{"id":5542,"date":"2023-05-11T06:30:38","date_gmt":"2023-05-11T09:30:38","guid":{"rendered":"https:\/\/gastropedia.pub\/pt\/?p=5542"},"modified":"2025-03-03T18:26:49","modified_gmt":"2025-03-03T21:26:49","slug":"abordagem-de-pacientes-com-alteracoes-de-enzimas-hepaticas","status":"publish","type":"post","link":"https:\/\/gastropedia.pub\/pt\/gastroenterologia\/figado\/abordagem-de-pacientes-com-alteracoes-de-enzimas-hepaticas\/","title":{"rendered":"Abordagem de pacientes com altera\u00e7\u00f5es de enzimas hep\u00e1ticas"},"content":{"rendered":"<div class=\"pdfprnt-buttons pdfprnt-buttons-post pdfprnt-top-right\"><a href=\"https:\/\/gastropedia.pub\/pt\/wp-json\/wp\/v2\/posts\/5542?print=pdf\" class=\"pdfprnt-button pdfprnt-button-pdf\" target=\"_blank\" ><img decoding=\"async\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/plugins\/pdf-print\/images\/pdf.png\" alt=\"image_pdf\" title=\"Ver PDF\" \/><\/a><a href=\"https:\/\/gastropedia.pub\/pt\/wp-json\/wp\/v2\/posts\/5542?print=print\" class=\"pdfprnt-button pdfprnt-button-print\" target=\"_blank\" ><img decoding=\"async\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/plugins\/pdf-print\/images\/print.png\" alt=\"image_print\" title=\"Conte\u00fado de impress\u00e3o\" \/><\/a><\/div>\n<p>Altera\u00e7\u00f5es de enzimas hep\u00e1ticas s\u00e3o frequentemente encontrados em pacientes assintom\u00e1ticos durante acompanhamento de rotina.<\/p>\n\n\n\n<p>\u00c9 importante atentar que o termo \u201ctestes (ou provas) de fun\u00e7\u00e3o hep\u00e1tica\u201d apesar de usualmente empregado, pode ser interpretado erroneamente, pois na maior parte das vezes essas altera\u00e7\u00f5es evidenciam dano ou les\u00e3o hep\u00e1tica, e n\u00e3o necessariamente altera\u00e7\u00e3o da fun\u00e7\u00e3o do \u00f3rg\u00e3o. Ou seja, as enzimas hep\u00e1ticas podem estar alteradas mesmo em pacientes com a fun\u00e7\u00e3o do f\u00edgado preservada.<\/p>\n\n\n\n<p>A avalia\u00e7\u00e3o do paciente deve ser feita com anamnese e exame f\u00edsico detalhados, com o intuito de pesquisar sinais e sintomas cl\u00ednicos, estigmas de hepatopatia cr\u00f4nica, hist\u00f3rias epidemiol\u00f3gica e social, uso de medica\u00e7\u00f5es e presen\u00e7a de comorbidades que sugiram a etiologia.<\/p>\n\n\n\n<p>&nbsp;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-do-ponto-de-vista-didatico-os-testes-laboratoriais-podem-ser-assim-divididos\"><strong>Do ponto de vista did\u00e1tico, os testes laboratoriais podem ser assim divididos:<\/strong><\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Aminotransferases: alanina aminotransferase (ALT) e aspartato aminotransferase (AST) &nbsp;&#8211; &nbsp; avaliam les\u00e3o hepatocelular <\/li>\n\n\n\n<li>Fosfatase alcalina (FA), Gamaglutamil transferase (GGT) e Bilirrubinas &#8211;  avaliam colestase<\/li>\n\n\n\n<li>Albumina, Tempo de protrombina, INR (&#8220;<em>international normalized ratio<\/em>&#8220;) &#8211; avaliam fun\u00e7\u00e3o hep\u00e1tica, s\u00edntese proteica<\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-testes-para-avaliacao-de-lesao-hepatocelular\"><strong>Testes para avalia\u00e7\u00e3o de les\u00e3o hepatocelular<\/strong><\/h2>\n\n\n\n<p>A avalia\u00e7\u00e3o da les\u00e3o hepatocelular \u00e9 bem determinada pelos n\u00edveis de ALT e AST. Com o dano hep\u00e1tico, os hepat\u00f3citos se rompem e as enzimas extravasam para o plasma e se tornam marcadores diagn\u00f3sticos de les\u00e3o do f\u00edgado.