0515. Watch this 'spase'

Understanding of apoptosis or controlled cell death is a relatively recent addition to medical knowledge and even more recent is the recognition that a pathological process such as hepatitis C (HCV) infection might activate the apoptotic cascade. Hepatologists have long known that monitoring of alanine aminotransferase (AAT) is useful in the identification of those HCV-infected patients who have severe liver damage and are candidates for treatment with ribavirin and interferon. These subjects are considered to predominantly have uncontrolled, inflammatory cell death. However they have also known that up to 30% of patients with chronic HCV infection have normal AAT levels but liver biopsy is positive for cell damage. Recent research has found that in this sub-group of patients there appears to be mainly controlled, non-inflammatory cell death. Whereas AAT is useful in the former group, other products are detectable in the latter. Apoptosis involves intracellular activation of a series of caspases which are enzymes that propagate a signaling cascade leading to controlled cell death. Activated caspases cleave intracellular proteins, some of which are cell-type specific. In the liver cytokeratin 18 is cleaved and a detectable fragment is released into the circulation. These fragments are detectable in 'AAT-positive' HCV infections but are also present in the 'AAT-negative liver damage-positive' sub-group, with a positive correlation between fragment level and degree of damage. This marker of controlled cell death opens the door for other studies involving other tissues, organs and cleavage products in situations in which currently-available markers of cell damage don't correlate with histological evidence of an underlying ongoing process.

Read more:
Lancet 2005; 365:1293-4
Hepatology 2004; 40: 1078-87
Gastroenterology 1996; 110: 1238-43
Gastroenterology 2004; 127: 1724-32