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Road to elimination of HCV: Clinical challenges in HCV management
C Nelson Hayes1,2, Michio Imamura1,2, Junko Tanaka2,3
1Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Insights
Direct-acting antiviral therapies achieve high hepatitis C virus (HCV) cure rates, but some patients fail treatment. Identifying and treating all infections is crucial for HCV elimination.
Area of Science:
- Hepatology
- Virology
- Infectious Diseases
Background:
- Hepatitis C virus (HCV) infection has seen significant treatment advancements since its 1989 discovery.
- Direct-acting antiviral (DAA) therapies now offer high sustained virological response (SVR) rates, exceeding 98% in most patients.
- Treatment is effective even for patients with prior treatment failures, resistance-associated substitutions (RASs), or compensated cirrhosis.
Purpose of the Study:
- To review the efficacy and limitations of current direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV).
- To discuss reasons for treatment failure and alternative therapeutic strategies.
- To highlight the importance of diagnosing and treating undiagnosed HCV infections for eventual virus elimination.
Main Methods:
- Review of current direct-acting antiviral (DAA) combination therapies (e.g., glecaprevir/pibrentasvir, velpatasvir/sofosbuvir).
- Analysis of treatment outcomes, including sustained virological response (SVR) rates and adverse events.
- Examination of challenges in HCV treatment scale-up and the significance of undiagnosed infections.
Main Results:
- DAA therapies achieve high SVR rates (98%), with rare or mild adverse events.
- A small subset of patients fail DAA therapy, sometimes due to NS5A P32 deletion mutants in genotype 1b HCV.
- Alternative treatments like sofosbuvir plus ribavirin can be used for treatment failures.
Conclusions:
- Current DAA therapies are highly effective for hepatitis C virus (HCV) treatment, but challenges remain.
- Identifying and treating undiagnosed HCV infections is essential for long-term disease management and virus elimination.
- Screening high-risk populations and considering the cost-effectiveness of treatment are vital for public health strategies.
Abstract:
Since its discovery in 1989, the road to a cure for hepatitis C virus (HCV) has been slow, but most patients can now expect to achieve a sustained virological response (SVR). With direct-acting antiviral (DAA) combination therapies such as glecaprevir/pibrentasvir and velpatasvir/sofosbuvir, 98% of patients successfully eradicate the virus, even if previous treatments failed or if resistance-associated substitutions (RASs) are present. Adverse events are rare or mild, and patients with compensated cirrhosis and other co-morbidities are often eligible for treatment. However, a small number of patients fail to eradicate the virus even after retreatment. The cause of failure is mainly due to emergence of NS5A P32 deletion mutants after initial DAA therapy in genotype 1b patients, although the reason is unknown for some patients. Alternative therapies that do not rely on NS5A inhibitors, such as sofosbuvir plus ribavirin, can be attempted in these patients. While scaled-up treatment efforts present a challenge, another problem is that many carriers are unaware of their infection. Long-term damage to the liver becomes irreversible, and patients who are not diagnosed in time can develop liver cancer or liver failure even after eliminating the virus. The long-term costs of treatment of advanced liver disease in undiagnosed patients relative to the immediate costs of DAA therapy should be considered. As no vaccine is yet available, eventual elimination of the virus requires identifying and treating undiagnosed cases and screening of high-risk populations such as injection drug users and men who have sex with men and female sex workers.
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