Abstract
novel biomarkers that allow the detection of caspase activation and the discrimination between apoptotic and necrotic cell death in serum samples. Methods: Caspase activity and apoptosis (TUNEL) were investigated in liver tissue. As markers of liver regeneration TNF-alpha and IL-6 (ELISA) were detected in serum. Caspase-cleaved and total CK-18 (ELISA) was measured to discriminate between apoptotic and necrotic cell death. Results: Compared to healthy individuals, activation of caspases was strongly enhanced in ALF patients. Interestingly, patients with spontaneous recovery from ALF (n = 24) revealed a significantly higher activation of caspases than patients that required transplantation or died (n = 46), although in the latter patients extensive DNA fragmentation and signs of non-apoptotic cell death, i.e. elevated total CK-18 levels, were observed. In the spontaneous survivors, increased caspase activation was accompanied by elevated levels of TNF-alpha and IL-6, important cytokines involved in liver regeneration. Conclusions: Our data suggest that caspase activation and apoptosis are involved in ALF of patients with spontaneous recovery, whereas caspaseindependent cell death appears to be more relevant in irreversible liver failure. These findings might be important for the development of new therapeutic strategies in ALF.
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