Intrahepatic activation of caspases in human fulminant hepatic failure.
OBJECTIVE
Apoptosis has been implicated in the pathogenesis of fulminant hepatic failure (FHF) potentially involving caspases. Thus far, apoptosis in FHF has mainly been studied in animal models while human data are sparse.


METHODS
Caspases-3, -8 and -9 activities and Fas expression were analyzed in correlation to TdT-mediated dUTP nick end labelling (TUNEL) positive apoptotic cells in livers of patients with FHF (n=26), chronic liver disease (CLD) (n=60) and normal controls (NC) (n=10).


RESULTS
Numbers of TUNEL-positive cells were higher in FHF than in CLD and NC (P<0.001) correlating to the intrahepatic activities of caspase-3. The highest caspase-3 activities were found in fulminant hepatitis B, significantly surpassing those in FHF of any other etiology. In fulminant hepatitis B, caspase-9 activity was also higher than in controls, while caspase-8 activation was not higher than in NC. Unlike caspase-3, caspases -8 and -9 activities were not correlated to the numbers of TUNEL positive cells. Fas expression was also the highest in FHF but did not differ between hepatitis B virus-FHF and other FHF.


CONCLUSIONS
Our data indicate differential activation of intrahepatic caspases in FHF depending on the underlying etiology. Massive activation of caspases in fulminant hepatitis B confirms a pivotal role of apoptotic pathways in the pathogenesis of human fulminant hepatitis B.
Leifeld
Ludger
L
Department of Internal Medicine I, University of Bonn, Germany. ludger.leifeld@ukb.uni-bonn.de
Nattermann
Jacob
J
Fielenbach
Magdalene
M
Schmitz
Volker
V
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D000328:Adult; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000201:enzymology; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000201:enzymology; D017114:Liver Failure, Acute / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged
D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9