LC3-Associated Phagocytosis in Hepatitis C Virus-Induced Fibrosis

During LC3-associated phagocytosis (LAP), a non-canonical form of autophagy, LC3 is recruited to pathogen and apoptotic cells containing phagosomes, where the phagocytosed cargo is degraded. Given the importance of LAP in host defense and the role of phagocytic cells in liver inflammation and fibrosis, this study assessed LAP in peripheral blood neutrophils and monocytes from patients with variable degrees of liver fibrosis and cirrhosis secondary to viral hepatitis C infection. LAP was quantified by flow cytometry using labeled zymosan as a stimulus to engage LAP and LC3 antibodies to detect LC3 recruitment. LAP engagement was evaluated as the integrated mean fluorescence intensity of LC3 in zymosan-positive cells. LAP was enhanced in patients with mild to moderate liver fibrosis (stages F1-F2) compared with patients with no fibrosis (F0) and severe fibrosis or cirrhosis (stages F3-F4). Furthermore, LAP in both neutrophils and monocytes correlated with the stage of fibrosis from F0 to F2, indicating that as the process of fibrosis progressed in the early stages, LAP activity increased. No differences in LAP were observed between treatment-naïve and those who received direct acting antiviral therapy and achieved sustained virologic response (SVR), suggesting that the process of fibrosis had a more significant impact on LAP, rather than the presence or absence of HCV infection. In conclusion, LAP is enhanced in circulating phagocytes during early stages of HCV-related fibrosis but declines in advanced disease, independent of treatment status and SVR.