<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Background</bold>: Severe complications of chronic hepatitis C – i.e. cirrhosis and hepatocellular carcinoma – are important causes of morbidity and mortality worldwide. Despite the overwhelming rates of sustained virologic response achieved after therapy with different combinations of direct-acting antiviral drugs (DAAs), treatment failure is still recorded, and is due to the mutations harboured by hepatitis C virus (HCV) resistance associated variants (RAVs) selected during therapy. Baseline RAVs testing was found significant for guiding treatment in the cases of treatment failure and, sometimes, in naïve patients.<bold>Methods</bold>: Romanian chronic hepatitis C patients unexposed to DAAs and infected with subtype 1b HCV were studied. Serum samples were used for Sanger population sequencing of a fragment containing NS3 viral protease, known to harbour resistance mutation against protease inhibitors (PIs).<bold>Results</bold>: Catalytic triad and zinc-binding site in the studied sequences were conserved. Low-intermediate resistance mutations to first generation PIs were detected either alone or in conjunction with resistance substitutions associated with second generation PIs. Cross-resistance and reduced susceptibility to certain DAAs were observed.<bold>Discussion</bold>: This study focused on HCV patients infected with subtype 1b strains, the most prevalent in Romania. The rate of RAVs found in this work is consistent with the results reported by similar studies from other countries. Noticeably, numerous polymorphisms of unknown significance to DAAs resistance, but reflecting the high genetic variability of HCV, were found in the studied sequences. Testing for RAVs can be a useful method for guiding treatment in a cost-efficient manner in developing countries where access to DAAs is limited.</abstract>

Background: Severe complications of chronic hepatitis C – i.e. cirrhosis and hepatocellular carcinoma – are important causes of morbidity and mortality worldwide. Despite the overwhelming rates of sustained virologic response achieved after therapy with different combinations of direct-acting antiviral drugs (DAAs), treatment failure is still recorded, and is due to the mutations harboured by hepatitis C virus (HCV) resistance associated variants (RAVs) selected during therapy. Baseline RAVs testing was found significant for guiding treatment in the cases of treatment failure and, sometimes, in naïve patients.Methods: Romanian chronic hepatitis C patients unexposed to DAAs and infected with subtype 1b HCV were studied. Serum samples were used for Sanger population sequencing of a fragment containing NS3 viral protease, known to harbour resistance mutation against protease inhibitors (PIs).Results: Catalytic triad and zinc-binding site in the studied sequences were conserved. Low-intermediate resistance mutations to first generation PIs were detected either alone or in conjunction with resistance substitutions associated with second generation PIs. Cross-resistance and reduced susceptibility to certain DAAs were observed.Discussion: This study focused on HCV patients infected with subtype 1b strains, the most prevalent in Romania. The rate of RAVs found in this work is consistent with the results reported by similar studies from other countries. Noticeably, numerous polymorphisms of unknown significance to DAAs resistance, but reflecting the high genetic variability of HCV, were found in the studied sequences. Testing for RAVs can be a useful method for guiding treatment in a cost-efficient manner in developing countries where access to DAAs is limited.

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Cantacuzino National Medico-Military Institute for Research and Development

Earth, Environmental and Life Sciences Division

The Research Institute of the University of Bucharest (ICUB)

“Dr Victor Babeş” Clinical Hospital for Infectious and Tropical Diseases

Revista Romana de Medicina de Laborator

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Background: Severe complications of chronic hepatitis C – i.e. cirrhosis and hepatocellular carcinoma – are important causes of morbidity and mortality...

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Online veröffentlicht: 29. Okt. 2018

Seitenbereich: 443 - 449

Eingereicht: 21. Mai 2018

Akzeptiert: 10. Juli 2018

DOI: https://doi.org/10.2478/rrlm-2018-0029

Schlüsselwörter
NS3 protease, direct-acting antivirals, resistance mutations, naïve to treatment patients

© 2018 Sorin Dinu et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Detection of anti-protease inhibitors resistance mutations in HCV strains infecting treatment-naïve chronic patients from Romania

Online veröffentlicht: 29. Okt. 2018

Seitenbereich: 443 - 449

Eingereicht: 21. Mai 2018

Akzeptiert: 10. Juli 2018

DOI: https://doi.org/10.2478/rrlm-2018-0029

SchlüsselwörterNS3 protease, direct-acting antivirals, resistance mutations, naïve to treatment patients

© 2018 Sorin Dinu et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Schlüsselwörter
NS3 protease, direct-acting antivirals, resistance mutations, naïve to treatment patients