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        "titulo" => "Hepatite autoimune em 828 crian&#231;as e adolescentes brasileiros&#58; achados cl&#237;nicos e laboratoriais&#44; perfil histol&#243;gico&#44; tratamentos e resultados"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">M&#233;todo de Kaplan&#8208;Meier para analisar a sobrevida de pacientes com hepatite autoimune&#46; A sobrevida &#233; significativamente maior nos pacientes com HAI tipo 2&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A hepatite autoimune &#40;HAI&#41; &#233; uma doen&#231;a hep&#225;tica cr&#244;nica normalmente progressiva e caracterizada histologicamente por inflama&#231;&#227;o periportal&#44; necrose em ponte&#44; forma&#231;&#227;o de rosetas &#40;<span class="elsevierStyleItalic">rosetting</span>&#41; nas c&#233;lulas hep&#225;ticas e infiltra&#231;&#227;o de c&#233;lulas plasm&#225;ticas&#46; Apesar de a etiologia ser desconhecida&#44; sua patog&#234;nese tem com base&#44; no m&#237;nimo parcialmente&#44; a autorreatividade aberrante&#46; O fen&#243;tipo cl&#225;ssico foi caracterizado por alguns marcadores sorol&#243;gicos&#44; principalmente anticorpos antinucleares&#44; anticorpos do m&#250;sculo liso &#40;SMAs&#41; e anticorpos contra a fra&#231;&#227;o microssomal de f&#237;gado e rim tipo 1 &#40;anti&#8208;LKM1s&#41;&#44; independentemente da associa&#231;&#227;o com os anticorpos anticitosol hep&#225;tico tipo 1&#44; hipergamaglobulinemia&#44; aumento nos n&#237;veis de imunoglobulina no soro &#40;Ig&#41;G&#44; hepatite de interface no exame histol&#243;gico e resposta &#224; terapia com corticosteroides&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Foram publicados estudos sobre a epidemiologia e o hist&#243;rico natural da HAI pedi&#225;trica&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">4&#44;5</span></a> o que &#233; importante&#44; considerando que a maior parte do conhecimento sobre HAI prov&#233;m de estudos em adultos&#46; Os estudos limitados em crian&#231;as demonstraram as peculiaridades dessa doen&#231;a em pacientes pedi&#225;tricos&#46; Visamos a avaliar o quadro cl&#237;nico&#44; os achados laboratoriais&#44; o perfil histol&#243;gico&#44; os tratamentos e os resultados de crian&#231;as e adolescentes com HAI na Am&#233;rica do Sul em um grande estudo com acompanhamento de longo prazo&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Este estudo multic&#234;ntrico retrospectivo&#160;foi feito para avaliar os resultados cl&#237;nicos de 828 crian&#231;as e adolescentes com hist&#243;rico de HAI bem documentado e de longo prazo de acordo com os crit&#233;rios do Grupo Internacional de Estudo da HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a> Os dados foram coletados de relat&#243;rios de centros &#250;nicos&#46; Um question&#225;rio avaliou os dados an&#244;nimos sobre as caracter&#237;sticas demogr&#225;ficas&#44; o quadro cl&#237;nico&#44; os achados bioqu&#237;micos e histol&#243;gicos e os tratamentos&#46; Os pacientes foram acompanhados de 1983 a 2015 em 17 centros de gastroenterologia&#47;hepatologia pedi&#225;trica em todo o Brasil&#46; Este estudo foi aprovado pelos comit&#234;s de &#233;tica relacionados &#40;n&#250;mero CAAE 53562116&#46;5&#46;1001&#46;0068&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Todas as crian&#231;as e adolescentes foram submetidas a um protocolo cl&#237;nico e laboratorial&#44; inclusive avalia&#231;&#227;o dos par&#226;metros bioqu&#237;micos&#44; como alanina aminotransferase&#44; aspartato aminotransferase&#44; gamaglutamiltranspeptidase &#40;GGTP&#41;&#44; fosfatase alcalina &#40;ALP&#41;&#44; albumina&#44; gamaglobulina&#44; raz&#227;o normalizada internacional &#40;INR&#41;&#44; bilirrubina total e direta &#40;DB&#41;&#44; glicose s&#233;rica&#44; triiodotironina&#44; tiroxina e horm&#244;nio estimulante da tireoide medidos com radioimunoensaio&#46; Os n&#237;veis s&#233;ricos de Ig e complementos foram medidos com nefelometria&#44; que foram expressos em g&#47;L e variaram por centro&#46; Os resultados foram registrados como normal&#44; aumentado ou reduzido&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Todos os pacientes foram examinados na apresenta&#231;&#227;o para anticorpos antinucleares&#44; anti&#8208;SMA&#44; anti&#8208;LKM1 e antimitoc&#244;ndria&#46; As amostras de soro foram tituladas at&#233; 1&#47;320&#46; Os t&#237;tulos &#62; 1&#58;40 e 1&#47;20 foram considerados positivos para anti&#8208;SMA e anti&#8208;LKM1&#44; respectivamente&#46; Al&#233;m disso&#44; os pacientes apresentaram achados negativos para o v&#237;rus da hepatite A&#44; B e C&#44; v&#237;rus da imunodefici&#234;ncia humana&#44; citomegalov&#237;rus e v&#237;rus Epstein&#8208;Barr&#46; Eles n&#227;o apresentaram hist&#243;rico de uso de drogas ou &#225;lcool nem exposi&#231;&#227;o a medicamentos hepatot&#243;xicos&#46; Foram exclu&#237;dos os pacientes com defici&#234;ncia de alfa&#8208;1 antitripsina e doen&#231;a de Wilson&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O exame de colangiografia foi feito por colangiopancreatografia por resson&#226;ncia magn&#233;tica &#40;CPRM&#41; ou por endoscopia em pacientes que n&#227;o responderam aos medicamentos imunossupressores ou apresentaram n&#237;veis aumentos de GGTP durante o monitoramento da doen&#231;a&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Foi feita bi&#243;psia hep&#225;tica em 664 &#40;80&#44;2&#37;&#41; pacientes antes do tratamento imunossupressor&#44; por meio de bi&#243;psia por agulha percut&#226;nea com uma agulha Tru&#8208;Cut ou cirurgia&#59; 253 crian&#231;as foram submetidas a mais de uma bi&#243;psia durante o acompanhamento para documentar reca&#237;das ou como um crit&#233;rio de interrup&#231;&#227;o da terapia por dois anos&#44; em casos de remiss&#245;es cl&#237;nicas e bioqu&#237;micas&#46; As se&#231;&#245;es embebidas em parafina fixadas em formalina foram inspecionadas por colora&#231;&#227;o hematoxilina&#8208;eosina&#44; corante &#225;cido peri&#243;dico de Schiff ap&#243;s digest&#227;o diast&#225;sica&#44; impregna&#231;&#227;o pela prata para reticulina e colora&#231;&#227;o de Masson em todos os casos&#46; As caracter&#237;sticas histol&#243;gicas foram registradas de acordo com o estadiamento&#44; com um sistema de pontua&#231;&#227;o semiquantitativa de quatro pontos &#40;ou seja&#44; ausente&#44; m&#237;nimo&#44; moderado e grave&#41;&#46; Os par&#226;metros inclu&#237;ram altera&#231;&#245;es arquitet&#244;nicas&#59; infiltrados portais e periportais&#59; dano celular hep&#225;tico e necrose&#44; como necrose l&#237;tica focal &#40;irregular&#41; e hepatite de interface periportal ou periseptal &#40;necrose fragmentada&#41;&#59; necrose confluente&#59; necrose em ponte e necrose submaci&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">6</span></a> Tamb&#233;m foram avaliadas outras caracter&#237;sticas&#44; como les&#227;o do ducto biliar e rea&#231;&#227;o ductular&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A terapia imunossupressora incluiu uma combina&#231;&#227;o de prednisona &#40;1&#8208;1&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#44; m&#225;ximo de 60<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#41; e azatioprina &#40;1&#8208;1&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#41;&#46; Foi feita monoterapia com prednisona sempre que houve trombocitopenia grave&#46; A dose de prednisona foi reduzida em cada visita at&#233; a dose de manuten&#231;&#227;o de 2&#44;5&#8208;5<span class="elsevierStyleHsp" style=""></span>mg ser atingida&#44; ao mesmo tempo em que mantendo par&#226;metros cl&#237;nicos e laboratoriais est&#225;veis&#46; A resposta completa e recidiva foram definidas de acordo com os crit&#233;rios do Grupo Internacional de Estudo da HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lise estat&#237;stica</span><p id="par0045" class="elsevierStylePara elsevierViewall">Foi usada a vers&#227;o 24 do SPSS para a an&#225;lise estat&#237;stica &#40;IBM SPSS Estat&#237;stica para Windows&#44; Vers&#227;o 24&#46;0&#46; NY&#44; EUA&#58;&#41;&#46; Todos os dados est&#227;o resumidos nas tabelas 1&#8208;3&#46; O teste de Kolmogorov&#8208;Smirnov foi usado para verificar a distribui&#231;&#227;o normal de dados&#46; Para verificar a exist&#234;ncia de associa&#231;&#245;es entre os grupos e todas as vari&#225;veis categ&#243;ricas&#44; foi usado a regress&#227;o log&#237;stica com a fun&#231;&#227;o de liga&#231;&#227;o <span class="elsevierStyleItalic">logit</span>&#46; Foram estimadas as raz&#245;es de chance e apresentados os respectivos intervalos de confian&#231;a de 95&#37;&#46; O teste de Mann&#8208;Whitney foi usado para comparar os dois tipos de HAI com rela&#231;&#227;o &#224;s vari&#225;veis quantitativas&#46; O n&#237;vel de signific&#226;ncia foi estabelecido em p &#8804; 0&#44;05&#46; As vari&#225;veis categ&#243;ricas foram expressas como contagens e percentuais e as vari&#225;veis cont&#237;nuas foram expressas como valores medianos &#40;m&#237;nimo&#59; m&#225;ximo&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0050" class="elsevierStylePara elsevierViewall">Dos 828 pacientes&#44; 742 &#40;89&#44;6&#37;&#41; apresentaram HAI&#8208;1 e 86 &#40;10&#44;4&#37;&#41; apresentaram HAI&#8208;2&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dados demogr&#225;ficos e cl&#237;nicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">O sexo feminino foi predominante entre os pacientes &#40;HAI&#8208;1&#58; 74&#44;9&#37;&#44; HAI&#8208;2&#58; 84&#44;9&#37;&#41;&#46; A idade m&#233;dia no in&#237;cio dos sintomas foi 111&#44;5 &#40;6&#59; 210&#41; e 53&#44;5 &#40;8&#59; 165&#41; meses para os pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;p &#60; 0&#44;001&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As crian&#231;as com achados positivos para LKM1 eram significativamente mais novas &#40;p &#60; 0&#44;001&#41;&#46; Os pacientes apresentaram um escore mediano de HAI&#44; de acordo com os Sistemas Internacionais de Classifica&#231;&#227;o da HAI de 1999 e 2008&#44; de 17 &#40;7&#59; 28&#41; e 7 &#40;2&#59; 10&#41; para HAI&#8208;1 e 15&#44;5 &#40;3&#59; 123&#41; e 6 &#40;3&#59; 9&#41; para HAI&#8208;2&#44; respectivamente&#44; revelaram uma diferen&#231;a significativa entre os grupos &#40;p &#61; 0&#44;001&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Foi observado in&#237;cio cl&#237;nico agudo em 410 &#40;56&#44;1&#37;&#41; e 50 &#40;58&#44;8&#37;&#41; pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#46; Foram observados sintomas cl&#237;nicos insidiosos em 321 &#40;43&#44;9&#37;&#41; e 35 &#40;41&#44;2&#37;&#41; crian&#231;as com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; O risco para essas duas manifesta&#231;&#245;es cl&#237;nicas n&#227;o foi significativamente diferente &#40;p &#61; 0&#44;630&#41;&#46; Foi observada insufici&#234;ncia hep&#225;tica &#40;INR de &#62; 1&#44;5&#41; em 226 &#40;30&#44;7&#37;&#41; e 31 &#40;40&#44;3&#37;&#41; pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#46; O risco de insufici&#234;ncia hep&#225;tica foi 1&#44;6 vez maior no grupo de HAI&#8208;2&#44; que foi somente marginalmente significativo &#40;p &#61; 0&#44;060&#41;&#59; 27 &#40;3&#44;6&#37;&#41; crian&#231;as com HAI&#8208;1 e nove &#40;10&#44;6&#37;&#41; crian&#231;as com HAI&#8208;2 apresentaram insufici&#234;ncia hep&#225;tica fulminante na manifesta&#231;&#227;o inicial e a diferen&#231;a foi significativa entre os grupos &#40;p &#61; 0&#44;005&#41;&#46; Al&#233;m disso&#44; o risco foi 3&#44;1 vezes maior no grupo com HAI&#8208;2&#46; Foi observado hist&#243;rico familiar de doen&#231;a autoimune&#44; inclusive diabetes&#44; doen&#231;a da tiroide&#44; doen&#231;a de Beh&#231;et e vitiligo&#44; em 161 &#40;21&#44;9&#37;&#41; pacientes com HAI&#8208;1 e 18 &#40;21&#44;2&#37;&#41; pacientes com HAI&#8208;2 &#40;p &#61; 0&#44;883&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Manifesta&#231;&#245;es autoimunes extra&#8208;hep&#225;ticas estiveram presentes em 183 &#40;24&#44;8&#37;&#41; 12 &#40;14&#44;1&#37;&#41; pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#44; com uma diferen&#231;a significativa entre os grupos &#40;p &#61; 0&#44;031&#41;&#46; O risco de manifesta&#231;&#245;es autoimunes extra&#8208;hep&#225;ticas foi duas vezes maior nos pacientes com HAI&#8208;1&#46; As doen&#231;as autoimunes associadas inclu&#237;ram l&#250;pus eritematoso sist&#234;mico&#44; paniculite de Weber&#44; diabetes tipo 1&#44; doen&#231;a da tiroide&#44; doen&#231;a cel&#237;aca&#44; doen&#231;a inflamat&#243;ria intestinal&#44; glomerulopatias e artrite&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Achados laboratoriais e radiol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Com rela&#231;&#227;o aos testes de laborat&#243;rio&#44; n&#227;o foi observada diferen&#231;a significativa entre os grupos para os n&#237;veis de bilirrubina direta no soro&#44; aminotransferase&#44; GGTP e ALP&#46; Contudo&#44; os n&#237;veis de albumina&#44; gamaglobulina e&#47;ou IgG foram significativamente maiores nos pacientes com HAI&#8208;1 do que nos com HAI&#8208;2 &#40;p &#61; 0&#44;030 e p &#60; 0&#44;001&#44; respectivamente&#41;&#59; os n&#237;veis de IgA foram menores nos pacientes com HAI&#8208;2 &#40;p &#61; 0&#44;001&#41;&#46; Foram observados n&#237;veis de C3 significativamente menores nas crian&#231;as com HAI&#8208;2 &#40;p &#61; 0&#44;032&#41; e nenhuma diferen&#231;a significativa &#40;p &#61; 0&#44;317&#41; foi observada nos n&#237;veis de C4&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Foi feita CPRM&#47;colangiografia em 309 crian&#231;as e adolescentes e os resultados foram compat&#237;veis com colangite esclerosante autoimune &#40;CEA&#41; em 60 pacientes &#40;58 com HAI&#8208;1 e dois com AIH&#8208;2&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Achados histol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Com base nos resultados das bi&#243;psias hep&#225;ticas feitas antes do tratamento imunossupressor&#44; as rosetas de hepat&#243;citos e as c&#233;lulas plasm&#225;ticas foram mais prevalentes nos pacientes com HAI&#8208;1 &#40;p &#61; 0&#44;007 e p &#60; 0&#44;001&#59; risco aumentado em 2&#44;1 vezes e 2&#44;6&#44; respectivamente&#41;&#46; Houve les&#227;o do ducto biliar em 61 pacientes&#59; fibrose em 513 pacientes e cirrose em 148 pacientes&#44; sem uma diferen&#231;a significativa entre os grupos&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Tratamentos e resultados &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Em 94&#44;1&#37; dos 828 pacientes&#44; o tratamento inicial para HAI foi uma combina&#231;&#227;o de prednisona e azatioprina&#46; Um tratamento combinado que incluiu &#225;cido ursodesoxic&#243;lico foi administrado em 30&#44;3&#37; dos pacientes&#44; micofenolato de mofetila em 3&#44;7&#37; e ciclosporina em 6&#44;3&#37;&#46; A dura&#231;&#227;o do acompanhamento foi de at&#233; 23&#44;8 anos &#40;m&#233;dia&#44; 7&#44;08 anos&#59; mediana&#44; 6&#44;4 anos&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Ap&#243;s in&#237;cio da imunossupress&#227;o&#44; a remiss&#227;o bioqu&#237;mica foi atingida em 76&#44;2&#37; de todos os pacientes &#40;HAI&#8208;1&#58; 74&#44;7&#37;&#59; HAI&#8208;2&#58; 89&#44;4&#37;&#59; p &#61; 0&#44;003&#41;&#46; O tempo mediano at&#233; a remiss&#227;o bioqu&#237;mica foi sete &#40;0&#59; 250&#41; e quatro &#40;1&#59; 149&#41; meses para HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;p &#61; 0&#44;002&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">O tratamento foi interrompido em pacientes ap&#243;s a remiss&#227;o completa&#59; 13 pacientes apresentaram recidiva p&#243;s&#8208;suspens&#227;o e retomamos o tratamento com medicamentos imunossupressores&#46; Todos os pacientes com HAI&#8208;2 que interromperam o tratamento o fizeram por sua conta ou&#44; caso por motivos m&#233;dicos&#44; antes da recomenda&#231;&#227;o de n&#227;o interrup&#231;&#227;o do tratamento&#44; que atualmente existe&#44; de acordo com o consenso internacional&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Os n&#250;meros medianos das recidivas bioqu&#237;micas foram 3 &#40;0&#59; 13&#41; e 3 &#40;0&#59; 6&#41; nos pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#44; durante o tratamento&#44; sem diferen&#231;a entre eles &#40;p &#61; 0&#44;433&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Os efeitos adversos durante o tratamento&#44; inclusive alopecia&#44; s&#237;ndrome de Cushing&#44; obesidade&#44; diabetes tipos 1 e 2&#44; embolia pulmonar&#44; estrias&#44; infec&#231;&#245;es &#40;infec&#231;&#245;es do trato urin&#225;rio e respirat&#243;rio superior&#41;&#44; pneumonia&#44; recidivas de amigdalite e meningite&#44; foram observados em 38&#44;8&#37; &#40;n &#61; 322&#41; dos pacientes&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Ficaram gr&#225;vidas 37 adolescentes &#40;4&#44;5&#37;&#41; e nenhuma delas apresentou complica&#231;&#245;es durante a gesta&#231;&#227;o ou ap&#243;s o parto&#46; Todos os beb&#234;s nasceram vivos sem complica&#231;&#245;es&#46; A azatioprina foi interrompida durante a gravidez e a dose de prednisona n&#227;o foi alterada&#46; Ap&#243;s o parto&#44; somente aquelas que amamentaram n&#227;o receberam azatioprina&#46; N&#227;o houve recidiva nas 37 pacientes&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Morbidez e mortalidade &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Foram submetidos 38 pacientes a transplante de f&#237;gado &#40;LTx&#41;&#58; 35 &#40;4&#44;7&#37;&#41; com HAI&#8208;1 e tr&#234;s &#40;3&#44;5&#37;&#41; com HAI&#8208;2&#59; 55 pacientes morreram&#58; 55 &#40;7&#44;5&#37;&#41; com HAI&#8208;1 e dois &#40;2&#44;4&#37;&#41; com HAI&#8208;2 &#40;p &#61; 0&#44;047&#41;&#46; Os &#243;bitos estavam relacionados &#224; HAI e suas comorbidades&#46; A taxa de sobrevida atuarial foi 92&#44;5&#37; e 97&#44;6&#37; nos pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#59; aos 96 meses de acompanhamento&#44; essas probabilidades foram &#8764;94&#37; e 98&#37;&#46; Aos 150 meses&#44; as probabilidades foram 86&#37; e 98&#37;&#46; No fim do acompanhamento &#40;HAI&#8208;1&#58; 278 meses&#59; HAI&#8208;2&#58; 286 meses&#41;&#44; as probabilidades de sobrevida foram &#8764;70&#37; e 90&#37;&#44; respectivamente&#46; A curva de sobrevida dos pacientes com HAI&#8208;1 foi quase igual &#224; curva de sobrevida geral&#44; pois houve somente dois &#243;bitos entre os 84 pacientes com HAI&#8208;2&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discuss&#227;o</span><p id="par0125" class="elsevierStylePara elsevierViewall">Este constitui o maior estudo cl&#237;nico de crian&#231;as e adolescentes com HAI j&#225; publicado&#46; Nesse grupo do estudo brasileiro&#44; a HAI&#8208;1 foi mais frequente&#46; Al&#233;m disso&#44; os pacientes com HAI&#8208;1 apresentaram risco mais elevado de serem submetidos a Ltx e de &#243;bito&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">O in&#237;cio mais precoce da doen&#231;a para HAI&#8208;2 neste estudo &#233; semelhante ao encontrado na literatura&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">8&#8211;10</span></a> A distribui&#231;&#227;o por sexo feminino&#47;masculino para HAI tamb&#233;m corresponde ao da literatura&#44; ou seja&#44; predomin&#226;ncia do sexo feminino&#44; principalmente entre as pacientes com HAI&#8208;1&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">As manifesta&#231;&#245;es cl&#237;nicas da HAI&#8208;1 e HAI&#8208;2 foram an&#225;logas&#44; exceto o tipo fulminante&#46; A hepatite fulminante &#233; uma manifesta&#231;&#227;o muito rara da doen&#231;a e&#44; quando ocorre&#44; est&#225; mais associada &#224; HAI&#8208;2&#46; Neste estudo&#44; a manifesta&#231;&#227;o fulminante ocorreu com mais frequ&#234;ncia na presen&#231;a da positividade anti&#8208;LKM1&#44; o que &#233; compat&#237;vel com Di Giorgio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> e outros na literura&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">10&#8211;14</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">As manifesta&#231;&#245;es extra&#8208;hep&#225;ticas associadas &#224; HAI s&#227;o vari&#225;veis em frequ&#234;ncia e preval&#234;ncia&#46; As doen&#231;as da tiroide s&#227;o descritas com mais frequ&#234;ncia&#44; semelhantemente &#224;s manifesta&#231;&#245;es extra&#8208;hep&#225;ticas relatadas no estudo de Bittencourt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">15</span></a> e Gregorio et al&#46;&#44; inclusive tireoidite&#44; vitiligo&#44; diabetes tipo 1 e doen&#231;a inflamat&#243;ria intestinal&#44; em 20&#37; das crian&#231;as com HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">13</span></a> Nossos achados s&#227;o diferentes dos de Gregorio et al&#46;&#44; que podem corresponder &#224;s diferen&#231;as regionais e &#224; susceptibilidade gen&#233;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Os escores &#40;1999 e 2008&#41; dos dois tipos de HAI foram compat&#237;veis com os de outros estudos&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">1&#44;2&#44;17</span></a> Os pacientes n&#227;o submetidos a bi&#243;psia no diagn&#243;stico atenderam aos crit&#233;rios