Las principales drogas relacionadas con DILI se encuentran en la Tabla 1.<\/p>\n

\"\"<\/p>\n

\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Tabla 1. Drogas associadas con DILI<\/em> intr\u00ednseca e idiosincr\u00e1sica<\/strong><\/figcaption><\/figure>\n

 <\/p>\n

Patrones de DILI<\/strong><\/h2>\n

Existen 3 patrones de DILI<\/em> evaluados por la elevaci\u00f3n de enzimas hep\u00e1ticas:<\/p>\n

    \n
  • Hepatocelular<\/strong>: si ALT aislada \u2265 5x l\u00edmite superior de la normalidad (LSN) o Factor R \u2265\u00a05<\/li>\n
  • Colest\u00e1tico<\/strong>: si FA aislada \u2265\u00a0 2x LSN o Factor R \u2265\u00a0 2<\/li>\n
  • Mixto: <\/strong>Factor R > 2 a < 5<\/li>\n<\/ul>\n

     <\/p>\n

    Recomendaci\u00f3n<\/strong><\/h2>\n

    DILI debe ser clasificada como hepatocelular, colest\u00e1tica o mixta de acuerdo con el patr\u00f3n de elevaci\u00f3n de enzimas hep\u00e1ticas de la primera dosificaci\u00f3n de laboratorio en relaci\u00f3n al evento cl\u00ednico. Grado B (EASL, 2019).<\/p>\n

    T\u00e9s, Hierbas y Fitoter\u00e1picos<\/strong><\/h2>\n

    La hepatotoxicidad por t\u00e9s, hierbas, fitoter\u00e1picos y suplementos est\u00e1 relacionada a diferentes factores que coexisten: falta de adecuada identificaci\u00f3n de la planta, selecci\u00f3n de la parte errada de la planta medicinal, almacenamiento inadecuado modificando el producto nativo, adulteraci\u00f3n durante el procesamiento y etiquetado incorrecto del producto.<\/p>\n

    Otro desaf\u00edo es la falta de claridad en la real composici\u00f3n de preparaciones a base de plantas, en especial, de multicomponentes. Se resalta a\u00fan que un producto fitoter\u00e1pico puede ser contaminado por compuestos t\u00f3xicos que llevan a la hepatotoxicidad, como contaminaci\u00f3n por metales pesados, pesticidas, herbicidas o incluso microorganismos.<\/p>\n

    Se destacan algunos fitoter\u00e1picos que poseen nivel de evidencia de hepatotoxicidad:<\/p>\n

      \n
    • Plantas que contienen alcaloides pirrolizid\u00ednicos (especies Heliotropium, Senecia, Crotalaria, Symphytum <\/em>y Gynura<\/em>)<\/li>\n
    • Germander (\u201ccola de caballo\u201d)<\/li>\n
    • Kava-kava (Piper methysticum)<\/em><\/li>\n
    • T\u00e9 verde (Camellia sinensis)<\/em><\/li>\n
    • Sena (Cassia angustifolia)<\/em><\/li>\n
    • Sacaca (Croton cajucara benth)<\/em><\/li>\n
    • Chaparral (Larrea tridentata)<\/em><\/li>\n
    • P<\/em>oleo (Mentha pulegium)<\/em><\/li>\n
    • C<\/em>\u00e1scara sagrada (Rhamnus purshiana<\/em>)<\/li>\n
    • Hierba de San Crist\u00f3bal (Cimicifuga racemosa<\/em>)<\/li>\n
    • Noni (Morinda citrifolia)<\/em>, entre otras<\/li>\n<\/ul>\n

      Entre los suplementos alimentarios, se destacan:<\/p>\n

        \n
      • Contiene \u00e1cido \u00fasnico (LipoKinetix, UCP-1, OxyElite)<\/li>\n
      • Hydroxycut<\/li>\n
      • \u00c1cido linoleico<\/li>\n
      • Plethoryl (vitamina A y hormonas tiroideas)<\/li>\n
      • Esteroides anabolizantes androg\u00e9nicos<\/li>\n<\/ul>\n

        Recomendaci\u00f3n<\/strong><\/h2>\n

        Los suplementos alimentarios y fitoter\u00e1picos pueden ser considerados como potenciales agentes causantes de inj\u00faria hep\u00e1tica. Grado C (EASL, 2019).<\/p>\n

