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ABSTRACT
Introduction
With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease.
Areas covered
The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches.
Expert Opinion
DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO’s goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.
Plain Language Summary
Hepatitis C virus (HCV) is an insidious pathogen. Most people infected with HCV will develop chronic infections that may not give any symptoms for years or decades but eventually lead to liver disease and liver cancer. It is essential to diagnose infected individuals as soon as possible and start the treatment to increase the elimination of the virus from the organism and prevent harmful long-term effects.
Fortunately, these goals are possible nowadays, and this is due to a remarkable example of translational research at work. The discovery of the virus in 1989 (for which Harvey J. Alter, Michael Houghton, and Charles M. Rice received the Nobel Prize in 2020) was followed by the rapid development of diagnostic tests and later by the introduction of the first interferon therapies, which had numerous shortcomings. The revolution started in 2011 when the first oral drugs that act directly on HCV (direct-acting antivirals, DAAs) were registered. Another giant leap for HCV treatment was made in 2018 when the combinations of DAAs that act on different HCV genotypes were introduced.
In this paper, we review in detail the DAAs used to treat HCV infection and explain different combinations in which they can be used while showing their favorable safety profile, short-term and convenient treatment regimen, and impressive effectiveness in clearing HCV infection. Although we believe eliminating HCV is eventually reachable, we also argue that there is room for improvement. HCV testing and DAAs availability must improve in selected groups, including people without health insurance, prisoners, and drug addicts. There are still people living with chronic HCV infection without knowing it. Their identification and start of effective treatment is equal to savings in future medical care related to liver disease and cancer, not to mention benefits from the individual health perspective. In addition, and in line with a popular phrase that prevention is better than cure, it is reasonable to pursue the development of the HCV vaccine, which is currently unavailable. The last word on managing the health burden caused by this pathogen is yet to be said.
Article highlights
Current treatment of hepatitis C with orally administered direct-acting antivirals is considered highly effective and provides a good safety profile compared to previous IFN-based regimens.
To further improve the treatment, the focus should remain on the underserved groups, such as those without health insurance, incarcerated, and struggling with substance abuse.
The goal for the future involves such areas as the possibility of initiating treatment during pregnancy and the development of an effective vaccine.
Abbreviation
| ART | = | Antiretroviral therapy |
| ASV | = | Asunaprevir |
| BOC | = | Boceprevir |
| BCRP | = | Breast cancer resistance protein |
| CAS | = | Chemical Abstracts Service Registry Number |
| CP | = | Child-Pugh Classification |
| CHC | = | Chronic hepatitis C |
| CKD | = | Chronic kidney disease |
| CYP | = | cytochrome P450 |
| CYP2B6 | = | cytochrome P4502B6 |
| CYP2C8 | = | cytochrome P4502C8 |
| CYP3A4 | = | cytochrome P4503A4 |
| DCV | = | Daclatasvir |
| DSV | = | Dasabuvir |
| DAA | = | Direct-acting antiviral |
| DDIs | = | Drug-drug interactions |
| EBR | = | Elbasvir |
| ESRD | = | End-stage renal disease |
| E1 | = | Envelope E1 glycoprotein |
| E2 | = | Envelope E2 glycoprotein |
| GT | = | Genotype |
| GECCO | = | German Hepatitis C Cohort |
| GLE | = | Glecaprevir |
| GZR | = | Grazoprevir |
| HBV | = | Hepatitis B |
| HBsAg | = | Hepatitis B virus surface antigen |
| HCV | = | Hepatitis C virus |
| CORE | = | Hepatitis C virus core protein |
| p7 | = | Hepatitis C virus viroporin p7 |
| HCC | = | Hepatocellular carcinoma |
| HIV | = | Human immunodeficiency virus |
| IFN | = | Interferon |
| LDV | = | Ledipasvir |
| MSM | = | Men Who Have Sex With Men |
| mITT | = | Modified intention-to-treat |
| NANBH | = | Non-a, Non- B hepatitis |
| NS2 | = | Non-structural 2 protein |
| NS3 | = | Non-structural 3 protein |
| NS3/4A | = | Non-structural 3/4A protein |
| NS4A | = | Non-structural 4A protein |
| NS4B | = | Non-structural 4B protein |
| NS5A | = | Non-structural 5A protein |
| NS5B | = | Non-structural 5B protein |
| NA | = | Nucleoside/nucleotide analogue |
| OBV | = | Ombitasvir |
| OATP1B | = | Organic anion transporting polypeptide 1B |
| PTV | = | Paritaprevir |
| Peg | = | Pegylated |
| PWID | = | People who inject drugs |
| PY | = | Person-years |
| P-gp | = | P-glycoprotein |
| PIB | = | Pibrentasvir |
| PIs | = | Protease inhibitors |
| HBVr | = | Reactivation of HBV |
| RWE | = | Real-world evidence |
| RAS | = | Resistance-associated substitutions |
| RBV | = | Ribavirin |
| RNA | = | Ribonucleic acid |
| PTV/r | = | Ritonavir-boosted paritaprevir |
| SMV | = | Simeprevir |
| SOF | = | Sofosbuvir |
| SVR | = | Sustained virological response |
| TVR | = | Telaprevir |
| TDF | = | Tenofovir disoproxil |
| AASLD | = | The American Association for the Study of Liver Disease |
| EASL | = | The European Association for the Study of the Liver |
| EMA | = | The European Medicines Agency |
| FDA | = | The Food and Drug Administration |
| T-ex | = | Treatment-experienced |
| T-naïve | = | Treatment-naïve |
| UTR | = | Untranslated region |
| VEL | = | Velpatasvir |
| VOX | = | Voxilaprevir |
| WHO | = | World Health Organization |
Declaration of Interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2024.2358139.