internacionais para HAI e n&#227;o mostraram discrep&#226;ncias nos escores em nosso estudo&#46; Mileti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a> examinaram a efic&#225;cia de diagn&#243;stico do escore em crian&#231;as&#46; Inicialmente&#44; a popula&#231;&#227;o pedi&#225;trica n&#227;o foi avaliada de acordo com os crit&#233;rios de 1999&#46; Posteriormente&#44; dois estudos apresentaram resultados controversos com rela&#231;&#227;o ao uso dos dois escores&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">18&#44;19</span></a> Mileti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a> observaram alta sensibilidade e especificidade com o uso dos escores na popula&#231;&#227;o pedi&#225;trica&#59; contudo&#44; tamb&#233;m foram observadas algumas limita&#231;&#245;es&#46; A resposta terap&#234;utica continua um crit&#233;rio de diagn&#243;stico fundamental&#44; principalmente em pacientes sem marcadores de autoimunidade&#44; mesmo se eles n&#227;o atingirem um escore que indique um diagn&#243;stico definitivo de HAI&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Os n&#237;veis de albumina refor&#231;aram a gravidade da doen&#231;a&#44; principalmente em pacientes com HAI&#8208;1&#44; com pioria da fun&#231;&#227;o hep&#225;tica&#46; N&#237;veis elevados de gamaglobulina&#44; principalmente em pacientes com HAI&#8208;1&#44; s&#227;o um sinal significativo no diagn&#243;stico diferenciado entre os tipos de HAI&#46; Esse teste &#233; um importante marcador no diagn&#243;stico da HAI&#8208;1 e o resultado pode ser normal em pacientes com HAI&#8208;2&#44; o que refor&#231;a a diferen&#231;a entre os grupos&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Nenhuma diferen&#231;a ou aumentos significativos foram encontrados em nossos pacientes&#46; Esses dados diferem dos de Di Giorgio et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> que encontraram n&#237;veis elevados de IgM sem uma explica&#231;&#227;o real&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Diagnosticar colangite esclerosante continua um desafio&#46; Apesar de a detec&#231;&#227;o de les&#227;o do ducto n&#227;o indicar CEA de forma definitiva&#44; altera&#231;&#245;es histol&#243;gicas ou na CPRM compat&#237;veis com colangite esclerosante n&#227;o s&#227;o sempre observadas em pacientes afetados&#46; N&#237;veis de GGTP persistentemente elevados sugerem envolvimento do trato biliar e o acompanhamento de longo prazo ou avalia&#231;&#227;o de explante possibilita o diagn&#243;stico&#46; N&#227;o foi feita colangiografia em todos os pacientes&#46; Diversos fatores contribu&#237;ram para a dif&#237;cil execu&#231;&#227;o desse exame&#44; por exemplo necessidade de anestesia e os custos&#46; Como o estudo teve um modelo retrospectivo e n&#227;o havia recomenda&#231;&#227;o na literatura&#44; v&#225;rios servi&#231;os foram feitos somente quando o n&#237;vel de GGTP n&#227;o caiu ou quando n&#227;o houve resposta terap&#234;utica aos imunossupressores&#46; Assim&#44; pode haver um vi&#233;s neste estudo com rela&#231;&#227;o &#224; preval&#234;ncia de CEA&#44; o que faz parte dos estudos retrospectivos&#59; contudo&#44; os resultados continuam importantes&#44; devido ao grande n&#250;mero de pacientes inclu&#237;dos&#46; O Comit&#234; de Hepatologia ESPGHAN&#160;recomenda buscar s&#237;ndrome de reposi&#231;&#227;o em pacientes com HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Neste estudo&#44; alguns pacientes n&#227;o foram submetidos a bi&#243;psia hep&#225;tica devido &#224;s contraindica&#231;&#245;es&#44; como coagulopatia &#40;INR alta&#41;&#44; ascite ou trombocitopenia grave&#46; Contudo&#44; todos esses pacientes se enquadram na classifica&#231;&#227;o para HAI de acordo com os crit&#233;rios internacionais&#44; mesmo sem uma histologia de classifica&#231;&#227;o&#46; Al&#233;m disso&#44; os achados da bi&#243;psia do f&#237;gado n&#227;o foram avaliados por um &#250;nico patologista&#44; pois o estudo foi um estudo retrospectivo que coletou dados de v&#225;rios centros&#44; por&#233;m seguiu os crit&#233;rios de consenso dos patologistas brasileiros&#46; O exame do tecido hep&#225;tico antes do tratamento &#233; um importante componente de diagn&#243;stico e as diretrizes recomendam sua feitura na apresenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a> Apesar disso&#44; a necessidade de exame do tecido hep&#225;tico antes do tratamento foi contestada em crian&#231;as&#44; pois elas geralmente apresentam disfun&#231;&#227;o hep&#225;tica significativa e coagulopatia&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">22</span></a> Bjo&#776;rnsson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a> mencionaram a import&#226;ncia da histologia no diagn&#243;stico t&#237;pico de HAI e conclu&#237;ram que a maior parte dos pacientes com caracter&#237;sticas de HAO &#233; mais propensa a ter histologias hep&#225;ticas compat&#237;veis&#46; Em adultos&#44; a presen&#231;a de cirrose no quadro cl&#237;nico inicial claramente piora a doen&#231;a&#44; leva a uma taxa de sobrevida de 10 anos de &#8764;60&#37; em compara&#231;&#227;o com 80&#37; dos pacientes sem cirrose&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a> Contudo&#44; Radhakrishnan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">24</span></a> observaram que a presen&#231;a de cirrose n&#227;o afeta a sobrevida de longo prazo em crian&#231;as&#46; A cirrose foi o achado predominante na manifesta&#231;&#227;o inicial dos dois tipos de HAI&#59; contudo&#44; essa observa&#231;&#227;o difere dos dados obtidos por Gregorio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a> e Saadah et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">25</span></a> que relataram uma preval&#234;ncia de cirrose de 69&#37; e 38&#37; entre os pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#46; No estudo atual&#44; foram observadas diferen&#231;as nos resultados histopatol&#243;gicos do f&#237;gado entre os grupos de HAI&#44; com uma maior preval&#234;ncia de rosetas e c&#233;lulas plasm&#225;ticas em pacientes com HAI&#8208;1&#44; o que n&#227;o foi relatado na literatura&#46; A presen&#231;a de cirrose na primeira manifesta&#231;&#227;o da doen&#231;a mostra a gravidade da HAI&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">A resposta terap&#234;utica &#233; um dos melhores par&#226;metros para determinar se o perfil cl&#237;nico da hepatite pode ser atribu&#237;do a uma causa imunol&#243;gica&#46; A remiss&#227;o da doen&#231;a &#233; sempre o principal objetivo do tratamento imunossupressor&#46; Em geral&#44; a resposta terap&#234;utica &#233; mais de 70&#37; em pacientes com HAI&#8208;1 e 85&#37; nos com HAI&#8208;2&#44;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">16&#44;26</span></a> semelhante aos achados neste estudo&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Este estudo revelou um tempo reduzido de remiss&#227;o nos pacientes com HAI&#8208;2&#46; Esse achado &#233; incompat&#237;vel com os de Gregorio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Uma preocupa&#231;&#227;o importante s&#227;o os comportamentos de n&#227;o ades&#227;o ao tratamento&#44; principalmente entre adolescentes&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">13</span></a> Neste estudo&#44; o tratamento foi interrompido nos dois grupos pelo m&#233;dico e o tratamento tamb&#233;m foi interrompido em alguns pacientes devido &#224; n&#227;o ades&#227;o&#46; Ferreira et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">14</span></a> estudaram crian&#231;as que atingiram remiss&#227;o cl&#237;nica&#8208;laboratorial ap&#243;s imunossupress&#227;o por 24 meses e observaram uma indec&#234;ncia de 54&#44;5&#37; de recidiva da doen&#231;a ap&#243;s o tratamento&#44; mesmo na presen&#231;a de remiss&#227;o histol&#243;gica&#46; Eles n&#227;o identificaram os fatores preditivos associados &#224; recidiva&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">LTx &#233; necess&#225;rio para tratamento de HAI em &#8764;10&#37; dos casos<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">26&#44;27</span></a> e foi feito em 10&#37; dos pacientes pedi&#225;tricos com HAI e 23&#37; dos pacientes com colangite esclerosante&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">26</span></a> Neste estudo&#44; foi feito transplante em 4&#44;7&#37; e 3&#44;5&#37; dos pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#44; indicou&#8208;se que a doen&#231;a foi bem controlada com imunossupressores&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Os fatores de limita&#231;&#227;o deste estudo incluem o fato de ele ser retrospectivo e&#44; consequentemente&#44; haver a possibilidade de vieses e dados incompletos de alguns pacientes&#59; contudo&#44; &#233; importante notar que ele incluiu pacientes de v&#225;rios centros secund&#225;rios e terci&#225;rios de refer&#234;ncia e constitui o maior estudo de crian&#231;as e adolescentes com HAI j&#225; publicado&#46; Os dados apresentados n&#227;o representam a preval&#234;ncia real dos pacientes pedi&#225;tricos com hepatite autoimune no Brasil&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Em resumo&#44; neste grande estudo cl&#237;nico de crian&#231;as e adolescentes brasileiros com HAI&#58; a HAI&#8208;1 foi mais frequente&#59; a HAI&#8208;2 afetou crian&#231;as mais novas&#44; apresentou taxas de remiss&#227;o mais elevadas e se manifestou mais precocemente que a HAI&#8208;1&#59; e os pacientes com HAI&#8208;1 apresentaram maior risco de serem submetidos a LTx e &#243;bito&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflitos de interesse</span><p id="par0200" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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              "titulo" => "Achados laboratoriais e radiol&#243;gicos &#40;tabela 2&#41;"
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            0 => "Autoimmune hepatitis"
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          "palabras" => array:6 [
            0 => "Hepatite autoimune"
            1 => "Cl&#237;nico"
            2 => "Laboratorial"
            3 => "Tratamentos"
