title: Caspase activation is associated with spontaneous recovery from acute liver failure.
abstract: Acute liver failure (ALF) has various causes and is characterized by rapid hepatocyte dysfunction with development of encephalopathy in the absence of preexisting liver disease. Whereas most patients require liver transplantation to prevent the high mortality, some patients recover spontaneously and show complete liver regeneration. Because of the low incidence of ALF, however, the molecular mechanisms of liver dysfunction and regeneration are largely unknown. In this study, we investigated the role of apoptosis and caspases in 70 ALF patients using novel biomarkers that allow the detection of caspase activation in serum samples. Compared with healthy individuals, activation of caspases was strongly enhanced in ALF patients. Interestingly, patients with spontaneous recovery from ALF revealed a significantly higher activation of caspases than patients that required transplantation or died, although in the latter patients extensive DNA fragmentation and signs of nonapoptotic cell death were observed. In the spontaneous survivors, increased caspase activation was accompanied by elevated levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (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 caspase-independent cell death might be more relevant in irreversible forms of liver failure. These findings might be important for therapeutic options of ALF but also suggest that measurement of caspase activation might be of prognostic value to predict the outcome of acute liver failure.
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Xandra
authors.initials: X
authors.lastname: Volkmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Anstaett
authors.forename: Johannes
authors.initials: J
authors.lastname: Hadem
authors.forename: Penelope
authors.initials: P
authors.lastname: Stiefel
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Heike
authors.initials: H
authors.lastname: Bantel
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000145:classification / Q000150:complications; D017093:Liver Failure / Q000201:enzymology* / Q000209:etiology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012075:Remission, Spontaneous
chemical_list: D020169:Caspases