Affiliation:
1. Institute of Immunology Dr. Nicolás E. Bianco C., Faculty of Medicine, Universidad Central de Venezuela, Caracas 1040, Venezuela
2. Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, 779 00 Olomouc, Czech Republic
3. The Czech Advanced Technology and Research Institute (Catrin), Palacky University, 779 00 Olomouc, Czech Republic
Abstract
Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN–RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients’ treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV–HCV and HCV–HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV–HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.
Funder
National Fund for Science, Technology, and Innovation of Venezuela
National Institute of Virology and Bacteriology
Subject
Microbiology (medical),Molecular Biology,General Medicine,Microbiology
Reference182 articles.
1. The 2020 Nobel Prize for Medicine or Physiology for the Discovery of Hepatitis C Virus: A Triumph of Curiosity and Persistence;Ghany;Hepatology,2021
2. Acute hepatitis C virus infection: Clinical update and remaining challenges;Liu;Clin. Mol. Hepatol.,2023
3. Virology and cell biology of the hepatitis C virus life cycle—An update;Dubuisson;J. Hepatol.,2014
4. Epidemiology and natural history of hepatitis C virus infection;Lee;World J. Gastroenterol.,2014
5. Alazard-Dany, N., Denolly, S., Boson, B., and Cosset, F.L. (2019). Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets. Viruses, 11.