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            5 => "Brasil"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This large study with a long&#8208;term follow&#8208;up aimed to evaluate the clinical presentation&#44; laboratory findings&#44; histological profile&#44; treatments&#44; and outcomes of children and adolescents with autoimmune hepatitis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed&#46; A questionnaire was used to collect anonymous data on clinical presentation&#44; biochemical and histological findings&#44; and treatments&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Of all patients&#44; 89&#46;6&#37; had autoimmune hepatitis&#8208;1 and 10&#46;4&#37; had autoimmune hepatitis&#8208;2&#46; The female sex was predominant in both groups&#46; The median age at symptom onset was 111&#46;5 &#40;6&#59; 210&#41; and 53&#46;5 &#40;8&#59; 165&#41; months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis&#8208;2&#44; respectively&#46; Acute clinical onset was observed in 56&#46;1&#37; and 58&#46;8&#37; and insidious symptoms in 43&#46;9&#37; and 41&#46;2&#37; of the patients with autoimmune hepatitis&#8208;1 and autoimmune hepatitis&#8208;2&#44; respectively&#46; The risk of hepatic failure was 1&#46;6&#8208;fold higher for autoimmune hepatitis&#8208;2&#46; Fulminant hepatic failure occurred in 3&#46;6&#37; and 10&#46;6&#37; of the patients with autoimmune hepatitis&#8208;1 and autoimmune hepatitis&#8208;2&#44; respectively&#59; the risk was 3&#46;1&#8208;fold higher for autoimmune hepatitis&#8208;2&#46; The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis&#8208;1&#44; while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis&#8208;2&#46; Cirrhosis was observed in 22&#46;4&#37; of the patients&#59; biochemical remission was achieved in 76&#46;2&#37;&#46; The actuarial survival rate was 93&#46;0&#37;&#46; A total of 4&#46;6&#37; underwent liver transplantation&#44; and 6&#46;9&#37; died &#40;autoimmune hepatitis&#8208;1&#58; 7&#46;5&#37;&#59; autoimmune hepatitis&#8208;2&#58; 2&#46;4&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In this large clinical series of Brazilian children and adolescents&#44; autoimmune hepatitis&#8208;1 was more frequent&#44; and patients with autoimmune hepatitis&#8208;2 exhibited higher disease remission rates with earlier response to treatment&#46; Patients with autoimmune hepatitis&#8208;1 had a higher risk of death&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Este estudo com acompanhamento de longo prazo visou a avaliar o quadro cl&#237;nico&#44; os achados laboratoriais&#44; o perfil histol&#243;gico&#44; os tratamentos e os resultados de crian&#231;as e adolescentes com hepatite autoimune&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foram analisados os prontu&#225;rios m&#233;dicos de 828 crian&#231;as e adolescentes com HAI&#46; Foi usado um question&#225;rio para coletar os dados an&#244;nimos sobre o quadro cl&#237;nico&#44; os achados bioqu&#237;micos e histol&#243;gicos e os tratamentos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De todos os pacientes&#44; 89&#44;6&#37; tinham hepatite autoimune&#8208;1 e 10&#44;4&#37; hepatite autoimune&#8208;2&#46; O sexo feminino foi predominante nos dois grupos&#46; A idade m&#233;dia no in&#237;cio dos sintomas foi 111&#44;5 &#40;6&#59; 210&#41; e 53&#44;5 &#40;8&#59; 165&#41; meses nos pacientes com hepatite autoimune&#8208;1 e hepatite autoimune&#8208;2&#44; respectivamente&#46; Foi observado in&#237;cio cl&#237;nico agudo em 56&#44;1&#37; e 58&#44;8&#37; e sintomas insidiosos em 43&#44;9&#37; e 41&#44;2&#37; dos pacientes com hepatite autoimune&#8208;1 e hepatite autoimune&#8208;2&#44; respectivamente&#46; A probabilidade de insufici&#234;ncia hep&#225;tica foi 1&#44;6 vezes maior para hepatite autoimune&#8208;2&#59; 3&#44;6&#37; e 10&#44;6&#37; dos pacientes com hepatite autoimune&#8208;1 e hepatite autoimune&#8208;2&#44; respectivamente&#44; apresentaram insufici&#234;ncia hep&#225;tica fulminante&#59; o risco foi 3&#44;1 vezes maior para hepatite autoimune&#8208;2&#46; Os n&#237;veis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune&#8208;1&#44; ao passo que os n&#237;veis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune&#8208;2&#59; 22&#44;4&#37; dos pacientes apresentaram cirrose e a remiss&#227;o bioqu&#237;mica foi atingida em 76&#44;2&#37;&#46; A taxa de sobrevida atuarial foi de 93&#44;0&#37;&#46; Um total de 4&#44;6&#37; pacientes foram submetidos a transplante de f&#237;gado e 6&#44;9&#37; morreram &#40;hepatite autoimune&#8208;1&#58; 7&#44;5&#37;&#59; hepatite autoimune&#8208;2&#58; 2&#44;4&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nesta grande s&#233;rie cl&#237;nica de crian&#231;as e adolescentes brasileiros&#44; a hepatite autoimune&#8208;1 foi mais frequente e os pacientes com hepatite autoimune&#8208;2 mostraram maiores taxas de remiss&#227;o da doen&#231;a com respostas mais r&#225;pidas aos tratamentos&#46; Os pacientes com hepatite autoimune&#8208;1 apresentaram maior risco de &#243;bito&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Como citar este artigo&#58; Porta G&#44; Carvalho E&#44; Santos JL&#44; Gama J&#44; Borges CV&#44; Seixas RB&#44; et al&#46; Autoimmune hepatitis in 828 Brazilian children and adolescents&#58; clinical and laboratory findings&#44; histological profile&#44; treatments&#44; and outcomes&#46; J Pediatr &#40;Rio J&#41;&#46; 2019&#59;95&#58;419&#8211;27&#46;</p>"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">M&#233;todo de Kaplan&#8208;Meier para analisar a sobrevida de pacientes com hepatite autoimune&#46; A sobrevida &#233; significativamente maior nos pacientes com HAI tipo 2&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">DP&#44; desvio&#8208;padr&#227;o&#59; HAI&#44; hepatite autoimune&#59; IC&#44; intervalo de confian&#231;a&#59; m&#225;x&#46;&#44; m&#225;ximo&#59; min&#46;&#44; m&#237;nimo&#59; RC&#44; raz&#227;o de chance&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HAI&#8208;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">RCHAI&#8208;1&#47;HAI&#8208;2&#40;IC de 95&#37;&#41;&#59;Regress&#227;o log&#237;stica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade no in&#237;cio &#40;meses&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;m&#237;n&#46;&#8208;m&#225;x&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">111&#44;5 &#40;6&#59; 210&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#44;5 &#40;8&#59; 165&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Idade no diagn&#243;stico &#40;meses&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;m&#237;n&#46;&#8208;m&#225;x&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">122&#44;5 &#40;6&#59; 219&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#44;0 &#40;12&#59; 200&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186 &#40;25&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;15&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;88 &#40;1&#44;02&#44; 3&#44;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;044<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">556 &#40;74&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73 &#40;84&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Quadro cl&#237;nico</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Agudo&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">410 &#40;56&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;58&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;11 &#40;0&#44;71&#44; 1&#44;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;630<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Insidiosos&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">321 &#40;43&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;41&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;005<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fulminante</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;3&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;10&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;32 &#40;0&#44;14&#44; 0&#44;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&#44; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">715 &#40;96&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76 &#40;89&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Insufici&#234;ncia hep&#225;tica</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>INR &#62; 1&#44;5 n &#40;&#37;&#41;&#44; n&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">226 &#40;30&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;40&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;060<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Manifesta&#231;&#245;es extra&#8208;hep&#225;ticas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">183 &#40;24&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;14&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;01 &#40;1&#44;07&#44; 3&#44;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;031<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Gamaglobulinemia &#40;g&#47;dL&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">34 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Colangiografia &#40;colangite esclerosante&#41; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim &#8211; N &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">559 &#40;93&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">61 &#40;88&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 &#40;6&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;11&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">485 &#40;83&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">52 &#40;77&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">112 &#40;17&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;22&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">310 &#40;52&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">24 &#40;35&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">276 &#40;47&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">315 &#40;53&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">21 &#40;30&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">274 &#40;46&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;69&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">461 &#40;77&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;636<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">131 &#40;22&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17 &#40;24&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">56 &#40;9&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">539 &#40;90&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">62 &#40;92&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;m&#237;n&#46;&#8208;m&#225;x&#46;&#41;&nbsp;\t\t\t\t\t\t\n
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Artigo Original
Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes
Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados
Gilda Portaa,
Autor para correspondência
gildaporta@gmail.com

Autor para correspondência.
