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  • Title: [Novel factors playing a role in the pathomechanism of diffuse liver diseases: apoptosis and hepatic stem cells].
    Author: Schaff Z, Nagy P.
    Journal: Orv Hetil; 2004 Aug 29; 145(35):1787-93. PubMed ID: 15493221.
    Abstract:
    Liver diseases can basically be categorised into the forms diffuse and focal. In case of diffuse liver diseases the damages in general affect the whole of the liver, but the alterations are usually present in varying degrees and severity. Relatively stereotypical reactions develop in the liver tissues on the effect of various damaging factors. Some of these reactions and their pathogenic backgrounds are well known, while others have only recently come into focus, like apoptosis and the regeneration-proliferation related hepatic stem cells. The number of damaging effects are naturally much higher than the number of possible response reactions and as a consequence, in many cases the etiological factors can not unambiguously be identified from the tissue alterations. The basic reaction types of the liver can be divided into well defined categories; thus adaptive changes, degeneration and intracellular storage, cell death (necrosis/apoptosis), inflammation, fibrosis and structural reorganisation, as well as regeneration/proliferation. The picture of "classic necrosis" is well known; with the detection of cellular swelling, membrane damage. Apoptosis is characterised by cell shrinkage, nuclear and cytoplasmic disruption, while the cell membrane remains intact. Apoptosis occurs in several liver diseases, with a striking form of appearance being the Councilman-like body seen in viral hepatitis. Apoptosis may have role in the pathogenesis of cholestasis, biliary atresia, the "vanishing bile duct syndrome", and alcoholic liver injury. The regenerative ability of the liver is excellent. The process is influenced by several growth factors and cytokines. In the case of chronic liver damage, however, the regeneration equilibrium becomes upset and irregular. Studies on liver regeneration have led to the recognition of hepatic stem cells. These cells of "oval" morphologic appearance are built up of a primitive structure, making them suitable for this task. Ductular proliferation originating from hepatic stem cells can mostly be recognised in three disease groups: liver regeneration following massive or submassive liver necrosis, ductular proliferation without liver insufficiency, and tumorous liver diseases. At present it is still unclear whether the hepatocyte formation originating from haematopoetic stem cells is a rarely occurring accidental transformation, or rather, under appropriate circumstances, a greatly effective "third" protective system. If the latter is true, this can fundamentally change our view on the pathomechanism of liver diseases, making possible numerous novel therapeutic treatments.
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