4.6 Article

Changes in Autophagic Response in Patients with Chronic Hepatitis C Virus Infection

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AMERICAN JOURNAL OF PATHOLOGY
卷 178, 期 6, 页码 2708-2715

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2011.02.021

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  1. poste d'accueil INSERM
  2. Interface INSERM-AP-HP

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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 fund liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 ifnmunoblotting. 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. (Am J Pathol 2011, 178:2708-2715; DOI: 10.1016/j.ajpath.2011.02.021)

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