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Será o carcinoma hepatocelular um reservatório vírico em pacientes com hepatite C tratados com antiovíricos de ação direta?
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Authors
Abstract(s)
Os antivíricos de ação direta (AADs) revolucionaram o tratamento da infeção pelo vírus da hepatite C (VHC), substituindo terapias mais antigas baseadas em interferão que apresentavam problemas de tolerabilidade e eficácia. Recentemente, o carcinoma hepatocelular (CHC) foi identificado como um preditor significativo de menor eficácia do tratamento com AADs. No entanto, continua por esclarecer por que pacientes com CHC ativo têm uma pior resposta aos AADs. Várias hipóteses foram levantadas, incluindo o eventual comportamento do CHC como reservatório para o VHC durante o tratamento com AADs. Neste estudo, testamos esta hipótese, caracterizando quantitativamente o VHC em tecido do CHC e em tecido hepático não tumoral obtido a partir de pacientes hepatetomizados em diferentes fases de tratamento com AADs. Efetuou-se a quantificação por imunofluorescência direcionada à proteína não estrutural 3 (NS3) do VHC. Os resultados mostraram que durante o tratamento com AAD ocorre uma redução da densidade de VHC, tanto no tecido tumoral como não tumoral, mas que na fase inicial o VHC parece concentrar-se mais no CHC. Estes dados sugerem que o tecido tumoral do CHC pode ser um reservatório para o VHC.
ABSTRACT - The direct-acting antivirals (DAAs) revolutionized the treatment of hepatitis C virus (HCV) infection, replacing older interferon-based therapies that had issues with tolerability and efficacy. Recently, hepatocellular carcinoma (HCC) has been identified as a significant predictor of non-response or decreasing efficacy of DAAs treatment. However, it is still unclear why patients with active HCC have a lower response to DAAs, and several hypotheses have been raised, including the role of HCC as a reservoir for HCV during DAA treatment. Herein, we tested this hypothesis by quantitatively characterizing HCV in HCC tissue and non-tumoral tissue collected from hepatectomized patients at different stages of DAA treatment. Quantification was performed by immunofluorescence, targeting the HCV non-structural protein 3 (NS3). The results showed that during DAA treatment, despite a reduction in HCV density in both tumoral and non-tumoral tissue, in the initial phase, HCV appears to concentrate more in HCC. The results suggest that HCC tumoral tissue may be acting as a reservoir for HCV.
ABSTRACT - The direct-acting antivirals (DAAs) revolutionized the treatment of hepatitis C virus (HCV) infection, replacing older interferon-based therapies that had issues with tolerability and efficacy. Recently, hepatocellular carcinoma (HCC) has been identified as a significant predictor of non-response or decreasing efficacy of DAAs treatment. However, it is still unclear why patients with active HCC have a lower response to DAAs, and several hypotheses have been raised, including the role of HCC as a reservoir for HCV during DAA treatment. Herein, we tested this hypothesis by quantitatively characterizing HCV in HCC tissue and non-tumoral tissue collected from hepatectomized patients at different stages of DAA treatment. Quantification was performed by immunofluorescence, targeting the HCV non-structural protein 3 (NS3). The results showed that during DAA treatment, despite a reduction in HCV density in both tumoral and non-tumoral tissue, in the initial phase, HCV appears to concentrate more in HCC. The results suggest that HCC tumoral tissue may be acting as a reservoir for HCV.
Description
Mestrado em Tecnologias Clínico-Laboratoriais
Keywords
Vírus da hepatite C Carcinoma hepatocelular Reservatório vírico Antivíricos de ação direta Hepatitis C virus Hepatocellular carcinoma Virus reservoir Direct acting antivirals MTCL
Citation
Negrinho AP. Será o carcinoma hepatocelular um reservatório vírico em pacientes com hepatite C tratados com antiovíricos de ação direta? [dissertation]. Lisboa: Escola Superior de Tecnologia da Saúde de Lisboa/Instituto Politécnico de Lisboa; 2024.
Publisher
Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa