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

An imbalance between cytoproliferation and apoptosis may be relevant in liver carcinogenesis. The aim of this study was to analyse these parameters in patients with chronic liver damage in relation to the aetiology of the disease. Forty-eight patients were studied: 23 had hepatitis C virus (HCV)- and 11 had hepatitis B virus (HBV)-related chronic hepatitis, seven had alcoholic liver disease, and seven had haemochromatosis. The biopsies were used for routine diagnosis, cytoproliferative indexing (MIB1, Ki67 monoclonal antibody), apoptosis (APO, in situ end labelling) and, in part, liver iron and malondialdehyde determination. Apoptosis was similar in all patient subgroups and correlated with hepatitis grading (P = 0.002) and ALT levels (P = 0.004); 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), overall 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, cytoproliferation is more pronounced in chronic HCV-related hepatitis, while APO is not significantly higher than in other types of liver damage, suggesting an imbalance 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.