Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs

Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug expos...

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Autores principales:	Mélusine Durand, Nicolas Nagot, Quynh Bach Thi Nhu, Roselyne Vallo, Linh Le Thi Thuy, Huong Thi Duong, Binh Nguyen Thanh, Delphine Rapoud, Catherine Quillet, Hong Thi Tran, Laurent Michel, Thanh Nham Thi Tuyet, Oanh Khuat Thi Hai, Vinh Vu Hai, Jonathan Feelemyer, Philippe Vande Perre, Don Des Jarlais, Khue Pham Minh, Didier Laureillard, Jean-Pierre Molès
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mitochondria genotoxicity HCV treatment drug users Medicine R
Acceso en línea:	https://doaj.org/article/06bf158bdd364d42a3e099970d19822a
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spelling	oai:doaj.org-article:06bf158bdd364d42a3e099970d19822a2021-11-11T17:29:42ZMitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs10.3390/jcm102148242077-0383https://doaj.org/article/06bf158bdd364d42a3e099970d19822a2021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/4824https://doaj.org/toc/2077-0383Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treatment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and therefore call for a long-term follow-up.Mélusine DurandNicolas NagotQuynh Bach Thi NhuRoselyne ValloLinh Le Thi ThuyHuong Thi DuongBinh Nguyen ThanhDelphine RapoudCatherine QuilletHong Thi TranLaurent MichelThanh Nham Thi TuyetOanh Khuat Thi HaiVinh Vu HaiJonathan FeelemyerPhilippe Vande PerreDon Des JarlaisKhue Pham MinhDidier LaureillardJean-Pierre MolèsMDPI AGarticlemitochondriagenotoxicityHCV treatmentdrug usersMedicineRENJournal of Clinical Medicine, Vol 10, Iss 4824, p 4824 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondria genotoxicity HCV treatment drug users Medicine R
spellingShingle	mitochondria genotoxicity HCV treatment drug users Medicine R Mélusine Durand Nicolas Nagot Quynh Bach Thi Nhu Roselyne Vallo Linh Le Thi Thuy Huong Thi Duong Binh Nguyen Thanh Delphine Rapoud Catherine Quillet Hong Thi Tran Laurent Michel Thanh Nham Thi Tuyet Oanh Khuat Thi Hai Vinh Vu Hai Jonathan Feelemyer Philippe Vande Perre Don Des Jarlais Khue Pham Minh Didier Laureillard Jean-Pierre Molès Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs
description	Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treatment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and therefore call for a long-term follow-up.
format	article
author	Mélusine Durand Nicolas Nagot Quynh Bach Thi Nhu Roselyne Vallo Linh Le Thi Thuy Huong Thi Duong Binh Nguyen Thanh Delphine Rapoud Catherine Quillet Hong Thi Tran Laurent Michel Thanh Nham Thi Tuyet Oanh Khuat Thi Hai Vinh Vu Hai Jonathan Feelemyer Philippe Vande Perre Don Des Jarlais Khue Pham Minh Didier Laureillard Jean-Pierre Molès
author_facet	Mélusine Durand Nicolas Nagot Quynh Bach Thi Nhu Roselyne Vallo Linh Le Thi Thuy Huong Thi Duong Binh Nguyen Thanh Delphine Rapoud Catherine Quillet Hong Thi Tran Laurent Michel Thanh Nham Thi Tuyet Oanh Khuat Thi Hai Vinh Vu Hai Jonathan Feelemyer Philippe Vande Perre Don Des Jarlais Khue Pham Minh Didier Laureillard Jean-Pierre Molès
author_sort	Mélusine Durand
title	Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs
title_short	Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs
title_full	Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs
title_fullStr	Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs
title_full_unstemmed	Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs
title_sort	mitochondrial genotoxicity of hepatitis c treatment among people who inject drugs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/06bf158bdd364d42a3e099970d19822a
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Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs

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