<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; A AST est\u00e1 presente no f\u00edgado e em outros \u00f3rg\u00e3os como cora\u00e7\u00e3o e musculatura. Em virtude disso, \u00e9 preciso cautela na interpreta\u00e7\u00e3o quanto ao seu aumento isolado. A ALT est\u00e1 presente principalmente no f\u00edgado e por isso \u00e9 mais espec\u00edfica como marcador de inj\u00faria hep\u00e1tica.<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Os n\u00edveis considerados como normais para aminotransferases tem sido questionado, e estima-se que os valores verdadeiramente normais sejam mais baixos que os atualmente adotados. Deve-se levar em conta ainda que o sexo, a idade e os m\u00e9todos utilizados tamb\u00e9m influenciam nessa determina\u00e7\u00e3o. Assim, deve-se considerar o n\u00famero de vezes em que est\u00e1 aumentado com rela\u00e7\u00e3o ao limite superior da normalidade (LSN), de forma a permitir compara\u00e7\u00f5es.<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Nas hepatites agudas (virais ou t\u00f3xicas), os n\u00edveis de ALT s\u00e3o maiores que os de AST. Na hepatite fulminante, tanto ALT quanto AST, est\u00e3o bastante aumentadas nos primeiros dias de doen\u00e7a e \u00e9 seguida de uma queda abrupta e at\u00e9 n\u00edveis normais.&nbsp; Na doen\u00e7a hep\u00e1tica alco\u00f3lica, h\u00e1 uma despropor\u00e7\u00e3o entre AST e ALT que chama aten\u00e7\u00e3o. Isso ocorre pela les\u00e3o mitocondrial que o \u00e1lcool causa (AST\/ALT &gt; 2).&nbsp; As duas enzimas podem chegas a n\u00edveis maiores que 5000UI\/L em situa\u00e7\u00e3o de isquemia aguda hep\u00e1tica.<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Nas hepatites cr\u00f4nicas, \u00e9 comum o aumento das duas enzimas entre 2-40 vezes o LSN e a rela\u00e7\u00e3o AST\/ALT &lt; 1, mas pode ser &gt; 1 quando h\u00e1 evolu\u00e7\u00e3o para cirrose hep\u00e1tica. Vale ressaltar, que as enzimas podem estar normais mesmo em pacientes com cirrose ou outra doen\u00e7a hep\u00e1tica cr\u00f4nica. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Valores baixos das enzimas podem subestimar atividade necroinflamat\u00f3ria nos quadros de hepatopatias cr\u00f4nicas, como &nbsp;&nbsp;hepatite autoimune, hepatites pelos v\u00edrus B e C, por exemplo \u2013 j\u00e1 que nessas situa\u00e7\u00f5es pode haver uma dissocia\u00e7\u00e3o entre os n\u00edveis enzim\u00e1ticos e os achados histopatol\u00f3gicos.<\/p>\n\n\n\n<p>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Nas doen\u00e7as obstrutivas da via biliar, pode haver aumento das aminotransferases at\u00e9 30 vezes o LSN, o que pode dificultar o diagn\u00f3stico. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Na tabela 1 est\u00e3o apresentadas as principais causas de eleva\u00e7\u00e3o de aminotransferases<\/p>\n\n\n\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-9d6595d7 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\" style=\"flex-basis:100%\">\n<figure class=\"wp-block-table\"><div class=\"pcrstb-wrap\"><table><tbody><tr><td><strong>Hepatotoxicidade<\/strong><\/td><\/tr><tr><td>\u00c1lcool, drogas, ervas<\/td><\/tr><tr><td><strong>Causas infecciosas<\/strong><\/td><\/tr><tr><td>Hepatites virais A, B, C, D, E; herpes simples; varicela; citomegalov\u00edrus; Epstein-Barr e outros.<\/td><\/tr><tr><td><strong>Doen\u00e7as imunomediadas<\/strong><\/td><\/tr><tr><td>Hepatite autoimune<\/td><\/tr><tr><td>S\u00edndromes de sobreposi\u00e7\u00e3o<\/td><\/tr><tr><td><strong>Doen\u00e7as hep\u00e1ticas metab\u00f3licas<\/strong><\/td><\/tr><tr><td>Doen\u00e7a de Wilson (DW)<\/td><\/tr><tr><td>Hemocromatose<\/td><\/tr><tr><td>Doen\u00e7a hep\u00e1tica gordurosa n\u00e3o alco\u00f3lica (DHGNA)<\/td><\/tr><tr><td><strong>Doen\u00e7as hep\u00e1ticas vasculares<\/strong><\/td><\/tr><tr><td>Hepatite isqu\u00eamica<\/td><\/tr><tr><td>S\u00edndrome de Budd-Chiari<\/td><\/tr><tr><td>S\u00edndrome de obstru\u00e7\u00e3o sinusoidal<\/td><\/tr><tr><td><strong>Outras causas<\/strong><\/td><\/tr><tr><td>Esquistossomose<\/td><\/tr><tr><td>Doen\u00e7a cel\u00edaca<\/td><\/tr><tr><td>Defici\u00eancia de alfa-1 antitripsina<\/td><\/tr><tr><td>Doen\u00e7as granulomatosas: sarcoidose, tuberculose<\/td><\/tr><tr><td>Doen\u00e7as reumatol\u00f3gicas: l\u00fapus eritematoso sist\u00eamico, atrite reumatoide<\/td><\/tr><\/tbody><\/table><\/div><figcaption class=\"wp-element-caption\"><strong>Tabela 1- Causas de eleva\u00e7\u00e3o de aminotransferases<\/strong><\/figcaption><\/figure>\n<\/div>\n<\/div>\n<\/div><\/div>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-testes-para-avaliacao-da-colestase\"><strong>Testes para avalia\u00e7\u00e3o da colestase <\/strong><\/h2>\n\n\n\n<p>A colestase \u00e9 uma obstru\u00e7\u00e3o, anat\u00f4mica ou funcional, \u00e0 excre\u00e7\u00e3o da bile. As enzimas que se localizam na membrana canalicular do hep\u00e1tico e ductos biliares \u2013 FA e GGT &#8211; s\u00e3o as que ajudam nesse diagn\u00f3stico.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Gamaglutamil transferase<\/strong><\/li>\n<\/ul>\n\n\n\n<p>O aumento da GGT tem alta sensibilidade para doen\u00e7a hep\u00e1tica, mas baixa especificidade, j\u00e1 que pode aumentar em pacientes com pancreatite, hipertireoidismo, artrite reumatoide e infarto do mioc\u00e1rdio. \u00c9 uma enzima facilmente induzida e seus n\u00edveis podem-se elevar com a ingest\u00e3o de alguns medicamentos (fenito\u00edna e barbit\u00faricos, por exemplo) e do \u00e1lcool.<\/p>\n\n\n\n<p>Eleva\u00e7\u00f5es importantes de GGT (at\u00e9 70 vezes o LSN) podem ser vistas em doen\u00e7as obstrutivas do trato biliar, por exemplo. Nas hepatites agudas, os valores de GGT raramente ultrapassam 10 vezes o LSN, exceto nas formas colest\u00e1ticas da doen\u00e7a.&nbsp; J\u00e1 nas hepatites cr\u00f4nicas a altera\u00e7\u00e3o tende a ser discreta.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Fosfatase alcalina<\/strong><\/li>\n<\/ul>\n\n\n\n<p>A fun\u00e7\u00e3o exata dessa enzima \u00e9 desconhecida. \u00c9 encontrada em v\u00e1rios \u00f3rg\u00e3os e tecidos, como placenta, mucosa intestinal e membrana canalicular dos hepat\u00f3citos. A atividade da FA s\u00e9rica \u00e9 derivada de tr\u00eas fontes: f\u00edgado, ossos e trato gastrointestinal.&nbsp; Os valores normais variam muito.<\/p>\n\n\n\n<p>Em casos de aumento de FA, dosagem s\u00e9rica de GGT e bilirrubinas podem ser utilizadas para confirmar a origem hep\u00e1tica. Se confirmado, \u00e9 preciso definir se a colestase \u00e9 de origem intra ou extra-hep\u00e1tica. Nesse ponto, a realiza\u00e7\u00e3o de imagem abdominal ser\u00e1 necess\u00e1ria. Na tabela 2 est\u00e3o apresentadas as principais de aumento de FA e GGT.