Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis.
OBJECTIVE
Although human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease, its clinical and biological significance has not been investigated in alcoholic hepatitis (AH). The aim of this study was to quantify hepatocyte apoptosis in AH and to attempt to relate it to the clinical and biological severity of the disease.


METHODS
The hepatocyte apoptotic index was determined using a double in situ transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labelling on 35 liver biopsies from patients with AH lesions of different severities. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining.


RESULTS
The hepatocyte apoptotic index ranged from 0.3 to 28% and was related to the severity of alcoholic hepatitis as measured by the Maddrey score (P < 0.05; Mann-Whitney test) while ballooning (which reflects hepatocytes potentially undergoing necrosis) and neutrophil indexes were not.


CONCLUSIONS
This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. Co-localization of apoptotic hepatocytes with neutrophils and the strong quantitative correlation would suggest an apoptosis dependent transmigration of neutrophils.
Department of Pathology, H pital Jean Verdier, Bondy, France. marianne.ziol@jvr.ap-hop-paris.fr
M
M
Ziol
M
M
Tepper
M
M
Lohez
G
G
Arcangeli
N
N
Ganne
C
C
Christidis
J C
JC
Trinchet
M
M
Beaugrand
J G
JG
Guillet
C
C
Guettier
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D053938:DNA Fragmentation; D005260:Female; D006519:Hepatitis, Alcoholic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism
D000199:Actins; D016256:Lewis X Antigen; D010446:Peptide Fragments