Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis

Background and aim: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. Methods: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. Results: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis ( low activity: 75.1 (18.8)% v high activity: 61.8 (21.6)%, p = 0.0111, and low fibrosis: 77.3 (13.8)% v high fibrosis: 57.4 (23.3)%, p = 0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis ( low activity: 11.9 (15.5)% v high activity: 22.2 (20.1)%, p = 0.0166, and low fibrosis: 9.4 (10.7)% v high fibrosis: 26.4 ( 21.6)%, p = 0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections ( HBV: 18.2 (7.6)% v HCV: 12.0 (4.8)%; p = 0.0020). Under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction ( p = 0.0294). Conclusion: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.