, Elisa de Carvalhob, Jorge L. Santosc, Jorge Gamad, Cristian V. Borgesa, Renata B.P.M. Seixase, Alexandre R. Ferreiraf, Irene K. Miuraa, Themis R. Silveirag, Luciana R. Silvah, Eleonora D.T. Fagundesf, Maria A. Bellomo‐Brandaoi, Regina Sawamuraj, Sandra M. Vieirak, Melina U. Melereg, Cibele D.F. Marquesh, Renata P. Pugliesea, Vera L. Danesia, Adriana Portaa, Marise E. Marsillacl,m..., Marcia A. Valladaresn, Daniela G. Menezeso, Carlos Kielingk, Mariana N. de Paulap, Juliana R. Vasconcelosq, Cristina T. Ferreirag, Nilza Perinr, Leonardo R. Resendes, Jussara Maiat, Adriana M.A. De Tommasoi, Gabriel HesseliVer más
a Hospital Sírio Libanês, Hospital Menino Jesus, Grupo de Hepatologia e Transplante Pediátrico, São Paulo, SP, Brasil
b Hospital de Base do Distrito Federal, Hospital da Criança de Brasília, Departamento de Gastroenterologia e Hepatologia, Brasília, DF, Brasil
c Universidade da Beira Interior, Faculdade de Ciências da Saúde, Centro de Pesquisa em Ciências da Saúde (CICS‐UBI), Covilhã, Portugal
d Universidade da Beira Interior, Centro de Matemática e Aplicações, Departamento de Matemática, Covilhã, Portugal
e Hospital de Base do Distrito Federal, Hospital da Criança de Brasília, Departamento de Gastroenterologia Pediátrica, Brasília, DF, Brasil
f Universidade Federal de Minas Gerais (UFMG), Departamento de Gastroenterologia e Hepatologia Pediátrica, Belo Horizonte, MG, Brasil
g Hospital Santo Antônio, Departamento de Gastroenterologia e Hepatologia Pediátrica, Porto Alegre, RS, Brasil
h Universidade Federal da Bahia (UFBA), Departamento de Gastroenterologia e Hepatologia Pediátrica, Salvador, BA, Brasil
i Universidade Estadual de Campinas (Unicamp), Departamento de Gastroenterologia e Hepatologia Pediátrica, Campinas, SP, Brasil
j Universidade de São Paulo (USP), Faculdade de Medicina de Ribeirão Preto (FMRP), Departamento de Gastroenterologia e Hepatologia Pediátrica, Ribeirão Preto, SP, Brasil
k Universidade Federal do Rio Grande do Sul (UFRGS), Unidade de Transplante de Fígado, Porto Alegre, RS, Brasil
l Universidade do Estado do Rio de Janeiro (UERJ), Departamento de Gastroenterologia Pediátrica, Rio de Janeiro, RJ, Brasil
m Hospital Federal dos Servidores do Estado, Rio de Janeiro, RJ, Brasil
n Universidade Federal do Rio de Janeiro (UFRJ), Departamento de Gastroenterologia e Hepatologia Pediátrica, Rio de Janeiro, RJ, Brasil
o Universidade Federal de Sergipe (UFS), Departamento de Gastroenterologia e Hepatologia Pediátrica, São Cristóvão, SE, Brasil
p Irmandade da Santa Casa Misericórdia de São Paulo, Departamento de Gastroenterologia e Hepatologia Pediátrica, São Paulo, SP, Brasil
q Universidade Federal da Paraíba (UFPB), Departamento de Gastroenterologia e Hepatologia Pediátrica, João Pessoa, PB, Brasil
r Hospital Infantil Joana de Gusmão, Departamento de Gastroenterologia e Hepatologia Pediátrica, Florianópolis, SC, Brasil
s Universidade Federal de Mato Grosso do Sul (UFMS), Departamento de Gastroenterologia Pediátrica, Campo Grande, MS, Brasil
t Universidade Federal do Rio Grande do Norte (UFRN), Departamento de Gastroenterologia e Hepatologia Pediátrica, Natal, RN, Brasil
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        "titulo" => "Hepatite autoimune em 828 crian&#231;as e adolescentes brasileiros&#58; achados cl&#237;nicos e laboratoriais&#44; perfil histol&#243;gico&#44; tratamentos e resultados"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">M&#233;todo de Kaplan&#8208;Meier para analisar a sobrevida de pacientes com hepatite autoimune&#46; A sobrevida &#233; significativamente maior nos pacientes com HAI tipo 2&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A hepatite autoimune &#40;HAI&#41; &#233; uma doen&#231;a hep&#225;tica cr&#244;nica normalmente progressiva e caracterizada histologicamente por inflama&#231;&#227;o periportal&#44; necrose em ponte&#44; forma&#231;&#227;o de rosetas &#40;<span class="elsevierStyleItalic">rosetting</span>&#41; nas c&#233;lulas hep&#225;ticas e infiltra&#231;&#227;o de c&#233;lulas plasm&#225;ticas&#46; Apesar de a etiologia ser desconhecida&#44; sua patog&#234;nese tem com base&#44; no m&#237;nimo parcialmente&#44; a autorreatividade aberrante&#46; O fen&#243;tipo cl&#225;ssico foi caracterizado por alguns marcadores sorol&#243;gicos&#44; principalmente anticorpos antinucleares&#44; anticorpos do m&#250;sculo liso &#40;SMAs&#41; e anticorpos contra a fra&#231;&#227;o microssomal de f&#237;gado e rim tipo 1 &#40;anti&#8208;LKM1s&#41;&#44; independentemente da associa&#231;&#227;o com os anticorpos anticitosol hep&#225;tico tipo 1&#44; hipergamaglobulinemia&#44; aumento nos n&#237;veis de imunoglobulina no soro &#40;Ig&#41;G&#44; hepatite de interface no exame histol&#243;gico e resposta &#224; terapia com corticosteroides&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">1&#8211;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Foram publicados estudos sobre a epidemiologia e o hist&#243;rico natural da HAI pedi&#225;trica&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">4&#44;5</span></a> o que &#233; importante&#44; considerando que a maior parte do conhecimento sobre HAI prov&#233;m de estudos em adultos&#46; Os estudos limitados em crian&#231;as demonstraram as peculiaridades dessa doen&#231;a em pacientes pedi&#225;tricos&#46; Visamos a avaliar o quadro cl&#237;nico&#44; os achados laboratoriais&#44; o perfil histol&#243;gico&#44; os tratamentos e os resultados de crian&#231;as e adolescentes com HAI na Am&#233;rica do Sul em um grande estudo com acompanhamento de longo prazo&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Este estudo multic&#234;ntrico retrospectivo&#160;foi feito para avaliar os resultados cl&#237;nicos de 828 crian&#231;as e adolescentes com hist&#243;rico de HAI bem documentado e de longo prazo de acordo com os crit&#233;rios do Grupo Internacional de Estudo da HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a> Os dados foram coletados de relat&#243;rios de centros &#250;nicos&#46; Um question&#225;rio avaliou os dados an&#244;nimos sobre as caracter&#237;sticas demogr&#225;ficas&#44; o quadro cl&#237;nico&#44; os achados bioqu&#237;micos e histol&#243;gicos e os tratamentos&#46; Os pacientes foram acompanhados de 1983 a 2015 em 17 centros de gastroenterologia&#47;hepatologia pedi&#225;trica em todo o Brasil&#46; Este estudo foi aprovado pelos comit&#234;s de &#233;tica relacionados &#40;n&#250;mero CAAE 53562116&#46;5&#46;1001&#46;0068&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Todas as crian&#231;as e adolescentes foram submetidas a um protocolo cl&#237;nico e laboratorial&#44; inclusive avalia&#231;&#227;o dos par&#226;metros bioqu&#237;micos&#44; como alanina aminotransferase&#44; aspartato aminotransferase&#44; gamaglutamiltranspeptidase &#40;GGTP&#41;&#44; fosfatase alcalina &#40;ALP&#41;&#44; albumina&#44; gamaglobulina&#44; raz&#227;o normalizada internacional &#40;INR&#41;&#44; bilirrubina total e direta &#40;DB&#41;&#44; glicose s&#233;rica&#44; triiodotironina&#44; tiroxina e horm&#244;nio estimulante da tireoide medidos com radioimunoensaio&#46; Os n&#237;veis s&#233;ricos de Ig e complementos foram medidos com nefelometria&#44; que foram expressos em g&#47;L e variaram por centro&#46; Os resultados foram registrados como normal&#44; aumentado ou reduzido&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Todos os pacientes foram examinados na apresenta&#231;&#227;o para anticorpos antinucleares&#44; anti&#8208;SMA&#44; anti&#8208;LKM1 e antimitoc&#244;ndria&#46; As amostras de soro foram tituladas at&#233; 1&#47;320&#46; Os t&#237;tulos &#62; 1&#58;40 e 1&#47;20 foram considerados positivos para anti&#8208;SMA e anti&#8208;LKM1&#44; respectivamente&#46; Al&#233;m disso&#44; os pacientes apresentaram achados negativos para o v&#237;rus da hepatite A&#44; B e C&#44; v&#237;rus da imunodefici&#234;ncia humana&#44; citomegalov&#237;rus e v&#237;rus Epstein&#8208;Barr&#46; Eles n&#227;o apresentaram hist&#243;rico de uso de drogas ou &#225;lcool nem exposi&#231;&#227;o a medicamentos hepatot&#243;xicos&#46; Foram exclu&#237;dos os pacientes com defici&#234;ncia de alfa&#8208;1 antitripsina e doen&#231;a de Wilson&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O exame de colangiografia foi feito por colangiopancreatografia por resson&#226;ncia magn&#233;tica &#40;CPRM&#41; ou por endoscopia em pacientes que n&#227;o responderam aos medicamentos imunossupressores ou apresentaram n&#237;veis aumentos de GGTP durante o monitoramento da doen&#231;a&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Foi feita bi&#243;psia hep&#225;tica em 664 &#40;80&#44;2&#37;&#41; pacientes antes do tratamento imunossupressor&#44; por meio de bi&#243;psia por agulha percut&#226;nea com uma agulha Tru&#8208;Cut ou cirurgia&#59; 253 crian&#231;as foram submetidas a mais de uma bi&#243;psia durante o acompanhamento para documentar reca&#237;das ou como um crit&#233;rio de interrup&#231;&#227;o da terapia por dois anos&#44; em casos de remiss&#245;es cl&#237;nicas e bioqu&#237;micas&#46; As se&#231;&#245;es embebidas em parafina fixadas em formalina foram inspecionadas por colora&#231;&#227;o hematoxilina&#8208;eosina&#44; corante &#225;cido peri&#243;dico de Schiff ap&#243;s digest&#227;o diast&#225;sica&#44; impregna&#231;&#227;o pela prata para reticulina e colora&#231;&#227;o de Masson em todos os casos&#46; As caracter&#237;sticas histol&#243;gicas foram registradas de acordo com o estadiamento&#44; com um sistema de pontua&#231;&#227;o semiquantitativa de quatro pontos &#40;ou seja&#44; ausente&#44; m&#237;nimo&#44; moderado e grave&#41;&#46; Os par&#226;metros inclu&#237;ram altera&#231;&#245;es arquitet&#244;nicas&#59; infiltrados portais e periportais&#59; dano celular hep&#225;tico e necrose&#44; como necrose l&#237;tica focal &#40;irregular&#41; e hepatite de interface periportal ou periseptal &#40;necrose fragmentada&#41;&#59; necrose confluente&#59; necrose em ponte e necrose submaci&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">6</span></a> Tamb&#233;m foram avaliadas outras caracter&#237;sticas&#44; como les&#227;o do ducto biliar e rea&#231;&#227;o ductular&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A terapia imunossupressora incluiu uma combina&#231;&#227;o de prednisona &#40;1&#8208;1&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#44; m&#225;ximo de 60<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#41; e azatioprina &#40;1&#8208;1&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#41;&#46; Foi feita monoterapia com prednisona sempre que houve trombocitopenia grave&#46; A dose de prednisona foi reduzida em cada visita at&#233; a dose de manuten&#231;&#227;o de 2&#44;5&#8208;5<span class="elsevierStyleHsp" style=""></span>mg ser atingida&#44; ao mesmo tempo em que mantendo par&#226;metros cl&#237;nicos e laboratoriais est&#225;veis&#46; A resposta completa e recidiva foram definidas de acordo com os crit&#233;rios do Grupo Internacional de Estudo da HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">1</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lise estat&#237;stica</span><p id="par0045" class="elsevierStylePara elsevierViewall">Foi usada a vers&#227;o 24 do SPSS para a an&#225;lise estat&#237;stica &#40;IBM SPSS Estat&#237;stica para Windows&#44; Vers&#227;o 24&#46;0&#46; NY&#44; EUA&#58;&#41;&#46; Todos os dados est&#227;o resumidos nas tabelas 1&#8208;3&#46; O teste de Kolmogorov&#8208;Smirnov foi usado para verificar a distribui&#231;&#227;o normal de dados&#46; Para verificar a exist&#234;ncia de associa&#231;&#245;es entre os grupos e todas as vari&#225;veis categ&#243;ricas&#44; foi usado a regress&#227;o log&#237;stica com a fun&#231;&#227;o de liga&#231;&#227;o <span