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Apoptotic cell death does not parallel other indicators of liver damage in chronic hepatitis C patients
C M Rodrigues1, D Brites, F Serejo
1Centro de Patog¿enese Molecular, Faculdade de Farm¿acia, University of Lisbon, Portugal.
Insights
Hepatitis C virus (HCV) infection's impact on liver health is complex. This study found increased apoptosis in early stages of chronic hepatitis C, suggesting a role in disease progression and potential links to hepatocellular dysplasia in advanced stages.
Area of Science:
- Hepatology
- Virology
- Cell Biology
Background:
- Mechanisms of hepatocyte damage in chronic Hepatitis C Virus (HCV) infection are not fully understood.
- In vitro studies suggest HCV core protein may disrupt apoptosis signaling pathways.
- Chronic liver disease progression in HCV requires further investigation into cellular damage mechanisms.
Purpose of the Study:
- Determine the extent of apoptosis in the liver of patients with chronic HCV infection.
- Evaluate correlations between clinical/biochemical data and histological findings.
- Investigate the relationship between apoptosis and histological disease activity.
Main Methods:
- Included twelve patients with chronic hepatitis C.
- Assessed liver histology using the Knodell Histological Activity Index (HAI).
- Quantified DNA fragmentation via TUNEL assay and measured bile acids.
Main Results:
- Patients with lower HAI scores (less severe disease) exhibited significantly higher rates of apoptosis compared to those with higher HAI scores or controls.
- Elevated levels of toxic bile acids were observed in patients compared to controls.
- Chenodeoxycholic acid levels were slightly higher in serum and liver of patients with less severe disease.
Conclusions:
- Less severe chronic hepatitis C is associated with increased apoptosis, potentially influenced by chenodeoxycholic acid levels.
- A reduced apoptotic rate in advanced liver disease may correlate with the incidence of hepatocellular dysplasia/neoplasia.
- Apoptosis plays a complex role in the pathogenesis of chronic HCV infection.
Abstract:
The mechanisms of hepatocyte damage and the events that lead to high rates of chronic liver disease in hepatitis C virus (HCV) infection remain unclear. Recent in vitro studies have suggested that the HCV core protein may disrupt specific signalling pathways of apoptosis. This prompted us to study patients with chronic HCV infection to: determine the extent of apoptosis in the liver; evaluate whether clinical and biochemical data are correlated with histological findings; and to investigate if apoptosis is related to the histological activity of the disease. Twelve patients with chronic hepatitis C were included in the study. Liver histology was scored by using the histological activity index (HAI) of Knodell et al. DNA fragmentation was assessed in liver tissue by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) assay. Routine methods were used to determine serum markers of liver disease. Bile acids were measured in serum and liver by gas chromatography. Patients were placed, according to their HAI score, into group A (3.8 +/- 0.3) or group B (7.8 +/- 0.8) (P < 0.01). Liver enzymes tended to be higher in group B patients than in patients of group A. Levels of toxic bile acids in serum were greater in patients than in controls (P < 0.01). Chenodeoxycholic acid values were slightly higher in serum and liver of patients in group A. Liver biopsies with low HAI scores showed an increased rate of apoptosis (18.0 +/- 4.0 apoptotic cells per field) compared to those with higher HAI scores (6.6 +/- 2.1, P < 0.05) or to controls (3.5 +/- 0.4, P < 0.01). Hence, less severe liver disease, associated with lower histological grades and biochemistries, as well as increased levels of chenodeoxycholic acid, induces an expanded apoptotic response. The lower apoptotic rate in advanced liver disease may be associated with the high incidence of hepatocellular dysplasia/neoplasia.
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