O hepatocarcinoma na infecção do HBV é controlado pelo uso de entecavir, interferon e tenofovir: supressão viral e restauração da descompensação hepática
##plugins.themes.bootstrap3.article.main##
Resumo
Objetivo: Elucidar como as terapias com interferons e análogos de nucleotídeos em pacientes infectados pelo vírus da hepatite B ocasionam a reversão de cirrose hepática e hepatocarcinoma. Revisão bibliográfica: O entecavir demonstrou benefícios virológicos e bioquímicos, reduzindo a incidência de mutações resistentes aos medicamentos, sendo associado a um risco menor de óbito. Os interferons (IFNs) têm sido usados para tratar hepatite B/C crônica, IFNs induzem a expressão de APOBEC3G, com ativação do STAT3 inibindo o HBV, complexos desses IFNs ativam o transdutor de sinal da quinase ativada por Janus (JAK) e o ativador da via de transcrição (STAT), levando a expressão de genes estimulados por IFN (ISGs). Estudos com tenofovir para hepatite B sugerem que ele reverte a fibrose hepática, o tenofovir é hidrolisado pelas esterases intestinais e plasmáticas, sendo metabolizado principalmente intracelularmente pela catepsina A. Considerações finais: Os IFNs ativam células do sistema imunológico responsáveis pela resposta antiviral, o entecavir atua como terminador de cadeia de DNA do HBV e o tenofovir está associado a reversão da fibrose hepática e restauração da função renal.
##plugins.themes.bootstrap3.article.details##
Copyright © | Todos os direitos reservados.
A revista detém os direitos autorais exclusivos de publicação deste artigo nos termos da lei 9610/98.
Reprodução parcial
É livre o uso de partes do texto, figuras e questionário do artigo, sendo obrigatória a citação dos autores e revista.
Reprodução total
É expressamente proibida, devendo ser autorizada pela revista.
Referências
2. CHEN Y, TIAN Z. HBV-Induced Immune Imbalance in the Development of HCC. Frontiers in Immunology, 2019; 10:2048.
3. CHISARI F, et al. Pathogenesis of hepatitis B virus infection. Pathologie Biologie, 2010; 58(4):258-266.
4. CLERCQ ED, et al. Antiviral Treatment of Chronic Hepatitis B Virus (HBV) Infections. Viruses, 2010; 6(2):1279-1305.
5. FEIG JL, et al. The antiviral drug tenofovir, an inhibitor of Pannexin-1-mediated ATP release, prevents liver and skin fibrosis by downregulating levels in the liver and skin. Plos One, 2017; 12(11):e0188135.
6. HAMLIN AN, et al. Genetic variations of kinases and activation of nucleotide analog reverse transcriptase inhibitor tenofovir. Pharmacogenomics, 2019; 20(2):105-111.
7. JIANG Y, et al. The Mechanisms of HBV-Induced Hepatocellular Carcinoma. Journal of Hepatocellular Carcinoma, 2021; 8:435-450.
8. KIM JH, et al. Lamivudine versus Entecavir for Newly Diagnosed Hepatocellular Carcinoma. Gut and Liver, 2016; 10(9):939-947.
9. LI Q, et al. Interferon and interferon-stimulated genes in HBV treatment. Frontiers in Immunology, 2022; 13:1034968.
10. LI X, et al. Pharmacokinetics of tenofovir Alafenamide Fumarate and Tenofovir in the Chinese People: Effects of Non-Genetic Factors and Genetic Variations. Pharmacogenomics and Personalized Medicine, 2021; 14:1315-1329.
11. LIN F-C, YOUNG HA. Interferons: Success in anti-viral immunotherapy. Cytokines & Growth Factor Reviews, 2014; 25(4):369-376.
12. LOVETT GC, et al. Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience. World Journal of Hepatology, 2017; 9(1):48-56.
13. MACBRAYNE CE, et al. Effects of sofosbuvir-based hepatitis C treatment on the pharmacokinetics of tenofovir in HIV/HCV - coinfected individuals receiving tenofovir disoproxil fumarate. Journal of Antimicrobial Chemotherapy, 2018; 73(8):2112-2119.
14. MERTOWSKA P, et al. Immunomodulatory Role of Interferon in Viral and Bacterial Infections. International Journal of Molecular, 2023; 24(12):10115.
15. MOHD-ISMAIL NK, et al. Mapping The Interactions of HBV cccDNA with Host Factors. International Journal of Molecular Sciences, 2019; 20(17):4276.
16. NEVOLA R, et al. HBV Infection and Host Interactions: The Role in Viral Persistent and Oncogenesis. International Journal of Molecular Sciences, 2023; 24(8):7651.
17. NOVOTNY LA, et al. Review of Lambda Interferon in Hepatitis B Virus Infection: Outcomes and Therapeutics Strategies. Viruses, 2021; 13(6):1090.
18. SCHOLLMEIR A, et al. Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis. International Journal of Molecular Sciences, 2023; 24(5):4964.
19. SHORAKA S, et al. The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways. Frontiers in Microbiology, 2023; 14:1213145.
20. STADLER D, et al. Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20. EMBO reports, 2021; 22(6): e49568.
21. TAKAMATSU Y, et al. 4’ -Modified Nucleoside Analogs: Potent Inhibitors Active against Entecavir-resistant Hepatitis B Virus. Hepatology, 2015; 62(4):1024-1036.
22. TAN G, et al. When Hepatitis B Virus Meets Interferons. Frontiers in Microbiology, 2018; 9:1611.
23. WANG S-H, et al. Unique Features of Hepatitis B Virus-Related Hepatocellular Carcinoma in Pathogenesis and Clinical Significance. Cancers, 2021; 13(10):2454.
24. WASSNER C, et al. A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide. Journal of the International Association of Provides of AIDS Care, 2020; 19:1-10.
25. WOO ASJ, et al. Alpha-interferon treatment in hepatitis B. Annals of Translational Medicine, 2017; 5(7):159.
26. XU F, et al. Type III interferon-induced CBFβ inhibits HBV replication by hijacking HBx. Cellular & Molecular Immunology, 2019; 16(4):357-366.
27. YANG M, XU X. Important roles of transporters in the pharmacokinetics of anti-viral nucleoside/nucleotide analogs. Expert Opinion on Drug Metabolism & Toxicology, 2022; 18(7-8):483-505.
28. YASUTAKE Y, et al. HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir. Scientifics Reports, 2018; 8:1624.
29. YIN G-Q, et al. New Therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection: Increase of entecavir dosage. World Journal of Gastroenterology, 2021; 27(8):666-676.