title: Changes in autophagic response in patients with chronic hepatitis C virus infection.
abstract: Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B virus infection, and 21 with no or mild liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 immunoblotting. Using light chain 3 immunoblotting, the form present on autophagic vesicle (light chain 3-II) was significantly higher in CHC patients than in controls (P < 0.05). Using quantitative electron microscopy analysis, the median number of autophagic vesicles observed in hepatocytes from CHC patients was sixfold higher than in overall controls (P < 0.001). In contrast, there was no difference between CHC patients and controls in the number of mature lysosomes with electron-dense contents arguing in favor of a lack of fusion between autophagosome and lysosome. Neither genotype nor viral load influenced the autophagy level. In conclusion, autophagy is altered in hepatocytes from CHC patients, likely due to a blockade of the last step of the autophagic process.
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. perautou@yahoo.fr
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Rautou
authors.forename: Dominique
authors.initials: D
authors.lastname: Cazals-Hatem
authors.forename: Gérard
authors.initials: G
authors.lastname: Feldmann
authors.forename: Abdellah
authors.initials: A
authors.lastname: Mansouri
authors.forename: Alain
authors.initials: A
authors.lastname: Grodet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Barge
authors.forename: Michèle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.forename: Aurélie
authors.initials: A
authors.lastname: Duces
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Dominique
authors.initials: D
authors.lastname: Valla
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
mesh_terms: D000328:Adult; D000368:Aged; D001343:Autophagy; D016022:Case-Control Studies; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology*; D022781:Hepatocytes / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins