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Published on: June 9, 2022
Naturally occurring NS3 resistance-associated variants in hepatitis C virus genotype 1: Their relevance for
Natalia Echeverría1, Gabriela Betancour1, Fabiana Gámbaro1
1Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay.
Insights
Naturally occurring Hepatitis C virus (HCV) resistance mutations were found in a significant number of treatment-naïve Uruguayan patients. Identifying these baseline resistance-associated variants (RAVs) is crucial for predicting treatment outcomes.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- Hepatitis C virus (HCV) infection affects millions globally, causing chronic liver disease, cirrhosis, and liver cancer.
- Current treatments, including direct-acting antiviral agents (DAAs), face challenges due to viral variability and resistance.
- Resistance-associated variants (RAVs) present before treatment can impact therapeutic success.
Purpose of the Study:
- To investigate the prevalence of RAVs in the NS3 serine protease region of HCV in treatment-naïve Uruguayan patients.
- To compare these findings with data from other South American countries.
- To assess the clinical significance of baseline RAVs for patient management and outcome prediction.
Main Methods:
- Analysis of a cohort of Uruguayan patients with chronic hepatitis C.
- Genotyping of HCV and sequencing of the NS3 serine protease region.
- Comparison of mutation frequencies with existing South American data.
Main Results:
- Naturally occurring mutations conferring resistance to NS3 protease inhibitors were detected in a substantial proportion of Uruguayan patients infected with HCV genotype 1.
- The prevalence of these baseline RAVs was analyzed and compared regionally.
- Findings highlight the presence of pre-existing resistance in DAA-naïve populations.
Conclusions:
- Baseline RAVs in the HCV NS3 protease region are present in a significant percentage of treatment-naïve patients in Uruguay.
- Identifying these variants is critical for optimizing HCV treatment strategies and predicting patient outcomes in developing countries.
- Further regional surveillance is warranted to understand the full scope of HCV resistance in South America.
Abstract:
Hepatitis C virus (HCV) is a major cause of global morbidity and mortality, with an estimated 130-150 million infected individuals worldwide. HCV is a leading cause of chronic liver diseases including cirrhosis and hepatocellular carcinoma. Current treatment options in developing countries involve pegylated interferon-α and ribavirin as dual therapy or in combination with one or more direct-acting antiviral agents (DAA). The emergence of resistance-associated variants (RAVs) after treatment reveals the great variability of this virus leading to a great difficulty in developing effective antiviral strategies. Baseline RAVs detected in DAA treatment-naïve HCV-infected patients could be of great importance for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS3 protease inhibitor mutations has been addressed in many countries, there are only a few reports on their prevalence in South America. In this study, we investigated the presence of RAVs in the HCV NS3 serine protease region by analysing a cohort of Uruguayan patients with chronic hepatitis C who had not been treated with any DAAs and compare them with the results found for other South American countries. The results of these studies revealed that naturally occurring mutations conferring resistance to NS3 inhibitors exist in a substantial proportion of Uruguayan treatment-naïve patients infected with HCV genotype 1 enrolled in these studies. The identification of these baseline RAVs could be of great importance for patients' management and outcome prediction in developing countries.