        Causalidad \u2013 Puntuaciones<\/strong><\/h2>\n

        Algunas puntuaciones pueden ser utilizadas en la evaluaci\u00f3n de causalidad para DILI<\/em>, de forma que los criterios de cronolog\u00eda (inicio y suspensi\u00f3n de la droga), curso de la reacci\u00f3n, factores de riesgo, exclusi\u00f3n de otras causas, manifestaciones extrahep\u00e1ticas, reexposici\u00f3n, entre otros aspectos, son puntuados y clasificados en exclusi\u00f3n o diagn\u00f3stico posible, probable o definitivo para DILI<\/em>:<\/p>\n

          \n
        • Council for International Organizations of Medical Sciences Scale\/Roussel-Uclaf-Causality-Assessment-Method (CIOMS\/RUCAM);<\/li>\n
        • Clinical Diagnostic Scale\/Maria and Victorino Scale (CDS\/M&V scale);<\/li>\n
        • Digestive Disease Week-Japan (DDW-J);<\/li>\n
        • DILIN Expert Opinion.<\/li>\n<\/ul>\n

          Se debe tener en mente, sin embargo, que las puntuaciones no sustituyen el juicio cl\u00ednico, siendo, en realidad, una traducci\u00f3n, en puntuaci\u00f3n cuantitativa, de la sospecha cl\u00ednica de DILI<\/em>.<\/p>\n

          Evaluaci\u00f3n Laboratorial para Exclusi\u00f3n de Causas Alternativas<\/strong><\/h2>\n

          El diagn\u00f3stico de DILI<\/em> se basa en la exclusi\u00f3n<\/strong> de causas alternativas de agresi\u00f3n hep\u00e1tica. El patr\u00f3n de inj\u00faria hep\u00e1tica puede auxiliar en la investigaci\u00f3n inicial para descartar las principales causas de hepatitis y colestasis (Figura 1).<\/p>\n

          Adem\u00e1s, la edad y las comorbilidades, los h\u00e1bitos individuales de los pacientes y las caracter\u00edsticas regionales de enfermedades infecciosas que pueden afectar el h\u00edgado pueden guiar en la evaluaci\u00f3n (Tabla 2) .<\/p>\n

          La exclusi\u00f3n de la enfermedad de Wilson con dosificaci\u00f3n de ceruloplasmina debe ser realizada, en especial, en pacientes con menos de 40 a\u00f1os.<\/p>\n

          \"\"<\/p>\n

          \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0Tabla 1. Diagrama de flujo de investigaci\u00f3n de DILI<\/strong>\"\"<\/strong><\/p>\n

          \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 Tabla 2. Enfermedades hep\u00e1ticas y ex\u00e1menes en la investigaci\u00f3n diagn\u00f3stica\u00a0<\/strong><\/p>\n

          Recomendaci\u00f3n<\/strong><\/h2>\n

          La ecograf\u00eda abdominal debe ser realizada en todos los pacientes con sospecha de DILI. Un examen de imagen adicional podr\u00e1 ser indicado de acuerdo con el contexto cl\u00ednico-laboratorial. Grado B (EASL, 2019).<\/p>\n

          Recomendaci\u00f3n<\/strong><\/h2>\n

          La biopsia hep\u00e1tica puede ser considerada en pacientes seleccionados sospechosos para DILI, de forma que la histolog\u00eda hep\u00e1tica pueda proporcionar informaciones que fundamenten el diagn\u00f3stico de DILI o una alternativa (Grado D) o cuando los ex\u00e1menes levanten la posibilidad de HAI (Grado C); EASL, 2019.<\/p>\n

          Conclusi\u00f3n<\/strong><\/h2>\n

          En resumen, el principal paso en el manejo de los casos de DILI<\/em> es la suspensi\u00f3n de todas las drogas no esenciales, incluyendo formulaciones, suplementos, hierbas y t\u00e9s. De esta forma, la mayor\u00eda de los pacientes cursar\u00e1 con recuperaci\u00f3n espont\u00e1nea cl\u00ednica y\/o laboratorial, sin la necesidad de medidas adicionales.<\/p>\n

          Pacientes con evidencia cl\u00ednica o laboratorial de IHF, como encefalopat\u00eda hep\u00e1tica o coagulopat\u00eda, deben ser hospitalizados.<\/p>\n

