Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: The role of etiology, disease activity, iron, and lipid peroxidation

✍ Scribed by F Farinati; R Cardin; A D'Errico; N De Maria; R Naccarato; A Cecchetto; W Grigioni

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 848 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230625

✦ Synopsis

Hepatitis B virus (HBV)-and hepatitis C virus (HCV)-

The pathophysiology of liver damage mediated by related liver damage is linked to an increased risk of hepatitis B virus (HBV) and the mechanisms underlyhepatocellular carcinoma, but the mechanisms underlying its oncogenic activity have been thoroughly investiing hepatitis C viral activity are not known. We therefore gated in the last 20 years. As for the former, it has compared hepatocellular proliferative activity in become clear that a cell-mediated immune response to chronic C virus-related hepatitis and in liver damage HBV gene products on the cellular membrane of hepaof other etiology. Hepatocyte proliferation rate was intocytes is the major cause of liver injury. 1 Concerning vestigated in 56 patients with chronic hepatitis using the latter, in addition to the obvious role played by the the Ki67 MIB1 monoclonal antibody in archival material.

process of necrosis and regeneration typical of cirrho-

According to etiology, the patients were subgrouped as sis, the results of various studies point to different follows: HCV (34), HBV (11), Alcohol (4), HCV / Alcohol (4), and Hemochromatosis (3). Proliferation rate was cor-hypotheses: (1) insertional mutagenesis with the modirelated with age, sex, etiology, disease activity, liver iron fication of either sequences coding for oncogenes or stestorage, free-radical production, and glutathione levels roid receptors, 2 or cyclin A gene 3 ; or (2) transactivation, by regression and discriminant analysis. HCV-positive through HBV X gene protein or pre-S/S protein, deleted patients had significantly more MIB1-positive hepatoat the C-terminal, altering host gene expression, and cytes in the periportal area (P õ .011) and in the lowthus ultimately leading to malignant transformation proliferating perivenular area (zones 2 and 3) (P õ .05). of the hepatocyte. [4][5][6][7] The number of MIB1-positive cells correlated directly Much less is known about the mechanisms of liver with alanine transaminase (ALT) levels, Knodell index damage and oncogenesis related to hepatitis C virus (KI), and, inversely, with iron saturation. By stepwise (HCV). Whether HCV is directly cytopathic or the damdiscriminant analysis, ALT levels and etiology were identified as single independent variables. These data age is immunologically mediated, as in HBV infection, suggest that HCV infection induces increased and abis still open to debate. 8 While humoral and cellular normal hepatocyte proliferation, which might be related responses appear to be important, 9 the particular histoto the increased risk of hepatocellular carcinoma in palogical features, such as the almost invariable presence tients with HCV-related liver damage. (HEPATOLOGY of steatosis 10 suggest a direct cytopathic effect. Clinical 1996;23:1468-1475.) evidence has also pointed to the role of iron accumulation in HCV-mediated liver damage, 11 and we have documented an increased liver iron storage, lipid peroxidation, and reduced glutathione (GSH) turnover Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; GSH, re-activation in patients with chronic HCV-related liver duced glutathione; TSI, transferrin saturation index; KI, Knodell index; GSSG, disease. 12 With respect to the mechanisms underlying oxidized glutathione; MDA, malondialdehyde; ALT, alanine transaminase.