Imbalance between cytoproliferation and apoptosis in hepatitis C virus related chronic liver disease

An imbalance between cytoproliferation and apoptosis may be relevant in liv er carcinogenesis. The aim of this study was to analyse these parameters in patients with chronic liver damage in relation to the aetiology of the dis ease. Forty-eight patients were studied: 23 had hepatitis C virus (HCV)- an d 11 had hepatitis B virus (HBV)-related chronic hepatitis, seven had alcoh olic liver disease, and seven had haemochromatosis. The biopsies were used for routine diagnosis, cytoproliferative indexing (MIB1, Ki67 monoclonal an tibody), apoptosis (APO, in situ end labelling) and, in part, liver iron an d malondialdehyde determination. Apoptosis was similar in all patient subgr oups and correlated with hepatitis grading (P=0.002) and ALT levels (P=0.00 4); cytoproliferation (MIB1) levels were higher in HCV patients, both as a whole and in the periportal area (P=0.02 and P=0.03). MIB1 correlated with ALT levels (P=0.0001), hepatitis grading (P=0.02) and tissue iron (P=0.04). APO and MIB1 were higher in patients with than in those without cirrhosis (P=0.0006 and P=0.03, respectively). APO correlated with MIB1 (P=0.001), ov erall but not in HCV patients. The MIB1/APO ratio was significantly higher in HCV patients than in the other groups (P=0.02). In summary, cytoprolifer ation is more pronounced in chronic HCV-related hepatitis, while APO is not significantly higher than in other types of liver damage, suggesting an im balance between the two. APO and MIB1 are directly related to the extent of liver damage and, from a biochemical point of view, to tissue iron levels.