| Title: |
Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis |
| Authors: |
Loureiro, Dimitri; Tout, Issam; Narguet, Stéphanie; Bed, Cheikh Mohamed; Roinard, Morgane; Sleiman, Ahmad; Boyer, Nathalie; Pons-Kerjean, Nathalie; Castelnau, Corinne; Giuly, Nathalie; Tonui, Dorothy; Soumelis, Vassili; El-Benna, Jamel; Soussan, Patrick; Moreau, Richard; Paradis, Valérie; Mansouri, Abdellah; Asselah, Tarik |
| Contributors: |
Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Hôpital Beaujon AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hopital Saint-Louis AP-HP (AP-HP); Centre d'Immunologie et des Maladies Infectieuses (CIMI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 0270-9139. |
| Publisher Information: |
CCSD; Wiley-Blackwell |
| Publication Year: |
2022 |
| Subject Terms: |
Hepatitis B virus; Mitochondrial dysfunctions; Inflammation; Mitochondrial DNA; Mitochondrial unfolded protein response; Reactive oxygen species; Mitophagy; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology |
| Description: |
International audience ; Background and Aims: Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters mitochondria in experimental models. Our goal was to investigate whether HBV might alter liver mitochondria also in humans, and the resulting mitochondrial stress might account for the progression of fibrosis in chronic hepatitis B (CHB).Approach and Results: The study included 146 treatment-naïve CHB mono-infected patients. Patients with CHB and advanced fibrosis (AF) or cirrhosis (F3-F4) were compared to patients with no/mild-moderate fibrosis (F0-F2). Patients with CHB were further compared to patients with chronic hepatitis C (CHC; n = 33), nonalcoholic steatohepatatis (NASH; n = 12), and healthy controls (n = 24). We detected oxidative damage to mitochondrial DNA (mtDNA), including mtDNA strand beaks, and identified multiple mtDNA deletions in patients with F3-F4 as compared to patients with F0-F2. Alterations in mitochondrial function, mitochondrial unfolded protein response, biogenesis, mitophagy, and liver inflammation were observed in patients with AF or cirrhosis associated with CHB, CHC, and NASH. In vitro, significant increases of the mitochondrial formation of superoxide and peroxynitrite as well as mtDNA damage, nitration of the mitochondrial respiratory chain complexes, and impairment of complex I occurred in HepG2 cells replicating HBV or transiently expressing hepatitits B virus X protein. mtDNA damage and complex I impairment were prevented with the superoxide-scavenging Mito-Tempo or with inducible nitric oxide synthase (iNOS)–specific inhibitor 1400 W.Conclusions: Our results emphasized the importance of mitochondrial OS, mtDNA damage, and associated alterations in mitochondrial function and dynamics in AF or cirrhosis in CHB and NASH. Mitochondria might be a target in drug development to stop fibrosis progression. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/hep.32731 |
| Availability: |
https://hal.science/hal-03830813; https://hal.science/hal-03830813v1/document; https://hal.science/hal-03830813v1/file/HEP-21-2028.R1_Loureiro%20et%20al.%20Main%20text.pdf; https://doi.org/10.1002/hep.32731 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.AD540B83 |
| Database: |
BASE |