<\/p>\n\n\n\n<figure class=\"wp-block-table\"><div class=\"pcrstb-wrap\"><table><tbody><tr><td rowspan=\"14\"><strong>Eleva\u00e7\u00f5es &gt; 3x o LSN de ambas as enzimas<\/strong><strong><\/strong><\/td><td><strong>Obstru\u00e7\u00e3o extra-hep\u00e1tica<\/strong><\/td><\/tr><tr><td>Coledocolit\u00edase<\/td><\/tr><tr><td>Obstru\u00e7\u00e3o tumoral<\/td><\/tr><tr><td>Colangite esclerosante prim\u00e1ria (CEP)<\/td><\/tr><tr><td>Colangiopatia do HIV<\/td><\/tr><tr><td><strong>Colestase intra-hep\u00e1tica<\/strong><\/td><\/tr><tr><td>Drogas<\/td><\/tr><tr><td>Colangite biliar prim\u00e1ria (CBP)<\/td><\/tr><tr><td>CEP pequenos ductos<\/td><\/tr><tr><td>Colestase benigna<\/td><\/tr><tr><td>Nutri\u00e7\u00e3o parenteral total<\/td><\/tr><tr><td>Doen\u00e7as infiltrativas<\/td><\/tr><tr><td>    linfomas, met\u00e1stases<\/td><\/tr><tr><td>Outras colangiopatias (ex.: colangiopatia por IgG4)<\/td><\/tr><tr><td rowspan=\"5\"><strong>Eleva\u00e7\u00f5es &lt; 3x o LSN de ambas as enzimas<\/strong><strong><\/strong><\/td><td><strong>Doen\u00e7as hepatocelulares<\/strong><\/td><\/tr><tr><td>Hepatites: viral, cr\u00f4nica, alco\u00f3lica<\/td><\/tr><tr><td>Cirrose<\/td><\/tr><tr><td>Doen\u00e7as infiltrativas<\/td><\/tr><tr><td>Estados hipoperfusionais: sepse, fal\u00eancia card\u00edaca<\/td><\/tr><\/tbody><\/table><\/div><figcaption class=\"wp-element-caption\"><strong>Tabela 2- <\/strong>Causas de aumento de FA e GGT<\/figcaption><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-algoritimo-para-investigacao-de-testes-hepaticos-alterados\"><strong>Algor\u00edtimo para investiga\u00e7\u00e3o de testes hep\u00e1ticos alterados <\/strong><\/h2>\n\n\n\n<p>A avalia\u00e7\u00e3o das altera\u00e7\u00f5es dos testes hep\u00e1ticos deve ser feita em conjunto, levando-se em conta se a altera\u00e7\u00e3o \u00e9 em um \u00fanico teste ou em conjunto com os demais, o que ir\u00e1 direcionar o racioc\u00ednio cl\u00ednico. Assim, na investiga\u00e7\u00e3o de um teste hep\u00e1tico alterado, deve-se partir da altera\u00e7\u00e3o predominante, ou seja:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Altera\u00e7\u00e3o de ALT e AST predomina sobre altera\u00e7\u00e3o de FA e GGT(Figura 1)<\/li>\n\n\n\n<li>Altera\u00e7\u00e3o de FA e GGT predomina sobre altera\u00e7\u00e3o de AST e ALT(Figura 2)<\/li>\n<\/ul>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><a href=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image.png\" data-rel=\"penci-gallery-image-content\" ><img fetchpriority=\"high\" decoding=\"async\" width=\"572\" height=\"504\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image.png\" alt=\"\" class=\"wp-image-5543\" style=\"width:572px;height:504px\" srcset=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image.png 572w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image-300x264.png 300w\" sizes=\"(max-width: 572px) 100vw, 572px\" \/><\/a><figcaption class=\"wp-element-caption\"><strong>Figura 1: Investiga\u00e7\u00e3o da eleva\u00e7\u00e3o das aminotransferases<br><\/strong><\/figcaption><\/figure>\n<\/div>\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter size-full is-resized\"><a href=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image-1.png\" data-rel=\"penci-gallery-image-content\" ><img decoding=\"async\" width=\"728\" height=\"530\" src=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image-1.png\" alt=\"\" class=\"wp-image-5545\" style=\"width:728px;height:530px\" srcset=\"https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image-1.png 728w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image-1-300x218.png 300w, https:\/\/gastropedia.pub\/pt\/wp-content\/uploads\/2023\/05\/image-1-585x426.png 585w\" sizes=\"(max-width: 728px) 100vw, 728px\" \/><\/a><figcaption class=\"wp-element-caption\"><strong>Figura 2: Investiga\u00e7\u00e3o