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New drugs for the treatment of liver diseases: advances on treatments for hepatocellular carcinoma
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As doenças hepáticas afetam milhões de pessoas todos os anos, tanto em países industrializados como países em desenvolvimento, podendo ter diferentes causas, tais como vírus, distúrbios metabólicos, álcool e alterações imunológicas. A principal consequência de doença hepática em estado avançado é a cirrose, que habitualmente progride para carcinoma hepatocelular.
Apesar da descoberta da vacina do vírus da Hepatite B ter causado um grande impacto na redução da dimensão das doenças hepáticas, bem como na incidência do carcinoma hepatocelular, não foi uma solução, visto que apenas se trata de uma das possíveis causas de doença hepática, e ainda existe população não vacinada.
Para além disso, o aumento de distúrbios metabólicos, tais como obesidade e diabetes, nos países desenvolvidos, que são maioritariamente causados pela dieta hipercalórica ocidental, leva ao aumento do número de pacientes com cirrose e, em última instância, com carcinoma hepatocelular.
O diagnóstico do carcinoma hepatocelular, atualmente realizado através de técnicas de imagem e por determinação dos níveis séricos de enzimas hepáticas, deve ser efetuado o mais cedo possível, de modo a permitir um bom prognóstico e a possibilidade de transplante, que é atualmente o único tratamento curativo. Programas de rastreio estão em falta na maioria dos países e é algo que precisa de ser resolvido, visto ser uma opção de baixos custos e recursos para diminuir a globalidade de casos de carcinoma hepatocelular.
Para estados iniciais de carcinoma hepatocelular, as opções terapêuticas são maioritariamente cirúrgicas, incluindo ressecção e transplante hepático, apesar de existir também alguma farmacologia. O primeiro fármaco sistémico aprovado foi o sorafenib, em 2008, e apesar dos esforços e constante investigação, apenas 10 anos depois foram descobertos novos fármacos eficazes.
Para melhor perceber o desenvolvimento, diagnóstico e tratamento do carcinoma hepatocelular, começar-se-á por introduzir o fígado: células hepáticas, principais funções e a importância no organismo humano; de seguida serão descritas as doenças hepáticas mais comuns. Por último, o foco centrar-se-á no carcinoma hepatocelular, referindo a incidência, fisiopatologia, atuais opções terapêuticas, mas também opções promissoras em desenvolvimento.
Liver diseases affect millions of people every year, both in industrialized and developing countries, having several different etiologies, such as virus, metabolic disorders, alcohol and immunological disorder. Cirrhosis is the primary consequence of advanced liver disease, which commonly progresses to hepatocellular carcinoma. Although the Hepatitis B Virus vaccine discovery had a great impact in reducing liver disease burden, and also hepatocellular carcinoma incidence, it was not a full solution, as the Hepatitis B Virus is only one of the possible causes of liver diseases, and there are still many unvaccinated people. The worldwide increase of metabolic disorders, such as obesity and diabetes, mainly due to the hypercaloric western diet, is leading to the rise of cirrhosis and, consequently, hepatocellular carcinoma. The diagnosis of hepatocellular carcinoma, which is currently approached through imaging techniques and measurement of serum levels of specific hepatic enzymes, should be perform as early as possible, to allow for a better prognosis and the possibility of liver transplant, which currently is the only curative treatment option. Screening programs are lacking in most countries and this needs to be addressed, since it constitutes a low-cost and low-resource tool to decrease hepatocellular carcinoma global burden. Treatment options for hepatocellular carcinoma in early stages are mostly surgical, including liver resection and transplant, but different drugs are also available. The first approved systemic drug for hepatocellular carcinoma was sorafenib, in 2008, and despite the efforts and constant research, only 10 years later novel drugs were discovered. To better understand development, diagnosis and treatment of hepatocellular carcinoma, we will start with an overview of the liver: different types of hepatic cells and its role in the human organism; we will then describe the most common liver diseases. Last but not least, we will focus on hepatocellular carcinoma, referring to incidence, physiopathology, current treatment options, but also on-going research and novel therapeutics approaches.
Liver diseases affect millions of people every year, both in industrialized and developing countries, having several different etiologies, such as virus, metabolic disorders, alcohol and immunological disorder. Cirrhosis is the primary consequence of advanced liver disease, which commonly progresses to hepatocellular carcinoma. Although the Hepatitis B Virus vaccine discovery had a great impact in reducing liver disease burden, and also hepatocellular carcinoma incidence, it was not a full solution, as the Hepatitis B Virus is only one of the possible causes of liver diseases, and there are still many unvaccinated people. The worldwide increase of metabolic disorders, such as obesity and diabetes, mainly due to the hypercaloric western diet, is leading to the rise of cirrhosis and, consequently, hepatocellular carcinoma. The diagnosis of hepatocellular carcinoma, which is currently approached through imaging techniques and measurement of serum levels of specific hepatic enzymes, should be perform as early as possible, to allow for a better prognosis and the possibility of liver transplant, which currently is the only curative treatment option. Screening programs are lacking in most countries and this needs to be addressed, since it constitutes a low-cost and low-resource tool to decrease hepatocellular carcinoma global burden. Treatment options for hepatocellular carcinoma in early stages are mostly surgical, including liver resection and transplant, but different drugs are also available. The first approved systemic drug for hepatocellular carcinoma was sorafenib, in 2008, and despite the efforts and constant research, only 10 years later novel drugs were discovered. To better understand development, diagnosis and treatment of hepatocellular carcinoma, we will start with an overview of the liver: different types of hepatic cells and its role in the human organism; we will then describe the most common liver diseases. Last but not least, we will focus on hepatocellular carcinoma, referring to incidence, physiopathology, current treatment options, but also on-going research and novel therapeutics approaches.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Doenças hepáticas Carcinoma hepatocelular Terapêutica Investigação Mestrado integrado - 2020