Com a existência de fármacos cada vez menos hepatotóxicos para o tratamento dirigido do VIH e com os fatores de risco nesta população cada vez mais idênticos aos da população geral para o desenvolvimento e progressão de FGNA, é de esperar que os alvos terapêuticos sejam os mesmos. Contudo, apesar do grande número de ensaios
sobre esta temática que estão a decorrer, estes não abrangem PVIH devido ao risco associado de interações medicamentosas que pode haver com o uso concomitante da TARc (Guaraldi et al., 2020).
Os fármacos em pipeline mais prováveis de serem aprovados para o tratamento dirigido da EHNA são o Aramchol, o Ácido Obeticólico, Dapaglifozina, Oltiparaz e o Resmetirom e que se encontram descritos na Tabela 2 (Guaraldi et al., 2020; Jeong, 2020).O Elafibranor (agonista duplo PPAR-α/δ que regula o metabolismo lipídico e da insulina) e o Cenicriviroc (antagonista dos recetores CCR2 e CCR5 ,envolvidos na patogénese da inflamação hepática e da fibrose com o objetivo de diminuir a inflamação, aterosclerose e dislipidemia) eram considerados potenciais fármacos para o tratamento da EHNA, contudo os seus ensaio clínicos de fase 3, RESOLVE-IT (ClinicalTrials.gov, NCT0204403) e AURORA (ClinicalTrials.gov, NCT03028740), respetivamente, foram cancelados devido à sua falta de eficácia.
Tabela 2. Fármacos em ensaio clínico fase 3 para EHNA
Adaptado de Lake et. al, 2020 Expert Panel Review on Non-Alcoholic Fatty Liver Disease in Persons With HIV
Conclusão
O FGNA é uma importante causa de comorbilidade em PVIH. A sua elevada prevalência, face à população em geral, deve-se a mecanismos da própria infeção por VIH e à terapêutica dirigida que é instituída. Contudo, os principais mecanismos de etiopatogénese têm vindo a mudar, passando a ser o principal mecanismo aquele que também ocorre na população em geral, contribuindo para isso alterações de estilos de vida com o aumento do excesso de peso e obesidade e também de outros componentes do Síndrome Metabólico .
Apesar do rastreio bioquímico não estar recomendado rotineiramente devido à sua baixa sensibilidade, torna-se imperativo que profissionais de saúde estejam alerta para esta problemática a fim de evitar a evolução natural da doença para cirrose hepática ou CHC. Atualmente, há vários métodos não invasivos para estadiamento e monitorização da doença através da combinação de parâmetros bioquímicos e antropométricos e também através de métodos imagiológicos que estão amplamente distribuídos nos cuidados de saúde e podem ser uma boa alterativa à Biópsia Hepática.
Atualmente não existe um tratamento dirigido para a abordagem do FGNA em PVIH, recomendando-se uma abordagem idêntica à da população em geral, onde o principal objetivo assenta em mudanças do estilo de vida e na perda ponderal. Nesta população, o único fármaco aprovado para a redução de gordura abdominal foi a Tesamorelina. Apesar dos ensaios clínicos que estão a decorrer com objetivo de tratamento dirigido, estes não abrangem PVIH devido às possíveis interações medicamentosas que possam advir do uso concomitante com TARc. Assim, para uma melhor a esta população, torna-se necessários estudos que abranjam esta população.
Deste modo, e até haver uma terapêutica dirigida eficaz e que não interfira com o uso da TARc, a terapêutica primordial assenta em alterações dos estilos de vida passando pela adoção da Dieta Mediterrânica, perda ponderal e exercício físico.
Agradecimentos
Com a realização desta revisão narrativa, concluo de forma quase oficial o meu percurso como estudante do Mestrado Integrado em Medicina, pela Faculdade de Medicina da Universidade de Lisboa. Foram 6 longos e intensos anos dos quais eu tenho muito orgulho porque me fez crescer enquanto profissional e, principalmente, como pessoa.
Primeiramente, quero agradecer à Professora Doutora Helena Cortez-Pinto e à Mestre Sara Policarpo pelas disponibilidades e conselhos bem como pela simpatia e paciência na orientação desta revisão.
Um agradecimento especial aos meus pais, Guida e Joaquim, que mesmo longe, estiveram sempre perto. Acreditaram em mim e apoiaram-me incondicionalmente, tornando todos os impossíveis, possíveis. A eles devo toda a força e determinação que me fizeram lutar para alcançar sempre os meus sonhos.
Quero agradecer aos meus amigos mais próximos, aqueles que fazem parte da família que eu escolhi e que me fazem sentir sempre em casa mesmo a 220 quilómetros de distância.
Por fim, quero agradecer a todos aqueles que se cruzaram ao longo do meu percurso e que deixarão uma marca importante na minha vida.
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