HEPATOCELLULAR PROLIFERATION, TNF-ALPHA AND INFLAMMATION IN PRIMARY BILIARY-CIRRHOSIS (PBC)

The aims of this study were to investigate the rate of hepatocellular proliferation in PBC and its correlation with the site of inflammation and serum TNFalpha levels. Hepatic proliferation was evaluated in liver sections from 11 patients with PBC (two histological stage II, eight stage III, one stage IV) using the indirect immunoperoxidase technique with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). Counter-staining with hematoxylin was performed and at least 500 nuclei were counted by two observers who blindly calculated the site of positive cells (perivenular, periportal/periseptal). The percentage of hepatocytes expressing PCNA was significantly higher in the periportal/periseptal regions than in the perivenular area (70 +/- 5.8% vs. 36 +/- 6.9%, P < 0.002). Hepatocellular PCNA expression in the periportal/periseptal (portal area) correlated with TNFalpha serum levels (r = 0.8, P < 0.03). In conclusion, hepatocellular proliferation in PBC significantly correlates with the site of inflammation and serum levels of TNFalpha. This data seems to confirm that inflammation and cytokines may stimulate hepatocyte DNA synthesis.