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 hepatitis and cirrhosis, playing a promoting role in the multistep process of hepatocarcinogenesis by maintaining liver inflammation, hepatocyte necrosis and regeneration. The aim of this study was to measure the DNA ploidy and cell proliferation of hepatocytes in patients with chronic hepatitis C. Hepatocyte nucleus suspension was analyzed from 45 patients with chronic hepatitis C and from 27 patients with chronic hepatitis non-C. The histopathological pattern of chronic hepatitis samples/grade, stage/was investigated. A significantly lower cyclin A protein expression and cytometrically measured S-phase fraction was observed in chronic hepatitis C as compared to chronic hepatitis non-C, representing suppressed cell proliferation of virus infected cells. In the chronic hepatitis C groups, the S-phase fraction depression was moderate, the grade of inflammation and cyclin A protein expression were also decreased, mainly in the severe grade group. In chronic hepatitis 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 cellular 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 that in chronic viral hepatitis C, the hepatocyte proliferation is suppressed parallel with the degree of inflammation, while the DNA content becomes aneuploid. The aneuploidy is a sign of genetic instability, predisposing the affected cells to unbalanced chromosomal abnormality which finally leads to malignant transformation.
Werling
K
K
Second Department of Internal Medicine, Joint Research University of the Hungarian Academy of Sciences, Budapest, Hungary.
Szepesi
A
A
Szentirmay
Z
Z
Schaff
Z
Z
Tulassay
Z
Z
Szalay
F
F
D000704:Analysis of Variance; D001706:Biopsy; D002455:Cell Division / Q000502:physiology; D019925:Cyclin A / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D016174:Hepacivirus / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011003:Ploidies; D012044:Regression Analysis
D019925:Cyclin A; D004247:DNA