class="elsevierStyleItalic">logit</span>&#46; Foram estimadas as raz&#245;es de chance e apresentados os respectivos intervalos de confian&#231;a de 95&#37;&#46; O teste de Mann&#8208;Whitney foi usado para comparar os dois tipos de HAI com rela&#231;&#227;o &#224;s vari&#225;veis quantitativas&#46; O n&#237;vel de signific&#226;ncia foi estabelecido em p &#8804; 0&#44;05&#46; As vari&#225;veis categ&#243;ricas foram expressas como contagens e percentuais e as vari&#225;veis cont&#237;nuas foram expressas como valores medianos &#40;m&#237;nimo&#59; m&#225;ximo&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0050" class="elsevierStylePara elsevierViewall">Dos 828 pacientes&#44; 742 &#40;89&#44;6&#37;&#41; apresentaram HAI&#8208;1 e 86 &#40;10&#44;4&#37;&#41; apresentaram HAI&#8208;2&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dados demogr&#225;ficos e cl&#237;nicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">O sexo feminino foi predominante entre os pacientes &#40;HAI&#8208;1&#58; 74&#44;9&#37;&#44; HAI&#8208;2&#58; 84&#44;9&#37;&#41;&#46; A idade m&#233;dia no in&#237;cio dos sintomas foi 111&#44;5 &#40;6&#59; 210&#41; e 53&#44;5 &#40;8&#59; 165&#41; meses para os pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;p &#60; 0&#44;001&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As crian&#231;as com achados positivos para LKM1 eram significativamente mais novas &#40;p &#60; 0&#44;001&#41;&#46; Os pacientes apresentaram um escore mediano de HAI&#44; de acordo com os Sistemas Internacionais de Classifica&#231;&#227;o da HAI de 1999 e 2008&#44; de 17 &#40;7&#59; 28&#41; e 7 &#40;2&#59; 10&#41; para HAI&#8208;1 e 15&#44;5 &#40;3&#59; 123&#41; e 6 &#40;3&#59; 9&#41; para HAI&#8208;2&#44; respectivamente&#44; revelaram uma diferen&#231;a significativa entre os grupos &#40;p &#61; 0&#44;001&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Foi observado in&#237;cio cl&#237;nico agudo em 410 &#40;56&#44;1&#37;&#41; e 50 &#40;58&#44;8&#37;&#41; pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#46; Foram observados sintomas cl&#237;nicos insidiosos em 321 &#40;43&#44;9&#37;&#41; e 35 &#40;41&#44;2&#37;&#41; crian&#231;as com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; O risco para essas duas manifesta&#231;&#245;es cl&#237;nicas n&#227;o foi significativamente diferente &#40;p &#61; 0&#44;630&#41;&#46; Foi observada insufici&#234;ncia hep&#225;tica &#40;INR de &#62; 1&#44;5&#41; em 226 &#40;30&#44;7&#37;&#41; e 31 &#40;40&#44;3&#37;&#41; pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#46; O risco de insufici&#234;ncia hep&#225;tica foi 1&#44;6 vez maior no grupo de HAI&#8208;2&#44; que foi somente marginalmente significativo &#40;p &#61; 0&#44;060&#41;&#59; 27 &#40;3&#44;6&#37;&#41; crian&#231;as com HAI&#8208;1 e nove &#40;10&#44;6&#37;&#41; crian&#231;as com HAI&#8208;2 apresentaram insufici&#234;ncia hep&#225;tica fulminante na manifesta&#231;&#227;o inicial e a diferen&#231;a foi significativa entre os grupos &#40;p &#61; 0&#44;005&#41;&#46; Al&#233;m disso&#44; o risco foi 3&#44;1 vezes maior no grupo com HAI&#8208;2&#46; Foi observado hist&#243;rico familiar de doen&#231;a autoimune&#44; inclusive diabetes&#44; doen&#231;a da tiroide&#44; doen&#231;a de Beh&#231;et e vitiligo&#44; em 161 &#40;21&#44;9&#37;&#41; pacientes com HAI&#8208;1 e 18 &#40;21&#44;2&#37;&#41; pacientes com HAI&#8208;2 &#40;p &#61; 0&#44;883&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Manifesta&#231;&#245;es autoimunes extra&#8208;hep&#225;ticas estiveram presentes em 183 &#40;24&#44;8&#37;&#41; 12 &#40;14&#44;1&#37;&#41; pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#44; com uma diferen&#231;a significativa entre os grupos &#40;p &#61; 0&#44;031&#41;&#46; O risco de manifesta&#231;&#245;es autoimunes extra&#8208;hep&#225;ticas foi duas vezes maior nos pacientes com HAI&#8208;1&#46; As doen&#231;as autoimunes associadas inclu&#237;ram l&#250;pus eritematoso sist&#234;mico&#44; paniculite de Weber&#44; diabetes tipo 1&#44; doen&#231;a da tiroide&#44; doen&#231;a cel&#237;aca&#44; doen&#231;a inflamat&#243;ria intestinal&#44; glomerulopatias e artrite&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Achados laboratoriais e radiol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Com rela&#231;&#227;o aos testes de laborat&#243;rio&#44; n&#227;o foi observada diferen&#231;a significativa entre os grupos para os n&#237;veis de bilirrubina direta no soro&#44; aminotransferase&#44; GGTP e ALP&#46; Contudo&#44; os n&#237;veis de albumina&#44; gamaglobulina e&#47;ou IgG foram significativamente maiores nos pacientes com HAI&#8208;1 do que nos com HAI&#8208;2 &#40;p &#61; 0&#44;030 e p &#60; 0&#44;001&#44; respectivamente&#41;&#59; os n&#237;veis de IgA foram menores nos pacientes com HAI&#8208;2 &#40;p &#61; 0&#44;001&#41;&#46; Foram observados n&#237;veis de C3 significativamente menores nas crian&#231;as com HAI&#8208;2 &#40;p &#61; 0&#44;032&#41; e nenhuma diferen&#231;a significativa &#40;p &#61; 0&#44;317&#41; foi observada nos n&#237;veis de C4&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Foi feita CPRM&#47;colangiografia em 309 crian&#231;as e adolescentes e os resultados foram compat&#237;veis com colangite esclerosante autoimune &#40;CEA&#41; em 60 pacientes &#40;58 com HAI&#8208;1 e dois com AIH&#8208;2&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Achados histol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Com base nos resultados das bi&#243;psias hep&#225;ticas feitas antes do tratamento imunossupressor&#44; as rosetas de hepat&#243;citos e as c&#233;lulas plasm&#225;ticas foram mais prevalentes nos pacientes com HAI&#8208;1 &#40;p &#61; 0&#44;007 e p &#60; 0&#44;001&#59; risco aumentado em 2&#44;1 vezes e 2&#44;6&#44; respectivamente&#41;&#46; Houve les&#227;o do ducto biliar em 61 pacientes&#59; fibrose em 513 pacientes e cirrose em 148 pacientes&#44; sem uma diferen&#231;a significativa entre os grupos&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Tratamentos e resultados &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Em 94&#44;1&#37; dos 828 pacientes&#44; o tratamento inicial para HAI foi uma combina&#231;&#227;o de prednisona e azatioprina&#46; Um tratamento combinado que incluiu &#225;cido ursodesoxic&#243;lico foi administrado em 30&#44;3&#37; dos pacientes&#44; micofenolato de mofetila em 3&#44;7&#37; e ciclosporina em 6&#44;3&#37;&#46; A dura&#231;&#227;o do acompanhamento foi de at&#233; 23&#44;8 anos &#40;m&#233;dia&#44; 7&#44;08 anos&#59; mediana&#44; 6&#44;4 anos&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Ap&#243;s in&#237;cio da imunossupress&#227;o&#44; a remiss&#227;o bioqu&#237;mica foi atingida em 76&#44;2&#37; de todos os pacientes &#40;HAI&#8208;1&#58; 74&#44;7&#37;&#59; HAI&#8208;2&#58; 89&#44;4&#37;&#59; p &#61; 0&#44;003&#41;&#46; O tempo mediano at&#233; a remiss&#227;o bioqu&#237;mica foi sete &#40;0&#59; 250&#41; e quatro &#40;1&#59; 149&#41; meses para HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;p &#61; 0&#44;002&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">O tratamento foi interrompido em pacientes ap&#243;s a remiss&#227;o completa&#59; 13 pacientes apresentaram recidiva p&#243;s&#8208;suspens&#227;o e retomamos o tratamento com medicamentos imunossupressores&#46; Todos os pacientes com HAI&#8208;2 que interromperam o tratamento o fizeram por sua conta ou&#44; caso por motivos m&#233;dicos&#44; antes da recomenda&#231;&#227;o de n&#227;o interrup&#231;&#227;o do tratamento&#44; que atualmente existe&#44; de acordo com o consenso internacional&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Os n&#250;meros medianos das recidivas bioqu&#237;micas foram 3 &#40;0&#59; 13&#41; e 3 &#40;0&#59; 6&#41; nos pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#44; durante o tratamento&#44; sem diferen&#231;a entre eles &#40;p &#61; 0&#44;433&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Os efeitos adversos durante o tratamento&#44; inclusive alopecia&#44; s&#237;ndrome de Cushing&#44; obesidade&#44; diabetes tipos 1 e 2&#44; embolia pulmonar&#44; estrias&#44; infec&#231;&#245;es &#40;infec&#231;&#245;es do trato urin&#225;rio e respirat&#243;rio superior&#41;&#44; pneumonia&#44; recidivas de amigdalite e meningite&#44; foram observados em 38&#44;8&#37; &#40;n &#61; 322&#41; dos pacientes&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Ficaram gr&#225;vidas 37 adolescentes &#40;4&#44;5&#37;&#41; e nenhuma delas apresentou complica&#231;&#245;es durante a gesta&#231;&#227;o ou ap&#243;s o parto&#46; Todos os beb&#234;s nasceram vivos sem complica&#231;&#245;es&#46; A azatioprina foi interrompida durante a gravidez e a dose de prednisona n&#227;o foi alterada&#46; Ap&#243;s o parto&#44; somente aquelas que amamentaram n&#227;o receberam azatioprina&#46; N&#227;o houve recidiva nas 37 pacientes&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Morbidez e mortalidade &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Foram submetidos 38 pacientes a transplante de f&#237;gado &#40;LTx&#41;&#58; 35 &#40;4&#44;7&#37;&#41; com HAI&#8208;1 e tr&#234;s &#40;3&#44;5&#37;&#41; com HAI&#8208;2&#59; 55 pacientes morreram&#58; 55 &#40;7&#44;5&#37;&#41; com HAI&#8208;1 e dois &#40;2&#44;4&#37;&#41; com HAI&#8208;2 &#40;p &#61; 0&#44;047&#41;&#46; Os &#243;bitos estavam relacionados &#224; HAI e suas comorbidades&#46; A taxa de sobrevida atuarial foi 92&#44;5&#37; e 97&#44;6&#37; nos pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#59; aos 96 meses de acompanhamento&#44; essas probabilidades foram &#8764;94&#37; e 98&#37;&#46; Aos 150 meses&#44; as probabilidades foram 86&#37; e 98&#37;&#46; No fim do acompanhamento &#40;HAI&#8208;1&#58; 278 meses&#59; HAI&#8208;2&#58; 286 meses&#41;&#44; as probabilidades de sobrevida foram &#8764;70&#37; e 90&#37;&#44; respectivamente&#46; A curva de sobrevida dos pacientes com HAI&#8208;1 foi quase igual &#224; curva de sobrevida geral&#44; pois houve somente dois &#243;bitos entre os 84 pacientes com HAI&#8208;2&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discuss&#227;o</span><p id="par0125" class="elsevierStylePara elsevierViewall">Este constitui o maior estudo cl&#237;nico de crian&#231;as e adolescentes com HAI j&#225; publicado&#46; Nesse grupo do estudo brasileiro&#44; a HAI&#8208;1 foi mais frequente&#46; Al&#233;m disso&#44; os pacientes com HAI&#8208;1 apresentaram risco mais elevado de serem submetidos a Ltx e de &#243;bito&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">O in&#237;cio mais precoce da doen&#231;a para HAI&#8208;2 neste estudo &#233; semelhante ao encontrado na literatura&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">8&#8211;10</span></a> A distribui&#231;&#227;o por sexo feminino&#47;masculino para HAI tamb&#233;m corresponde ao da literatura&#44; ou seja&#44; predomin&#226;ncia do sexo feminino&#44; principalmente entre as pacientes com HAI&#8208;1&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">As manifesta&#231;&#245;es cl&#237;nicas da HAI&#8208;1 e HAI&#8208;2 foram an&#225;logas&#44; exceto o tipo fulminante&#46; A hepatite fulminante &#233; uma manifesta&#231;&#227;o muito rara da doen&#231;a e&#44; quando ocorre&#44; est&#225; mais associada &#224; HAI&#8208;2&#46; Neste estudo&#44; a manifesta&#231;&#227;o fulminante ocorreu com mais frequ&#234;ncia na presen&#231;a da positividade anti&#8208;LKM1&#44; o que &#233; compat&#237;vel com Di Giorgio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> e outros na literura&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">10&#8211;14</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">As manifesta&#231;&#245;es extra&#8208;hep&#225;ticas associadas &#224; HAI s&#227;o vari&#225;veis em frequ&#234;ncia e preval&#234;ncia&#46; As