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.

Synectin promotes fibrogenesis by regulating PDGFR isoforms through distinct mechanisms

“…Alcoholic cirrhosis (n = 6) (22-24), including nonalcoholic fatty liver disease (25), chronic hepatitis C infection (26), and acetaminophen toxicity (27). However, autophagy has also been shown to increase in HSC during activation (22,28,29).…”

Target of Rapamycin (TOR) and Autophagy in Chronic Hepatitis C Virus Infection: Relation to Disease Activity

“…Limited studies with similar results evaluated autophagy in patients with chronic HCV infection [69,70]. However, in experimental studies autophagy was activated in HCV-RNA expressing cultured cells [71][72][73][74].…”

Autophagy Modulation As a Potential Therapeutic Target for Liver Diseases

“…67 Studies have shown that there is an accumulation of autophagic vacuoles in HCV-infected hepatocytes; however this autophagy is inefficient as the autophagosomes are not able to increase autophagic protein degradation. The strategies used by HCV to evade and take advantage of autophagy for its replication are: (i) HCV avoids recognition by the autophagic process with rare or no co-localization of HCV proteins in autophagic vacuoles [68][69][70] ;…”

“…(ii) HCV prevents maturation of autophagosomes into autolysosomes 68,69 ; and (iii) HCV utilizes components of autophagy to enhance intracellular replication. The autophagy proteins are likely to be proviral factors for the initial steps of HCV replication.…”

“…The autophagy proteins are likely to be proviral factors for the initial steps of HCV replication. [67][68][69] The autophagy machinery is also subverted in HBV. The autophagosomes are also induced in HBV; but, unlike HCV, the late autophagic vacuoles are detectable in hepatocytes.…”