4.6 Tratamento
4.6.7 Fitoterapia
O resveratrol é um tipo de fenol natural encontrado na casca de uvas, mirtilos, framboesas, amoras e amendoins, e pode ter algumas propriedades preventivas na obesidade e na DFGNA.
(30) Este composto pode proteger contra o stress do RE e a esteatose hepática induzida pela dieta. (202)
Os flavonóides são compostos polifenólicos que fornecem a maioria do sabor e da cor às frutas e vegetais (66) e que têm efeitos hepatoprotetores devido ao seu efeito antioxidante e anti-inflamatório. (66,203)
As vitaminas também podem ser consideradas antioxidantes dietéticos, pois reduzem o stress celular prevenindo a progressão da DFGNA. (66) A vitamina C tem propriedades antioxidantes e anti-inflamatórias demonstrou diminuir os níveis de ROS e aumentar os níveis de enzimas antioxidantes. (204)
A vitamina D tem propriedades anti-inflamatórias e anti fibróticas, e a sua suplementação tem demonstrado melhorar a histologia da DFGNA. (205,206)
5 Conclusões
A DFGNA é a doença hepática mais comum em todo o mundo e é definida como a presença de esteatose em 5% ou mais dos hepatócitos, na ausência de causas secundárias como medicamentos, infeções virais ou consumo excessivo de álcool. Abrange um amplo espetro de condições que variam na gravidade da lesão, desde a ES ou FGNA, EHNA, fibrose e cirrose, podendo eventualmente evoluir para CHC.
A sua prevalência aumentou nos últimos anos, a par com a tendência de aumento da obesidade e doenças metabólicas. Globalmente, a prevalência de DFGNA é estimada em 25% da população adulta do mundo e está a tornar-se rapidamente na principal causa de doença hepática terminal e transplante de fígado. Os doentes com DFGNA apresentam taxas de mortalidade geral aumentadas comparativamente à população em geral, sendo a causa mais comum as DCVs.
É uma doença complexa e progressiva, com uma grande variação inter-doente, sendo que vários fatores contribuem para o desenvolvimento da DFGNA ou da EHNA incluindo fatores genéticos, ambientais e metabólicos. A presença da SM é o fator de risco mais forte para o desenvolvimento de DFGNA e EHNA. Os doentes obesos, com pré-diabetes, DMT2, hipertensão, hipertrigliceridemia ou SM têm maior risco de EHNA e de outras consequências.
É importante esclarecer os fatores genéticos que resultam em diferentes subtipos de DFGNA e que podem levar a uma melhor previsão da progressão da doença e a tratamentos mais eficazes com base em fatores individualizados da doença.
Tanto o FGNA como a EHNA são assintomáticos até a doença avançada sendo difícil o diagnóstico precoce, além disso, o diagnóstico de EHNA requer biópsia hepática, um processo invasivo e com riscos inerentes.
Esta monografia tinha como objetivo principal fazer uma revisão da literatura acerca da abordagem terapêutica no fígado gordo não alcoólico. As primeiras indicações terapêuticas são as alterações de estilo de vida, como modificações na dieta e a prática de exercício para a perda de peso e gestão das comorbilidades. As restantes opções não farmacológicas são a CB, aconselhada em indivíduos obesos com EHNA e o transplante hepático, em fases mais avançadas da doença. Estas indicações permitem reduzir a doença e a sua mortalidade, mas são difíceis de manter, por diversas razões, havendo necessidade da utilização de medidas farmacológicas.
Apesar dos grandes progressos nos últimos anos, existem ainda grandes desafios, pois nenhum fármaco foi aprovado com indicação para esta doença. Diversos fármacos apresentaram resultados promissores e outros encontram-se em fases mais avançadas de ensaios clínicos, com bons resultados, mas ainda assim nenhum demonstrou ser suficientemente benéfico para poder ser considerado a terapêutica específica para a DFGNA. Assim, o tratamento foca-se na gestão das comorbilidades, com o objetivo de reduzir a RI e melhorar a função hepática. Visto a DFGNA ser uma doença multifatorial, um tratamento com diferentes alvos parece ser apropriado, combinando vários fármacos para uma melhor ação. A terapêutica ideal pode evoluir para uma terapia personalizada, quando se entender os mecanismos fisiopatológicos em cada doente, adequando o fármaco a cada doente.
Além disso, há a necessidade de encontrar métodos de diagnóstico não invasivos, para uma melhor e mais precoce identificação do risco e avaliação da progressão da doença. É, também, necessário continuar o estudo acerca da fisiopatologia da DFGNA, que parece ser diferente entre cada doente.
Em 2020, foi proposta a alteração da designação de DFGNA para Doença de Fígado Gordo Associada a Disfunção Metabólica. Este é um termo mais apropriado para descrever as doenças hepáticas associadas ao metabolismo, pois salienta o papel importante da disfunção metabólica no desenvolvimento da doença. Foram, também, definidos novos critérios de diagnóstico que não requerem a exclusão de outras etiologias, como o consumo excessivo de álcool, infeções virais ou medicamentos, necessitando apenas da presença de esteatose hepática e da existência de pelo menos uma de três condições metabólicas (obesidade, DMT2 ou evidência de desregulação metabólica). Estes novos critérios permitem identificar mais doentes em risco e simplificam o diagnóstico.
Em suma, é imprescindível a continuação da investigação nesta área, para garantir resposta aos problemas atuais.
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