TY - JOUR
T1 - Apoptotic mechanisms in fulminant hepatic failure
T2 - Potential therapeutic target
AU - Singhal, Shashideep
AU - Jain, Shilpa
AU - Kohaar, Indu
AU - Singla, Montish
AU - Gondal, Ranjana
AU - Kar, Premashis
PY - 2009/7
Y1 - 2009/7
N2 - INTRODUCTION: Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. METHODS: Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. RESULTS: Immunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH. CONCLUSIONS: Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.
AB - INTRODUCTION: Pathogenesis of fulminant hepatic failure (FHF) in nonacetaminophen etiology is not elucidated. We have investigated the significance of tumor necrosis factor (TNF) type-I receptor (TNF-R1) and Fas receptor (CD95, APO-1) in FHF. METHODS: Liver biopsy samples were obtained from 14 FHF patients. Liver tissue samples of 10 patients with acute viral hepatitis (AVH) and 10 cases who died, unrelated to liver disease served as tissue biopsy controls. Immunohistochemical methods were employed to analyze expression of TNF-R1 and Fas expression in hepatocytes. RESULTS: Immunohistochemical analysis revealed high expression (P<0.001) of Fas and TNF-R1 in FHF cases in relation to AVH cases. This expression was more in cytoplasm of apoptotic hepatocytes than viable swollen hepatocytes and this correlated with the extent of hepatocyte apoptosis. The mean apoptotic index was significantly (P<0.001) higher in FHF in relation to AVH. CONCLUSIONS: Enhanced expression of TNF-R1 and Fas receptors on the apoptotic hepatocytes suggest that both may be involved in the pathogenesis of FHF and seem to be potential therapeutic target.
KW - Apoptosis
KW - Fas
KW - Fulminant hepatic failure
KW - TNF-R1
UR - http://www.scopus.com/inward/record.url?scp=68149165909&partnerID=8YFLogxK
U2 - 10.1097/PAI.0b013e3181906f6d
DO - 10.1097/PAI.0b013e3181906f6d
M3 - Article
C2 - 19077906
AN - SCOPUS:68149165909
SN - 1541-2016
VL - 17
SP - 282
EP - 285
JO - Applied Immunohistochemistry and Molecular Morphology
JF - Applied Immunohistochemistry and Molecular Morphology
IS - 4
ER -