doen&#231;as da tiroide s&#227;o descritas com mais frequ&#234;ncia&#44; semelhantemente &#224;s manifesta&#231;&#245;es extra&#8208;hep&#225;ticas relatadas no estudo de Bittencourt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">15</span></a> e Gregorio et al&#46;&#44; inclusive tireoidite&#44; vitiligo&#44; diabetes tipo 1 e doen&#231;a inflamat&#243;ria intestinal&#44; em 20&#37; das crian&#231;as com HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">13</span></a> Nossos achados s&#227;o diferentes dos de Gregorio et al&#46;&#44; que podem corresponder &#224;s diferen&#231;as regionais e &#224; susceptibilidade gen&#233;tica&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Os escores &#40;1999 e 2008&#41; dos dois tipos de HAI foram compat&#237;veis com os de outros estudos&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">1&#44;2&#44;17</span></a> Os pacientes n&#227;o submetidos a bi&#243;psia no diagn&#243;stico atenderam aos crit&#233;rios internacionais para HAI e n&#227;o mostraram discrep&#226;ncias nos escores em nosso estudo&#46; Mileti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a> examinaram a efic&#225;cia de diagn&#243;stico do escore em crian&#231;as&#46; Inicialmente&#44; a popula&#231;&#227;o pedi&#225;trica n&#227;o foi avaliada de acordo com os crit&#233;rios de 1999&#46; Posteriormente&#44; dois estudos apresentaram resultados controversos com rela&#231;&#227;o ao uso dos dois escores&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">18&#44;19</span></a> Mileti et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">17</span></a> observaram alta sensibilidade e especificidade com o uso dos escores na popula&#231;&#227;o pedi&#225;trica&#59; contudo&#44; tamb&#233;m foram observadas algumas limita&#231;&#245;es&#46; A resposta terap&#234;utica continua um crit&#233;rio de diagn&#243;stico fundamental&#44; principalmente em pacientes sem marcadores de autoimunidade&#44; mesmo se eles n&#227;o atingirem um escore que indique um diagn&#243;stico definitivo de HAI&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Os n&#237;veis de albumina refor&#231;aram a gravidade da doen&#231;a&#44; principalmente em pacientes com HAI&#8208;1&#44; com pioria da fun&#231;&#227;o hep&#225;tica&#46; N&#237;veis elevados de gamaglobulina&#44; principalmente em pacientes com HAI&#8208;1&#44; s&#227;o um sinal significativo no diagn&#243;stico diferenciado entre os tipos de HAI&#46; Esse teste &#233; um importante marcador no diagn&#243;stico da HAI&#8208;1 e o resultado pode ser normal em pacientes com HAI&#8208;2&#44; o que refor&#231;a a diferen&#231;a entre os grupos&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Nenhuma diferen&#231;a ou aumentos significativos foram encontrados em nossos pacientes&#46; Esses dados diferem dos de Di Giorgio et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a> que encontraram n&#237;veis elevados de IgM sem uma explica&#231;&#227;o real&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">11</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Diagnosticar colangite esclerosante continua um desafio&#46; Apesar de a detec&#231;&#227;o de les&#227;o do ducto n&#227;o indicar CEA de forma definitiva&#44; altera&#231;&#245;es histol&#243;gicas ou na CPRM compat&#237;veis com colangite esclerosante n&#227;o s&#227;o sempre observadas em pacientes afetados&#46; N&#237;veis de GGTP persistentemente elevados sugerem envolvimento do trato biliar e o acompanhamento de longo prazo ou avalia&#231;&#227;o de explante possibilita o diagn&#243;stico&#46; N&#227;o foi feita colangiografia em todos os pacientes&#46; Diversos fatores contribu&#237;ram para a dif&#237;cil execu&#231;&#227;o desse exame&#44; por exemplo necessidade de anestesia e os custos&#46; Como o estudo teve um modelo retrospectivo e n&#227;o havia recomenda&#231;&#227;o na literatura&#44; v&#225;rios servi&#231;os foram feitos somente quando o n&#237;vel de GGTP n&#227;o caiu ou quando n&#227;o houve resposta terap&#234;utica aos imunossupressores&#46; Assim&#44; pode haver um vi&#233;s neste estudo com rela&#231;&#227;o &#224; preval&#234;ncia de CEA&#44; o que faz parte dos estudos retrospectivos&#59; contudo&#44; os resultados continuam importantes&#44; devido ao grande n&#250;mero de pacientes inclu&#237;dos&#46; O Comit&#234; de Hepatologia ESPGHAN&#160;recomenda buscar s&#237;ndrome de reposi&#231;&#227;o em pacientes com HAI&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Neste estudo&#44; alguns pacientes n&#227;o foram submetidos a bi&#243;psia hep&#225;tica devido &#224;s contraindica&#231;&#245;es&#44; como coagulopatia &#40;INR alta&#41;&#44; ascite ou trombocitopenia grave&#46; Contudo&#44; todos esses pacientes se enquadram na classifica&#231;&#227;o para HAI de acordo com os crit&#233;rios internacionais&#44; mesmo sem uma histologia de classifica&#231;&#227;o&#46; Al&#233;m disso&#44; os achados da bi&#243;psia do f&#237;gado n&#227;o foram avaliados por um &#250;nico patologista&#44; pois o estudo foi um estudo retrospectivo que coletou dados de v&#225;rios centros&#44; por&#233;m seguiu os crit&#233;rios de consenso dos patologistas brasileiros&#46; O exame do tecido hep&#225;tico antes do tratamento &#233; um importante componente de diagn&#243;stico e as diretrizes recomendam sua feitura na apresenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">7</span></a> Apesar disso&#44; a necessidade de exame do tecido hep&#225;tico antes do tratamento foi contestada em crian&#231;as&#44; pois elas geralmente apresentam disfun&#231;&#227;o hep&#225;tica significativa e coagulopatia&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">22</span></a> Bjo&#776;rnsson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a> mencionaram a import&#226;ncia da histologia no diagn&#243;stico t&#237;pico de HAI e conclu&#237;ram que a maior parte dos pacientes com caracter&#237;sticas de HAO &#233; mais propensa a ter histologias hep&#225;ticas compat&#237;veis&#46; Em adultos&#44; a presen&#231;a de cirrose no quadro cl&#237;nico inicial claramente piora a doen&#231;a&#44; leva a uma taxa de sobrevida de 10 anos de &#8764;60&#37; em compara&#231;&#227;o com 80&#37; dos pacientes sem cirrose&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">23</span></a> Contudo&#44; Radhakrishnan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">24</span></a> observaram que a presen&#231;a de cirrose n&#227;o afeta a sobrevida de longo prazo em crian&#231;as&#46; A cirrose foi o achado predominante na manifesta&#231;&#227;o inicial dos dois tipos de HAI&#59; contudo&#44; essa observa&#231;&#227;o difere dos dados obtidos por Gregorio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a> e Saadah et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">25</span></a> que relataram uma preval&#234;ncia de cirrose de 69&#37; e 38&#37; entre os pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#46; No estudo atual&#44; foram observadas diferen&#231;as nos resultados histopatol&#243;gicos do f&#237;gado entre os grupos de HAI&#44; com uma maior preval&#234;ncia de rosetas e c&#233;lulas plasm&#225;ticas em pacientes com HAI&#8208;1&#44; o que n&#227;o foi relatado na literatura&#46; A presen&#231;a de cirrose na primeira manifesta&#231;&#227;o da doen&#231;a mostra a gravidade da HAI&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">A resposta terap&#234;utica &#233; um dos melhores par&#226;metros para determinar se o perfil cl&#237;nico da hepatite pode ser atribu&#237;do a uma causa imunol&#243;gica&#46; A remiss&#227;o da doen&#231;a &#233; sempre o principal objetivo do tratamento imunossupressor&#46; Em geral&#44; a resposta terap&#234;utica &#233; mais de 70&#37; em pacientes com HAI&#8208;1 e 85&#37; nos com HAI&#8208;2&#44;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">16&#44;26</span></a> semelhante aos achados neste estudo&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Este estudo revelou um tempo reduzido de remiss&#227;o nos pacientes com HAI&#8208;2&#46; Esse achado &#233; incompat&#237;vel com os de Gregorio et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">16</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Uma preocupa&#231;&#227;o importante s&#227;o os comportamentos de n&#227;o ades&#227;o ao tratamento&#44; principalmente entre adolescentes&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">13</span></a> Neste estudo&#44; o tratamento foi interrompido nos dois grupos pelo m&#233;dico e o tratamento tamb&#233;m foi interrompido em alguns pacientes devido &#224; n&#227;o ades&#227;o&#46; Ferreira et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">14</span></a> estudaram crian&#231;as que atingiram remiss&#227;o cl&#237;nica&#8208;laboratorial ap&#243;s imunossupress&#227;o por 24 meses e observaram uma indec&#234;ncia de 54&#44;5&#37; de recidiva da doen&#231;a ap&#243;s o tratamento&#44; mesmo na presen&#231;a de remiss&#227;o histol&#243;gica&#46; Eles n&#227;o identificaram os fatores preditivos associados &#224; recidiva&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">LTx &#233; necess&#225;rio para tratamento de HAI em &#8764;10&#37; dos casos<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">26&#44;27</span></a> e foi feito em 10&#37; dos pacientes pedi&#225;tricos com HAI e 23&#37; dos pacientes com colangite esclerosante&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">26</span></a> Neste estudo&#44; foi feito transplante em 4&#44;7&#37; e 3&#44;5&#37; dos pacientes com HAI&#8208;1 e HAI&#8208;2&#44; respectivamente&#44; indicou&#8208;se que a doen&#231;a foi bem controlada com imunossupressores&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Os fatores de limita&#231;&#227;o deste estudo incluem o fato de ele ser retrospectivo e&#44; consequentemente&#44; haver a possibilidade de vieses e dados incompletos de alguns pacientes&#59; contudo&#44; &#233; importante notar que ele incluiu pacientes de v&#225;rios centros secund&#225;rios e terci&#225;rios de refer&#234;ncia e constitui o maior estudo de crian&#231;as e adolescentes com HAI j&#225; publicado&#46; Os dados apresentados n&#227;o representam a preval&#234;ncia real dos pacientes pedi&#225;tricos com hepatite autoimune no Brasil&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Em resumo&#44; neste grande estudo cl&#237;nico de crian&#231;as e adolescentes brasileiros com HAI&#58; a HAI&#8208;1 foi mais frequente&#59; a HAI&#8208;2 afetou crian&#231;as mais novas&#44; apresentou taxas de remiss&#227;o mais elevadas e se manifestou mais precocemente que a HAI&#8208;1&#59; e os pacientes com HAI&#8208;1 apresentaram maior risco de serem submetidos a LTx e &#243;bito&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflitos de interesse</span><p id="par0200" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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            0 => "Hepatite autoimune"
            1 => "Cl&#237;nico"
            2 => "Laboratorial"
