Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs

Mélusine Durand, Nicolas Nagot, Quynh Bach Thi Nhu, Amélie Vizeneux, Linh Le Thi Thuy, Huong Thi Duong, Binh Nguyen Thanh, Delphine Rapoud, Roselyne Vallo, 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 LaureillardJean Pierre Molès

Research output: Contribution to journalArticlepeer-review

Abstract

People who inject drugs (PWID) are a population exposed to many genotoxicants and with a high prevalence of HCV infection. Direct-acting antiviral (DAA) regimens are now widely used to treat chronic HCV infection. Although side effects to treatment are currently rare, the long-term effects such as suspicions of de novo hepatocellular carcinoma (HCC) occurrence or HCC recurrence and cardiac defects are still up for debate. Given the structure of DAAs, the molecules have a potential mitochondrial DNA (mtDNA) genotoxicity. We have previously reported acute mtDNA toxicity of three DAA regimens among PWID with a strong impact on the rate of mtDNA deletion, less on the quantity of mtDNA copy per cell at sustained viral response at 12 weeks (SVR12). Herein, we report the mtDNA parameters nine months after drug discontinuation. We observed that the percentage of the deleted mtDNA genome increased over time. No exposure to any other genotoxicants during this period was associated with a high deletion percentage, suggesting that the replicative advantage of the deleted molecules outweighed their elimination processes. Such observation calls for longer-term follow-up and may contribute to the molecular basis of subclinical side effects of DAA treatments.

Original languageEnglish (US)
Article number2541
JournalBiomedicines
Volume10
Issue number10
DOIs
StatePublished - Oct 2022

Keywords

  • DAA
  • genotoxicity
  • HCV
  • mitochondria
  • side effect

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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