1Raghda Z Talaat, 2Desoky E Abou Ammo, 3Mona A. H. Shehata.
1Microbiology, 2Clinical Pathology, 3Tropical
Medicine Departments Tanta University.
In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell
damage are still poorly understood and both necrosis and apoptosis (programmed
cell death) may be operative. The study of the molecular mechanisms by which
liver injury is induced in HCV infection might lead to design new approaches by
which HCV infection can be controlled. In this work, we estimated hepatic
tissue expression of Fas(Apo-1/CD95) receptor at mRNA level as a main cell
death receptor that triggers apoptosis (using reverse transcription polymerase
chain reaction (RT-PCR), in relation to the measurement of serum soluble Fas
(sFas) that seems to inhibit apoptosis in vitro (using Enzyme Linked
Immunosorbent Assay (ELISA) ). The study was conducted on 59 HCV infected
patients included in three groups; chronic hepatitis (n=15) , liver cirrhosis
(n=30) and hepatocellular carcinoma (HCC) (n=14). In addition, ten apparently
healthy subjects served as controls. The results showed a significant increase
in tissue Fas mRNA and sFas in HCV infected patients groups as compared to
controls, with the highest values being found in HCC group. The liver cirrhosis
group, showed significant increase in hepatic expression of Fas mRNA (detected
in Child’s A cirrhotic patients) with no significant difference in serum sFas
values as compared to chronic hepatitis group. Hepatic expression of Fas mRNA
correlated significantly with serum sFas in HCV infected patients groups. In
chronic hepatitis patients both tissue Fas mRNA and serum sFas showed
significant positive correlation with the severity of necro inflammatory
activity grade, while no correlation was found with serum transaminases (ALT,
AST) in all patients groups. In cirrhotic patients serum sFas was increased in
accordance with the advance in Child’s grade (A, B, C,). Interestingly, it was
noticed that tissue Fas mRNA and serum sFas in HCV related HCC were
significantly decreased in grade III with poor cell differentiation compared to
grade IandII. It is concluded that Fas mediated apoptosis may play an important
role in the immune mediated liver cell injury in HCV infection, and this type
of reaction may occur in the absence of significant serum transaminases
elevation. Moreover, cancer cells in HCV related HCC at a low differentiation
level may escape from Fas mediated apoptosis.