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Novas abordagens terapêuticas no tratamento da doença de fígado gordo não alcoólico
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Abstract(s)
A doença de fígado gordo não alcoólico define-se como a acumulação excessiva de lípidos no fígado. Engloba a esteatose hepática isolada até à esteato-hepatite não alcoólica, onde já existe inflamação, fibrose e morte celular. Cerca de 30-40% dos casos de esteatose simples evoluem para esteato-hepatite não alcoólica, a qual está associada a um pior prognóstico e que se estima futuramente vir a tornar-se a principal causa de transplante hepático. Atinge cerca de 20-30% da população mundial, tendo vindo a aumentar de forma exponencial a sua prevalência, acompanhando a tendência de aumento da síndrome metabólica, frequentemente presente nos indivíduos com esta doença.
O objetivo final desta monografia é o de sistematizar a informação existente acerca do tratamento da doença de fígado gordo não alcoólico. A primeira opção de tratamento passa pela alteração do estilo de vida acompanhada de perda de peso, através de dieta e da prática de atividade física. Contudo, esta estratégia acaba por não ter sucesso na grande maioria dos casos, daí que seja essencial conjugá-la com uma abordagem farmacológica que trate os vários componentes da síndrome metabólica que possam estar presentes ou que contrarie os mecanismos fisiopatológicos da doença (stress oxidativo, inflamação, fibrose, apoptose).
Até ao momento ainda nenhum fármaco demonstrou possuir um benefício terapêutico suficientemente significativo para ser aprovado como terapêutica específica da doença de fígado gordo não alcoólico. Considerando a previsão de que a prevalência desta patologia irá continuar a aumentar, o vazio terapêutico associado a esta doença torna-se um assunto problemático, sendo imprescindível que a investigação na área continue. É assim imperativo que se aprofunde a sua fisiopatologia e se identifique quais os fatores de risco associados a pior prognóstico, de maneira a ser possível dirigir eficazmente a terapêutica, descobrir novos alvos e adequar o tratamento a cada indivíduo.
Non alcoholic fatty liver disease is defined as excessive lipid accumulation in the liver. It goes from simple hepatic steatosis to non alcoholic steatohepatitis where inflammation, fibrosis and cell death are already present. Around 30-40% of simple steatosis cases progress to non alcoholic steatohepatitis, which has a worse prognosis and it is estimated to become the leading cause of hepatic transplantation in the near future. It reaches approximately 20-30% of the world population and its prevalence is increasing exponentially, following the tendency of increase of the metabolic syndrome, which is very common among individuals with this disease. The final goal of this monography is to systemize the existing information about the treatment of the non alcoholic fatty liver disease. The first option of treatment consists of lifestyle changes with loss of weight through diet and physical activity. Unfortunately, this strategy is unsuccessful in most cases, thus it is essential to be conjugated with a pharmacological approach that treats the several components of the metabolic syndrome or halts the physiopathological mechanisms of the disease (oxidative stress, inflammation, fibrosis, apoptosis). Until now, no drug has demonstrated having therapeutic benefit high enough to be approved as specify treatment for non alcoholic fatty liver disease. With the notion that the prevalence of this pathology is going to keep rising, the therapeutic emptiness associated with this disease becomes a problematic issue, making it necessary that the investigation in this field continues. Therefore it is essential to know more about the disease pathology and to identify risk factors associated with worse prognosis in order to make it possible to effectively focus the treatment, discover new targets and adapt the treatment to each individual.
Non alcoholic fatty liver disease is defined as excessive lipid accumulation in the liver. It goes from simple hepatic steatosis to non alcoholic steatohepatitis where inflammation, fibrosis and cell death are already present. Around 30-40% of simple steatosis cases progress to non alcoholic steatohepatitis, which has a worse prognosis and it is estimated to become the leading cause of hepatic transplantation in the near future. It reaches approximately 20-30% of the world population and its prevalence is increasing exponentially, following the tendency of increase of the metabolic syndrome, which is very common among individuals with this disease. The final goal of this monography is to systemize the existing information about the treatment of the non alcoholic fatty liver disease. The first option of treatment consists of lifestyle changes with loss of weight through diet and physical activity. Unfortunately, this strategy is unsuccessful in most cases, thus it is essential to be conjugated with a pharmacological approach that treats the several components of the metabolic syndrome or halts the physiopathological mechanisms of the disease (oxidative stress, inflammation, fibrosis, apoptosis). Until now, no drug has demonstrated having therapeutic benefit high enough to be approved as specify treatment for non alcoholic fatty liver disease. With the notion that the prevalence of this pathology is going to keep rising, the therapeutic emptiness associated with this disease becomes a problematic issue, making it necessary that the investigation in this field continues. Therefore it is essential to know more about the disease pathology and to identify risk factors associated with worse prognosis in order to make it possible to effectively focus the treatment, discover new targets and adapt the treatment to each individual.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Keywords
Doença de fígado gordo não alcoólico Esteato-hepatite não alcoólica Tratamento da doença de fígado gordo não alcoólico Mestrado Integrado - 2017