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P-2.107 Increased level of serum cholesterol and apoptosis together induces the development of liver fibrosis and early allograft loss

Binnaz Handan Ozdemir, Turkey

Prof. Dr
Pathology
Baskent University

Abstract

Increased level of serum cholesterol and apoptosis together induces the development of liver fibrosis and early allograft loss

B. Handan Ozdemir1, Gonca Ozgun1, Ebru H. Ayvazoglu Soy2, Nihan Haberal1, Mehmet A. Haberal2.

1Pathology, Baskent University, Ankara, Turkey; 2Transplantation, Baskent University, Ankara, Turkey

Background: Hypercholesterolemia (HC) induced oxidative stress known to facilitate apoptosis, steatosis, and TGF-β induced liver injury. Apoptosis, in turn, can trigger inflammation, and fibrosis. Apoptotic hepatocytes can act as a mediator of hepatic stellate cell (HSC) activation, and the engulfment of apoptotic bodies by HSCs stimulates fibrogenic activity. We evaluate the influence of  HC on the development of liver fibrosis (LF) and long-term graft survival.
Methods: Biopsies of 70 patients scored for inflammation, steatosis, and fibrosis. Activated HSCs determined by the expression of α-SMA and the apoptosis highlighted with the TUNNEL method. Hepatic expression of TNF-α and TGF-β evaluated by immunohistochemistry. Follow-up biopsies analyzed for the development of LF during 18 months after biopsy.
Results: HSC activation and steatosis found higher in recipients with HC (p<0.001). The mean cholesterol levels were 184±12 and 80±9,4 mg/dl for cases with and without HSC activation, respectively. Apoptosis found higher in cases with HSC activation (24±2) compared to cases without HSC activation (9,5±1,3) (p<0.001). TGF-β and TNF-α expression found to increase with an increasing level of cholesterol (p<0.001). Both TGF-β and TNF-α expression showed positive correlation with HSC activation and the degree of apoptosis. Acute rejection episodes found higher in cases with HC (p<0.01). The degree of inflammation showed correlation with HSC activation, apoptosis, TGF-β, and TNF-α expression (p<0.01). The development of LF showed a significant correlation with the degree of mean cholesterol level, HSC activation, TGF-β, and TNF-α expression (P<0.001). The mean graft survival was 87,5±8,6 and 115±3,3 months for patients with and without HC, respectively (p=0.01).
Conclusion: High cholesterol induces apoptosis, and in turn, both of them together triggers the activation of HSCs, expression of TGF- β, and TNF-α. Hence, TGF-β and TNF-α signals appeared to accelerate the HC induced hepatic inflammation, fibrosis, and oxidative stress facilitating liver disease progression.

Presentations by Binnaz Handan Ozdemir

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