ABSTRACT
Th e majority of alcohol metabolism occurs in the liver and as a consequence excessive and prolonged exposure to alcohol can result in alcoholic liver disease (ALD). Th e three stages in the pathology of ALD-steatosis, hepatitis and fi brosis-are histologically distinct facets of pathology, but it is likely that some overlap as each stage occurs. Recent interest has focussed on the more injurious hepatitis/fi brosis stage, but with emerging pathology, non-alcoholic fatty liver disease, alterations occurring at the steatosis stage suggest that every stage has a very important role to play. From this, it is unclear whether biochemical alterations arising at each stage are independent or perhaps dependent on various conditions/ stimuli involved in subsequent stages. In the UK, the number of patients admitted for acute alcoholic hepatitis and alcoholic liver disease (ALD) have been rapidly increasing, and this has also coincided with high mortality rates. Clearly a better understanding of the factors and pathways involved will ultimately lead to improved patient treatment. Th is chapter therefore describes some of the major pathways of cell death involved in ALD and seeks to address some of the recent issues surrounding the biochemical
and metabolic regulations of these pathways caused by alcohol exposure. While necrotic cell damage is involved throughout the disease process, the extent to which mitochondrial apoptosis contributes is less clear. Factors thought to be largely involved in apoptotic cell death include ATP regulation, oxidative stress and cytochrome c release. Finally, how mitochondrial intervention strategies could be putatively employed as a future treatment will be discussed.