          En general, la terapia medicamentosa queda reservada para situaciones espec\u00edficas, como n-acetilciste\u00edna en la intoxicaci\u00f3n por paracetamol o DILI<\/em> idiosincr\u00e1sica con IHF o corticoides, si hay la posibilidad de hepatitis autoinmune o en la presencia de componentes de hipersensibilidad.<\/p>\n

          La reexposici\u00f3n a la droga (\u201crechallenge\u201d)<\/em> es el dato m\u00e1s definitivo para el diagn\u00f3stico de DILI<\/em> (ALT>3xLSN), pero debe ser evaluada caso a caso, conforme la gravedad del episodio de DILI<\/em> y necesidad de la terapia medicamentosa (ejemplo: agentes quimioter\u00e1picos o tuberculost\u00e1ticos), bajo supervisi\u00f3n especializada y rigurosa.<\/p>\n

          Referencias<\/strong><\/h2>\n
            \n
          1. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, Clinical Practice Guideline Panel: Chair:, Panel members, et al<\/em>. EASL clinical practice guidelines: drug-induced liver injury. J Hepatol <\/em>2019;70:1222\u2013 61.<\/li>\n
          2. Brennan PN, Cartlidge P, Manship T, Dillon JF. Guideline review: EASL clinical practice guidelines: drug-induced liver injury (DILI). Frontline Gastroenterol. 2021 Jul 29;13(4):332-336. doi: 10.1136\/flgastro-2021-101886. PMID: 35722609; PMCID: PMC9186030.<\/li>\n
          3. Chalasani NP, Maddur H, Russo MW, Wong RJ, Reddy KR; Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. Am J Gastroenterol. 2021 May 1;116(5):878-898. doi: 10.14309\/ajg.0000000000001259. PMID: 33929376.<\/li>\n
          4. Garc\u00eda-Cort\u00e9s M, Stephens C, Lucena MI, Fern\u00e1ndez-Casta\u00f1er A, Andrade RJ. Causality assessment methods in drug induced liver injury: strengths and weaknesses. J Hepatol. 2011 Sep;55(3):683-691. doi: 10.1016\/j.jhep.2011.02.007. Epub 2011 Feb 22. PMID: 21349301.<\/li>\n
          5. Bessone F, Garc\u00eda-Cort\u00e9s M, Medina-Caliz I, Hernandez N, Parana R, Mendizabal M, Schinoni MI, Ridruejo E, Nunes V, Peralta M, Santos G, Anders M, Chiodi D, Tagle M, Montes P, Carrera E, Arrese M, Lizarzabal MI, Alvarez-Alvarez I, Caballano-Infantes E, Niu H, Pinazo J, Cabello MR, Lucena MI, Andrade RJ. Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network. Clin Gastroenterol Hepatol. 2022 Mar;20(3):e548-e563. doi: 10.1016\/j.cgh.2021.01.011. Epub 2021 Jan 9. PMID: 33434654.<\/li>\n<\/ol>\n

            C\u00f3mo citar este art\u00edculo<\/strong><\/h2>\n

            Oti KST, Gamarra ACQ. Investigaci\u00f3n de Drug-Induced Liver Injury (DILI):<\/em> principales conceptos y l\u00ednea de razonamiento. Gastropedia 2024, vol. 2. Disponible en: https:\/\/gastropedia.pub\/es\/gastroenterologia\/investigacion-de-hepatitis-medicamentosa-drug-induced-liver-injury-dili-conceptos-principales-y-linea-de-razonamiento<\/p>\n","protected":false},"excerpt":{"rendered":"

            Aspectos Generales La hepatitis medicamentosa (Drug-induced liver injury, DILI) es uno de los cuadros m\u00e1s desafiantes en Hepatolog\u00eda debido a la amplia disponibilidad de medicamentos, suplementos y hierbas con potencial…<\/p>\n","protected":false},"author":5590,"featured_media":8046,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_lmt_disableupdate":"no","_lmt_disable":"","footnotes":""},"categories":[18,21],"tags":[],"ano":[395],"tipo":[121],"volumen":[44],"class_list":["post-8068","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-gastroenterologia","category-higado","ano-395","tipo-temas-generales","volumen-volume-ii"],"yoast_head":"\nInvestigaci\u00f3n de Hepatitis Medicamentosa (Drug-Induced Liver Injury \u2013 DILI): conceptos principales y l\u00ednea de razonamiento - Gastropedia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, 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