Evidences of Apoptosis in Hepatitis C Virus-Infected Hepatocytes and Peripheral Blood Monocuclear Cells in the Absence of Liver Injury

Abstract

Understanding the mechanism of Hepatitis C Virus (HCV) pathogenesis is an important part of HCV research. In this study, the presence of apoptosis in HCV-infected liver and Peripheral Blood Mononuclear Cells (PBMC) from patients positive for anti-HCV antibodies and negative for serum HCV-RNA was investigated. The samples obtained from 21 patients were studied by in situ Hybridization (ISH), Immunofluorescence, TUNEL reaction and caspase 3 activation assays. The findings show that both DNA fragmentation by TUNEL assay and activation of caspase 3 were detected in hepatocytes from patients histologically confirmed as bearing chronic hepatitis or with abnormal ALAT or GGTP as well as in patients with no histological evidences of chronic hepatitis and normalization of transaminases. Apoptotic cells were also detected in PBMC samples by the TUNEL assay. ISH analysis of liver biopsies and PBMC samples showed both positive and negative strands of the HCV genome localized in some cells showing nuclear characteristics of apoptosis such as chromatin margination, condensation and fragmentation. These typical morphological changes of apoptotic cell death were also observed in some hepatocytes showing reaction products suggestive of HCcAg. Data suggest that under certain conditions HCV induces apoptosis in the absence of liver injury. Induction of apoptosis in HCV-infected cells may interfere with viral replication, which may lead to undetectable levels of HCV-RNA in serum

Profile of expression of certain markers of apoptosis in chronic hepatitis C and hepatitis B patients in an Egyptian population

“…In addition, they observed a statistically significant increase in Bcl-2 expression in CHC patients without cirrhosis or ascites compared to healthy controls [39] . Falcon et al [40] detected DNA fragmentation by TUNEL assay and activation of caspase 3 in PBMCs and hepatocytes from patients with and without histological evidence of chronic hepatitis. The current study similarly found that the amount of apoptosis in cultured PBMCs (detected by acridine orange or Giemsa staining) from the CHB patient group was significantly higher than that of the control group (p \ 0.001) ( Table 5).…”

Hepatitis C Virus Core Protein Increases Expression of DR4 and DR5 in Peripheral Blood Mononuclear Cells

“…Thus, a reason for the significant increase in soluble TRAIL versus membrane-bound TRAIL is the body's needs to exert apoptotic activities locally and systemically to combat the effects of HCV infection. Falcόn et al, found that there was evidence of PBMC apoptosis in patients positive for anti-HCV antibodies [18]. However, this work suggested that apoptosis may be due to the Fas and tumor necrosis factor pathways of apoptosis.…”