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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
New approaches in the treatment of hepatitis C
Rocío González-Grande1, Miguel Jiménez-Pérez1, Carolina González Arjona1
1Rocío González-Grande, Miguel Jiménez-Pérez, González Arjona, José Mostazo Torres, Liver Transplantation and Hepatology Unit, UGC de Aparato Digestivo, Hospital Regional Universitario, 29010 Malaga, Spain.
Insights
New direct-acting antiviral agents (DAA) offer improved hepatitis C virus (HCV) treatment, achieving high sustained viral response rates. Real-world data on side effects and special populations are needed to guide DAA therapy.
Area of Science:
- Hepatology
- Virology
- Pharmacology
Background:
- Chronic hepatitis C virus (HCV) infection affects millions globally, leading to significant liver-related morbidity and mortality.
- Traditional pegylated interferon and ribavirin (PEG/RBV) therapy showed limited efficacy, especially for genotypes 1 and 4.
- Early direct-acting antiviral agents (DAA) improved outcomes but presented toxicity and cost challenges.
Purpose of the Study:
- To review the evolution of hepatitis C virus (HCV) antiviral treatment strategies.
- To highlight the advantages and limitations of new direct-acting antiviral agents (DAA).
- To emphasize the need for real-world data collection and patient prioritization for DAA therapy.
Main Methods:
- Review of historical and current HCV treatment guidelines and clinical trial data.
- Analysis of efficacy, safety, and tolerability of different antiviral regimens.
- Discussion of the impact of new DAAs on clinical practice and patient management.
Main Results:
- Newer DAAs demonstrate significantly higher sustained viral response (SVR) rates, up to 100%, with improved tolerance and shorter treatment durations.
- DAA regimens are largely free of PEG/RBV, enabling broader patient applicability.
- Despite high efficacy, limited real-world data exist on side effects, drug interactions, and use in special populations or uncommon genotypes.
Conclusions:
- Modern DAAs have revolutionized HCV treatment, offering highly effective and well-tolerated options.
- The high cost of DAAs necessitates careful patient selection and prioritization.
- Implementation of patient registries is crucial for gathering real-world evidence on DAA effectiveness, safety, and optimal use in diverse clinical settings.
Abstract:
About 130-170 million people, is estimated to be infected with the hepatitis C virus (HCV). Chronic HCV infection is one of the leading causes of liver-related death and in many countries it is the primary reason for having a liver transplant. The main aim of antiviral treatment is to eradicate the virus. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin (PEG/RBV). However, in genotypes 1 and 4 the rates of viral response did not surpass 50%, reaching up to 80% in the rest. In 2011 approval was given for the first direct acting antiviral agents (DAA), boceprevir and telaprevir, for treatment of genotype 1, in combination with traditional dual therapy. This strategy managed to increase the rates of sustained viral response (SVR) in both naive patients and in retreated patients, but with greater toxicity, interactions and cost, as well as being less safe in patients with advanced disease, in whom this treatment can trigger decompensation or even death. The recent, accelerated incorporation since 2013 of new more effective DAA, with pan-genomic properties and excellent tolerance, besides increasing the rates of SVR (even up to 100%), has also created a new scenario: shorter therapies, less toxicity and regimens free of PEG/RBV. This has enabled their almost generalised applicability in all patients. However, it should be noted that most of the scientific evidence available is based on expert opinion, case-control series, cohort studies and phase 2 and 3 trials, some with a reduced number of patients and select groups. Few data are currently available about the use of these drugs in daily clinical practice, particularly in relation to the appearance of side effects and interactions with other drugs, or their use in special populations or persons with the less common genotypes. This situation suggests the need for the generalised implementation of registries of patients receiving antiviral therapy. The main inconvenience of these new drugs is their high cost. This necessitates selection and prioritization of candidate patients to receive them, via strategies established by the various national organs, in accordance with the recommendations of scientific societies.
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