Effect of hepatitis C virus on hepatocyte proliferation and DNA ploidy in patients with chronic hepatitis C

Hepatitis C virus infection may act as a cofactor by inducing chronic hepat itis and cirrhosis, playing a promoting role in the multistep process of he patocarcinogenesis by maintaining liver inflammation, hepatocyte necrosis a nd regeneration. The aim of this study was to measure the DNA ploidy and ce ll proliferation of hepatocytes in patients with chronic hepatitis C. Hepatocyte nucleus suspension was analyzed from 45 patients with chronic he patitis C and from 27 patients with chronic hepatitis non-C. The histopatho logical pattern of chronic hepatitis samples/grade, stage/was investigated. A significantly lower cyclin A protein expression and cytometrically measur ed S-phase fraction was observed in chronic hepatitis Cas compared to chron ic hepatitis non-C, representing suppressed cell proliferation of virus inf ected cells. In the chronic hepatitis C groups, the S-phase fraction depres sion was moderate, the grade of inflammation and cyclin A protein expressio n were also decreased, mainly in the severe grade group. In chronic hepatit is non-C, the number of cyclin A staining-positive cells increased parallel with severity of the inflammation. In addition, the HCV infection caused a near diploid minimally aneuploid ce llular DNA content in the cases of moderate and severe histological groups. In contrast, the cellular DNA content was consequently diploid-independent of histological grades in chronic hepatitis non-C. Our results suggest tha t in chronic viral hepatitis C, the hepatocyte proliferation is suppressed parallel with the degree of inflammation, while the DNA content becomes ane uploid. The aneuploidy is a sign of genetic instability, predisposing the a ffected cells to unbalanced chromosomal abnormality which finally leads to malignant transformation.