Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs

被引：3

作者：

Durand, Melusine ^{[1
]}

Nagot, Nicolas ^{[1
]}

Nhu, Quynh Bach Thi ^{[2
]}

Vallo, Roselyne ^{[1
]}

Thuy, Linh Le Thi ^{[2
]}

Duong, Huong Thi ^{[2
]}

Thanh, Binh Nguyen ^{[2
]}

Rapoud, Delphine ^{[1
]}

Quillet, Catherine ^{[1
]}

Tran, Hong Thi ^{[2
]}

Michel, Laurent ^{[3
]}

Tuyet, Thanh Nham Thi ^{[4
]}

Hai, Oanh Khuat Thi ^{[4
]}

Hai, Vinh Vu ^{[5
]}

Feelemyer, Jonathan ^{[6
]}

Vande Perre, Philippe ^{[1
]}

Jarlais, Don Des ^{[6
]}

Minh, Khue Pham ^{[2
]}

Laureillard, Didier ^{[1
,7
]}

Moles, Jean-Pierre ^{[1
]}

机构：

[1] Univ Antilles, Pathogenesis & Control Chron & Emerging Infect, Univ Montpellier, INSERM,EFS, F-34394 Montpellier, France

[2] Hai Phong Univ Med & Pharm, Fac Publ Hlth, Haiphong 04212, Vietnam

[3] Pierre Nicole Ctr, Paris Saclay, CESP UMR1018, French Red Cross, F-75005 Paris, France

[4] Supporting Community Dev Initiat, Hanoi 11513, Vietnam

[5] Viet Tiep Hosp, Infect & Trop Dis Dept, Haiphong 04708, Vietnam

[6] NYU, Sch Global Publ Hlth, New York, NY 10003 USA

[7] Caremeau Univ Hosp, Infect & Trop Dis Dept, F-30029 Nimes, France

来源：

JOURNAL OF CLINICAL MEDICINE | 2021年 / 10卷 / 21期

基金：

美国国家卫生研究院;

关键词：

mitochondria; genotoxicity; HCV treatment; drug users; DNA COPY NUMBER; RNA-POLYMERASE; HIV-INFECTION; TOXICITY; METHADONE;

D O I：

10.3390/jcm10214824

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：12

共 41 条

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