Efeitos nocivos do uso prolongado de álcool documentados em instantâneo de proteínas sanguíneas
O bioquímico Jon Jacobs analisou o sangue de pacientes com doenças e condições como Ebola, câncer, tuberculose, hepatite, diabetes, doença de Lyme, lesão cerebral e gripe. Mas ele nunca viu a química do sangue dar tão errado como quando ele...
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)
Domínio público
O bioquímico Jon Jacobs analisou o sangue de pacientes com doenças e condições como Ebola, câncer, tuberculose, hepatite, diabetes, doença de Lyme, lesão cerebral e gripe.
Mas ele nunca viu a química do sangue dar tão errado como quando ele e seus colegas analisaram em profundidade a atividade da proteína no sangue de pacientes com hepatite associada ao álcool , uma forma grave de doença hepática causada pelo consumo excessivo de álcool por muitos anos.
"As proteínas nesses pacientes são mais desreguladas do que em qualquer outro plasma sanguíneo que analisamos", disse Jacobs, bioquímico do Laboratório Nacional do Pacífico Noroeste do Departamento de Energia. "Quase dois terços das proteínas que medimos estão em níveis incomuns. Este é um instantâneo do que está acontecendo no corpo de uma pessoa com esta doença e reflete o quão grave é a doença."
Esse "instantâneo" é uma medida de proteínas que mudam em pacientes com a doença. A combinação única de alterações na atividade da proteína marca um passo importante para o desenvolvimento de um exame de sangue simples para diagnosticar a hepatite associada ao álcool.
Jacobs e colegas, incluindo cientistas e médicos do Veteran Affairs Long Beach Healthcare System e da Universidade de Pittsburgh, publicaram suas descobertas no American Journal of Pathology . Os autores correspondentes do estudo são Jacobs e Timothy Morgan, um gastroenterologista da VA Long Beach que tratou pacientes com a doença por mais de 35 anos.
Hepatite associada ao álcool: há muito tempo em construção
As descobertas não surpreendem Morgan.
"Esses indivíduos estão muito doentes. Esses pacientes bebem muito álcool, normalmente mais de um pacote de seis cervejas ou mais de uma garrafa de vinho ou mais de quatro doses de bebida alcoólica por dia há mais de 10 anos", disse Morgan, que também é professor de medicina na UCI Health.
A doença é mais grave do que outras doenças hepáticas que podem ser causadas pelo álcool, incluindo cirrose hepática e fígado gorduroso. Cerca de 10 por cento dos pacientes com hepatite associada ao álcool morrem dentro de um mês após o diagnóstico; cerca de 25% morrem em seis meses. Muitas vezes, eles estão nos últimos espasmos de uma doença que está se desenvolvendo há muitos anos.
Morgan estima que já tratou mais de 400 pacientes com a doença. Para melhorar o atendimento que presta aos pacientes e aprender mais sobre a doença, Morgan reuniu pesquisadores, médicos e pacientes do Southern California Alcoholic Hepatite Consortium, PNNL, o InTeam Consortium com sede na Universidade de Pittsburgh e outros.
O estudo incluiu a análise de amostras de sangue ou tecido de 106 pessoas. Estes incluíram 57 pacientes com hepatite associada ao álcool e 49 outros que tinham doença hepática gordurosa não alcoólica , outras doenças hepáticas relacionadas ao álcool, como cirrose, ou que eram saudáveis.
A equipe do PNNL usou espectrometria de massa sensível para medir mais de 1.500 proteínas no sangue dos participantes do estudo. Embora a hepatite associada ao álcool tenha um impacto esmagador nas proteínas do sangue, a equipe do PNNL identificou um grupo de 100 proteínas que são alteradas nos pacientes e parecem conduzir a doença específica. Muitas proteínas eram menos abundantes nesses pacientes; alguns eram mais abundantes. As proteínas afetadas cobrem a gama de funções corporais, incluindo inflamação, imunidade e coagulação, bem como a função hepática fundamental.
Os resultados correlacionaram-se bem com estudos anteriores de hepatite associada ao álcool envolvendo tecidos hepáticos de pacientes. Ramon Bataller, chefe de hepatologia da Universidade de Pittsburgh e autor do estudo atual, já havia caracterizado a atividade genética no fígado de pacientes com a doença. Sua equipe descobriu que as proteínas centrais alteradas no sangue dos pacientes com a doença se correlacionam diretamente com a vasta desregulação dos genes e proteínas no fígado, ligando a expressão sanguínea de proteínas específicas da doença à função hepática.
Ambos os estudos apontam para um papel central para uma molécula conhecida como HNF4A, que é um centro central da atividade do gene do fígado. O HNF4A também está envolvido em doenças como câncer pancreático e diabetes.
Um objetivo: um biomarcador para diagnóstico, monitoramento
O trabalho é um passo importante para o desenvolvimento de um biomarcador de sangue – um exame de sangue – que mostraria que alguém tem hepatite associada ao álcool.
"O diagnóstico de hepatite associada ao álcool pode ser difícil, caro e às vezes pode levar vários dias", disse Morgan. "Fazer um exame de sangue para o diagnóstico de HA ajudaria os médicos a fazer o diagnóstico de forma rápida, segura, precisa e menos dispendiosa do que com uma biópsia hepática".
A equipe está conduzindo mais estudos para ver se as mesmas alterações nas proteínas podem ser usadas para monitorar como os pacientes estão respondendo ao tratamento. Os médicos geralmente usam esteroides para reduzir a inflamação, mas o tratamento deixa os pacientes vulneráveis a infecções.
“Esses dados nos ajudam a entender o que está acontecendo com esses pacientes e esperamos que nos forneça uma ferramenta adicional para monitorar como os pacientes estão respondendo aos tratamentos”, disse Jacobs.
Além de Jacobs, os autores do PNNL incluem Marina Gritsenko, Richard D. Smith e Le Z. Day, bem como o ex-cientista do PNNL Komal Kedia, agora na Merck. O primeiro autor do estudo é Josepmaría Argemí, da Universidade de Pittsburgh e da Universidade de Navarra.
Mais informações: Josepmaria Argemi et al, Análise proteômica e transcritômica integrada identifica biomarcadores plasmáticos de falha hepatocelular na hepatite associada ao álcool, The American Journal of Pathology (2022). DOI: 10.1016/j.ajpath.2022.08.009
Informações do periódico: American Journal of Pathology