de eleva\u00e7\u00e3o de FA e GGT. <\/strong><br><strong><strong>CPRE: colangiopancreatografia retr\u00f3grada endosc\u00f3pica<\/strong><br><\/strong><\/figcaption><\/figure>\n<\/div>\n\n\n<p>Caso o diagn\u00f3stico das altera\u00e7\u00f5es hep\u00e1ticas permane\u00e7a inconclusivo, pode-se at\u00e9 considerar uma conduta expectante para aumentos discretos de enzimas (at\u00e9 duas vezes o LSN para aminotransferases e at\u00e9 uma vez e meia para FA e GGT), com dosagens dos testes bioqu\u00edmicos e fun\u00e7\u00e3o hep\u00e1tica a cada 6 meses. Por\u00e9m, caso as altera\u00e7\u00f5es persistam, a bi\u00f3psia hep\u00e1tica deve ser considerada.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote has-pale-ocean-gradient-background has-background is-layout-flow wp-block-quote-is-layout-flow\">\n<p>Conhe\u00e7a nosso curso <strong><a href=\"https:\/\/gastropedia.pub\/pt\/cursos\/gastroenterologia-do-consultorio\/\" target=\"_blank\" rel=\"noreferrer noopener\">Gastroenterologia do Consult\u00f3rio<\/a><\/strong> e saiba como lidar com as queixas mais comuns que encontramos no dia a dia<\/p>\n<\/blockquote>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-referencias\"><strong>Refer\u00eancias<\/strong><\/h2>\n\n\n\n<ol class=\"wp-block-list\">\n<li>Newsome PN, Cramb R, et al. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67:6<\/li>\n\n\n\n<li>Pratt DS, Kaplan MM. Evaluation of abnormal liver enzyme results in asymptomatic patiets. N Engl J Med 2000; 342:1266<\/li>\n\n\n\n<li>Ferraz ML. Testes laboratoriais na investiga\u00e7\u00e3o de doen\u00e7as hep\u00e1ticas. In: Mattos AA, Dantas-Correa EB. Tratado de Hepatologia. Rio de Janeiro:Rubio,2010. p.21-28.<\/li>\n\n\n\n<li>Ioannou GN, Implications of elevated serum alanine aminotransferase levels: think outside de liver. Gastroenterol 2008; 135 (6):1851-1854<\/li>\n\n\n\n<li>Imagem de capa <a href=\"https:\/\/br.freepik.com\/fotos-gratis\/medico-realizando-pesquisas-medicas-em-laboratorio_24236669.htm#query=exames%20laboratoriais&amp;position=5&amp;from_view=search&amp;track=ais\" target=\"_blank\" rel=\"noreferrer noopener\">Freepik<\/a><\/li>\n<\/ol>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"h-como-citar-este-artigo\"><strong>Como citar este artigo<\/strong><\/h2>\n\n\n\n<p class=\"has-background\" style=\"background-color:#acdbf2\">Medeiros M. Abordagem de pacientes com altera\u00e7\u00f5es de testes hep\u00e1ticos. Gastropedia 2023, Vol. 1. Dispon\u00edvel em: <a href=\"https:\/\/gastropedia.pub\/pt\/?p=5542\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/gastropedia.pub\/pt\/gastroenterologia\/abordagem-de-pacientes-com-alteracoes-de-testes-hepaticos<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Altera\u00e7\u00f5es de enzimas hep\u00e1ticas s\u00e3o frequentemente encontrados em pacientes assintom\u00e1ticos durante acompanhamento de rotina. \u00c9 importante atentar que o termo \u201ctestes (ou provas) de fun\u00e7\u00e3o hep\u00e1tica\u201d apesar de usualmente empregado,&hellip;<\/p>\n","protected":false},"author":5677,"featured_media":6609,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[21,18],"tags":[],"ano":[137],"tipo":[121],"volume":[57],"class_list":["post-5542","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-figado","category-gastroenterologia","ano-137","tipo-assuntos-gerais","volume-volume-i"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.2 (Yoast SEO v27.3) - 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