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Hepatocyte Growth Factor (HGF) Prevents the Apoptotic and Anti-Angiogenic Effect of Hypercholesterolemia on Hepatocytes in Liver Allografts

H. B. Ozdemir1, G. Ozgun1, A. Yucel Polat1, N. Haberal1, G. Moray2, M. Haberal2

1Pathology, Baskent University, Ankara, Turkey, 2Department of General Surgery, Division of Transplantation, Baskent University, Ankara, Turkey

Meeting: 2020 American Transplant Congress

Abstract number: A-300

Keywords: Growth factors, Hepatocytes, Outcome

Session Information

Session Name: Poster Session A: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Background: Hypercholesterolemia (HC) impairs angiogenesis and induces apoptosis in livers. This hyperlipidemic impairment of angiogenesis reported associated with reduced bFGF. HGF stimulates proliferation, angiogenesis, and plays a critical role in the regeneration process of the liver. HGF also acted as a metabolic regulator and increases in patients with hyperlipidemia. We evaluate whether HGF has a protective effect on hepatocytes of recipients with HC.

*Methods: Methods: Biopsies of 68 patients scored for steatosis, fibrosis, and inflammation. Angiogenesis highlighted with CD31 and apoptosis evaluated with the TUNNEL method. Expression of HGF, bFGF, TNF-α, and TGF-β evaluated by immunohistochemistry. Follow-up biopsies analyzed for the development of LF during 18 months after the initial biopsy.

*Results: Results: The degree of angiogenesis and bFGF decreases while the degree of apoptosis and macrophage increases with increasing level of cholesterol and triglycerides (p<0.001). Liver TGF-β and TNF-α expression found to increase with increasing serum cholesterol and triglycerides (p<0.01). The development of LF showed a significant correlation with the degree of mean cholesterol level, TGF-β, and TNF-α expression (P<0.001). HGF shows a significant correlation with the degree of angiogenesis and inverse correlation with apoptosis, macrophage infiltration, TGF-β, and TNF-α expression (p<0.001). The development of LF decreases with increasing expression of HGF (p<0.001). Of 30 patients with HC, 15 showed HGF expression (Group1) while remaining did not (Group2). The degree of angiogenesis found higher in Group1 than Group 2 (p<0.001).Group1 showed lower degree of apoptosis, TGF-β, TNF-α, and lower incidence of LF than Group2 (p<0.001). Mean graft survival was 39±6,3, 62±8,2, and 116±7 months for patients with negative, focal, and diffuse HGF expression, respectively (p<0.001).

*Conclusions: Conclusion: HGF is critical for organo-protection and liver regeneration under pathophysiological conditions. We suggest that HGF-based drugs show promise as part of a new arsenal in the fight to suppress allograft failure.

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To cite this abstract in AMA style:

Ozdemir HB, Ozgun G, Polat AYucel, Haberal N, Moray G, Haberal M. Hepatocyte Growth Factor (HGF) Prevents the Apoptotic and Anti-Angiogenic Effect of Hypercholesterolemia on Hepatocytes in Liver Allografts [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/hepatocyte-growth-factor-hgf-prevents-the-apoptotic-and-anti-angiogenic-effect-of-hypercholesterolemia-on-hepatocytes-in-liver-allografts/. Accessed May 28, 2025.

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