            3 => "Tratamentos"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This large study with a long&#8208;term follow&#8208;up aimed to evaluate the clinical presentation&#44; laboratory findings&#44; histological profile&#44; treatments&#44; and outcomes of children and adolescents with autoimmune hepatitis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed&#46; A questionnaire was used to collect anonymous data on clinical presentation&#44; biochemical and histological findings&#44; and treatments&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Of all patients&#44; 89&#46;6&#37; had autoimmune hepatitis&#8208;1 and 10&#46;4&#37; had autoimmune hepatitis&#8208;2&#46; The female sex was predominant in both groups&#46; The median age at symptom onset was 111&#46;5 &#40;6&#59; 210&#41; and 53&#46;5 &#40;8&#59; 165&#41; months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis&#8208;2&#44; respectively&#46; Acute clinical onset was observed in 56&#46;1&#37; and 58&#46;8&#37; and insidious symptoms in 43&#46;9&#37; and 41&#46;2&#37; of the patients with autoimmune hepatitis&#8208;1 and autoimmune hepatitis&#8208;2&#44; respectively&#46; The risk of hepatic failure was 1&#46;6&#8208;fold higher for autoimmune hepatitis&#8208;2&#46; Fulminant hepatic failure occurred in 3&#46;6&#37; and 10&#46;6&#37; of the patients with autoimmune hepatitis&#8208;1 and autoimmune hepatitis&#8208;2&#44; respectively&#59; the risk was 3&#46;1&#8208;fold higher for autoimmune hepatitis&#8208;2&#46; The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis&#8208;1&#44; while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis&#8208;2&#46; Cirrhosis was observed in 22&#46;4&#37; of the patients&#59; biochemical remission was achieved in 76&#46;2&#37;&#46; The actuarial survival rate was 93&#46;0&#37;&#46; A total of 4&#46;6&#37; underwent liver transplantation&#44; and 6&#46;9&#37; died &#40;autoimmune hepatitis&#8208;1&#58; 7&#46;5&#37;&#59; autoimmune hepatitis&#8208;2&#58; 2&#46;4&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In this large clinical series of Brazilian children and adolescents&#44; autoimmune hepatitis&#8208;1 was more frequent&#44; and patients with autoimmune hepatitis&#8208;2 exhibited higher disease remission rates with earlier response to treatment&#46; Patients with autoimmune hepatitis&#8208;1 had a higher risk of death&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Este estudo com acompanhamento de longo prazo visou a avaliar o quadro cl&#237;nico&#44; os achados laboratoriais&#44; o perfil histol&#243;gico&#44; os tratamentos e os resultados de crian&#231;as e adolescentes com hepatite autoimune&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foram analisados os prontu&#225;rios m&#233;dicos de 828 crian&#231;as e adolescentes com HAI&#46; Foi usado um question&#225;rio para coletar os dados an&#244;nimos sobre o quadro cl&#237;nico&#44; os achados bioqu&#237;micos e histol&#243;gicos e os tratamentos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De todos os pacientes&#44; 89&#44;6&#37; tinham hepatite autoimune&#8208;1 e 10&#44;4&#37; hepatite autoimune&#8208;2&#46; O sexo feminino foi predominante nos dois grupos&#46; A idade m&#233;dia no in&#237;cio dos sintomas foi 111&#44;5 &#40;6&#59; 210&#41; e 53&#44;5 &#40;8&#59; 165&#41; meses nos pacientes com hepatite autoimune&#8208;1 e hepatite autoimune&#8208;2&#44; respectivamente&#46; Foi observado in&#237;cio cl&#237;nico agudo em 56&#44;1&#37; e 58&#44;8&#37; e sintomas insidiosos em 43&#44;9&#37; e 41&#44;2&#37; dos pacientes com hepatite autoimune&#8208;1 e hepatite autoimune&#8208;2&#44; respectivamente&#46; A probabilidade de insufici&#234;ncia hep&#225;tica foi 1&#44;6 vezes maior para hepatite autoimune&#8208;2&#59; 3&#44;6&#37; e 10&#44;6&#37; dos pacientes com hepatite autoimune&#8208;1 e hepatite autoimune&#8208;2&#44; respectivamente&#44; apresentaram insufici&#234;ncia hep&#225;tica fulminante&#59; o risco foi 3&#44;1 vezes maior para hepatite autoimune&#8208;2&#46; Os n&#237;veis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune&#8208;1&#44; ao passo que os n&#237;veis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune&#8208;2&#59; 22&#44;4&#37; dos pacientes apresentaram cirrose e a remiss&#227;o bioqu&#237;mica foi atingida em 76&#44;2&#37;&#46; A taxa de sobrevida atuarial foi de 93&#44;0&#37;&#46; Um total de 4&#44;6&#37; pacientes foram submetidos a transplante de f&#237;gado e 6&#44;9&#37; morreram &#40;hepatite autoimune&#8208;1&#58; 7&#44;5&#37;&#59; hepatite autoimune&#8208;2&#58; 2&#44;4&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nesta grande s&#233;rie cl&#237;nica de crian&#231;as e adolescentes brasileiros&#44; a hepatite autoimune&#8208;1 foi mais frequente e os pacientes com hepatite autoimune&#8208;2 mostraram maiores taxas de remiss&#227;o da doen&#231;a com respostas mais r&#225;pidas aos tratamentos&#46; Os pacientes com hepatite autoimune&#8208;1 apresentaram maior risco de &#243;bito&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Como citar este artigo&#58; Porta G&#44; Carvalho E&#44; Santos JL&#44; Gama J&#44; Borges CV&#44; Seixas RB&#44; et al&#46; Autoimmune hepatitis in 828 Brazilian children and adolescents&#58; clinical and laboratory findings&#44; histological profile&#44; treatments&#44; and outcomes&#46; J Pediatr &#40;Rio J&#41;&#46; 2019&#59;95&#58;419&#8211;27&#46;</p>"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">M&#233;todo de Kaplan&#8208;Meier para analisar a sobrevida de pacientes com hepatite autoimune&#46; A sobrevida &#233; significativamente maior nos pacientes com HAI tipo 2&#46;</p>"
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60; 0&#44;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Masculino&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186 &#40;25&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;15&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;88 &#40;1&#44;02&#44; 3&#44;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;044<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Feminino&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">556 &#40;74&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73 &#40;84&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Quadro cl&#237;nico</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Agudo&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">410 &#40;56&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 &#40;58&#44;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;11 &#40;0&#44;71&#44; 1&#44;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;630<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Insidiosos&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">321 &#40;43&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35 &#40;41&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;005<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fulminante</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27 &#40;3&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;10&#44;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;32 &#40;0&#44;14&#44; 0&#44;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o&#44; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">715 &#40;96&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76 &#40;89&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Insufici&#234;ncia hep&#225;tica</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>INR &#62; 1&#44;5 n &#40;&#37;&#41;&#44; n&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">226 &#40;30&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;40&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;060<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Manifesta&#231;&#245;es extra&#8208;hep&#225;ticas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">183 &#40;24&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;14&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;01 &#40;1&#44;07&#44; 3&#44;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;031<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">555 &#40;75&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73 &#40;85&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Hist&#243;rico familiar de doen&#231;a autoimune</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161 &#40;21&#44;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;21&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;42 &#40;0&#44;60&#44; 1&#44;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;883<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">575 &#40;78&#44;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67 &#40;78&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">34 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">559 &#40;93&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; N &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">485 &#40;83&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">276 &#40;47&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">543 &#40;74&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">76 &#40;89&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;35 &#40;0&#44;17&#59; 0&#44;71&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">184 &#40;25&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;10&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tempo at&#233; a remiss&#227;o &#40;meses&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;m&#237;n&#46;&#59; m&#225;x&#46;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;0&#59; 250&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4 &#40;1&#59; 149&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;meros de recidiva</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mediana &#40;m&#237;n&#46;&#8208;m&#225;x&#46;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;0&#59; 13&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;0&#59; 6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">49 &#40;7&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8 &#40;10&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;68 &#40;0&#44;31&#59; 1&#44;48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">653 &#40;93&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">72 &#40;90&#44;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">35 &#40;4&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3 &#40;3&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;36 &#40;0&#44;41&#59; 4&#44;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;613<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Sim&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">3&#44;36 &#40;0&#44;80&#59; 14&#44;02&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;047<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>N&#227;o &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">680 &#40;92&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Resposta ao tratamento e resultados em pacientes com HAI&#8208;1 e HAI&#8208;2</p>"
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      "seccion" => array:1 [
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          "bibliografiaReferencia" => array:27 [
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                    0 => array:2 [
                      "titulo" => "International Autoimmune Hepatitis Group Report&#58; review of criteria for diagnosis of autoimmune hepatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Alvarez"
                            1 => "P&#46;A&#46; Berg"
                            2 => "F&#46;B&#46; Bianchi"
                            3 => "L&#46; Bianchi"
                            4 => "A&#46;K&#46; Burroughs"
                            5 => "E&#46;L&#46; Cancado"
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                      "doi" => "10.1016/s0168-8278(99)80297-9"
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                        "tituloSerie" => "J Hepatol"
                        "fecha" => "1999"
                        "volumen" => "31"
                        "paginaInicial" => "929"
                        "paginaFinal" => "938"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10580593"
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                      "titulo" => "Simplified criteria for the diagnosis of autoimmune hepatitis"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
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