Multifactorial effect of hepatocyte growth factor (HGF) on the microscopic regeneration of liver allograft in recipients who underwent transplantation from living donors
B. Handan Ozdemir1, Gonca Ozgun1, Aysegul Yucel Polat1, Mehmet A. Haberal2.
1Pathology, Baskent University, Ankara, Turkey; 2Transplantation, Baskent University, Ankara, Turkey
Introduction: Although partial liver allografts from living donors have near-complete regeneration of their liver volumes within weeks after transplantation, the microscopic range of regeneration is not well known. HGF plays critical roles in the regeneration process of various tissues by stimulating the proliferation, vascularisation, and migration of progenitor cells. HGF exerts protective effects on organs via anti-apoptotic and anti-inflammatory signals. Our aim is two folds; first, to evaluate the protective and regenerative effect of HGF on partial liver allografts, second, to analyze the prognostic impact of HGF on long-term allograft survival.
Methods: Biopsies of 62 patients scored for inflammation and fibrosis. Angiogenesis highlighted with CD31, hepatocyte proliferation studied with Ki-67, and apoptosis evaluated with the TUNNEL method. Hepatic expression of HGF, 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: HGF showed a positive correlation with angiogenesis (p<0.001) and an inverse relationship with apoptosis, inflammation, and macrophage infiltration (p<0.001). The proliferation index of hepatocytes increased with increasing HGF expression (p<0.001). TGF-β and TNF-α showed an inverse correlation with the intensity of HGF expression (p<0.001). Acute rejection episodes increased with decreasing HGF expression (p=0.001). The degree of inflammation showed correlation with apoptosis, TGF-β and TNF-α (p<0.01). The development of LF showed a significant correlation with the degree of apoptosis, inflammation, TGF-β, and TNF-α expression (P<0.01). The development of LF decreased with increasing expression of HGF (p<0.001).The mean graft survival was 39±6, 64±9, and 113±7 months for patients with negative, focal, and diffuse HGF expression, respectively (p<0.001).
Conclusion: HGF is critical for organo-protection and liver regeneration in recipients with partial liver allografts. We suggest that HGF-based drugs show promise as part of a new arsenal in the fight to suppress allograft failure due to incomplete liver regeneration.
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