Steatosis correlates with hepatic expression of death receptors and activation of nuclear factor-kappaB in chronic hepatitis C.
BACKGROUND
Steatosis is recognized as a predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. The mechanisms that cause increased hepatocellular injury associated with steatosis remain largely unknown.


METHODS
We studied the correlation of hepatic expression of death receptors: Fas and tumour necrosis factor-alpha receptor 1 (TNF-R1), and downstream caspase (caspase-3) with hepatic steatosis by immunohistochemical study in chronic hepatitis C and determined the role of nuclear factor-kappaB (NF-kappaB).


RESULTS
Ninety patients (49 males and 41 females, mean age of 50.5 +/- 10.4 years, genotype 1 or 2) with chronic hepatitis C virus infection were recruited. The factors associated with steatosis grade were body mass index (P=0.004) and fibrosis stage (P=0.034). Moderate/severe steatosis was an independent variable associated with advanced fibrosis stage by stepwise logistic regression analysis. The expression of immunoreactivity for Fas, TNF-R1 and active caspases-3 in liver tissues was significantly correlated with the steatosis grade (P<0.001, P<0.001 and P<0.001 respectively). The extent of active caspases-3 correlated significantly with the expression of Fas (r=0.659, P<0.001) and TNF-R1 (r=0.617, P<0.001). NF-kappaB p65 expression correlated significantly with the extent of Fas (r=0.405, P<0.001), TNF-R1 (r=0.448, P=0.002) and active caspase-3 (r=0.313, P=0.003), and correlated with steatosis grade (P<0.001) but not with inflammatory and fibrosis scores.


CONCLUSIONS
Our observations suggest a mechanism whereby steatosis contributes to the progression of liver injury in chronic hepatitis C through upregulation of death receptors and activation of NF-kappaB.
Hung
Chao-Hung
CH
Department of Internal Medicine, Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. chh4366@yahoo.com.tw
Lee
Chuan-Mo
CM
Kuo
Fang-Ying
FY
Jiang
Shu-Rong
SR
Hu
Tsung-Hui
TH
Chen
Chien-Hung
CH
Wang
Jing-Houng
JH
Lu
Sheng-Nan
SN
Eng
Hock-Liew
HL
Changchien
Chi-Sin
CS
D000328:Adult; D053148:Caspase 3 / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; D053148:Caspase 3