Apoptosis pathway of liver cells in chronic hepatitis

To study the pathway of apoptosis in chronic liver disease and the role of mitochondria in programmed cell death.

Liver biopsy specimens from 72 cases of chronic hepatitis and 29 cases of post hepatitis cirrhosis were studied. The pro-apoptotic protein Fas, FasL, Bax and the anti-apoptotic protein Bcl-2, Bcl-x(L), Bcl-2 alpha were studied immunohistochemically by SP method. Specimens from 15 cases of chronic hepatitis and post hepatitis cirrhosis were examined for their ultramicrostructures with special attention to their mitochondrial changes. Specimens from 3 normal adults (demised in traffic accidents) were used as control.

The expression of proapoptotic proteins (Fas, FasL, Bax) in hepatocytes was significantly higher in the chronic hepatitis group than in the cirrhosis group (P<0.001). In the study of ultramicrostructure 364 hepatocytes were examined, from 12 cases of chronic hepatitis (including 10 mild cases, 1 moderate case and 1 severe case). Out of 364 hepatocytes 40 (11.0%) hepatocytes were found with various kinds of destruction in their mitochondria. Rupture of the outer membrane of mitochondria and the leakage of matrix from the intermembrane space were definitely demonstrated. The ultramicrostructural changes of mitochondria in the chronic hepatitis group were statistically higher than that in normal adults control group (chi(2)=4.32, P<0.05).

The result of the study was in support of the current view that the apoptotic process in chronic hepatitis patients were largely along the intrinsic pathway (mitochondrial pathway), given that the intrinsic and extrinsic pathways could interlinked (converged) at some point on their progression, also it is impossible at present to exclude the possibility that the two pathways could be chosen by hepatocytes in parallel simultaneously.