Risk and recovery of outflow obstruction in living-related liver transplantation: The influence of liver perfusion on regeneration and outcome

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Perfusion-related problems account for numerous complications after liver transplantation. Outflow obstruction represents one of the key surgical problems in adult living-related liver donation, as the donor liver has to be split into two hemi-livers and middle hepatic vein branches have to be transected. Insufficient drainage compromising liver function and leading to an impaired regeneration of the dependent territories is the consequence, increasing the risk for the patient by additional reduction of functional liver mass. Reduction of functional liver mass and impaired regeneration were prevented experimentally in rat model of extended liver resection by applying a vessel-oriented parenchyma preserving resection technique instead of the formerly used mass ligation technique. Recovery of the impaired drainage of outflow obstructed areas by vascularization of dilated sinusoids in combination with a remodeled liver architecture and an impaired regeneration was observed in a newly developed surgical model. These and other clinical and experimental observations lead to the hypothesis that focal outflow obstruction is the key event compromising the functional capacity and the regeneration of the dependent territories, suggesting a local regulation of liver regeneration. The first aim of this interdisciplinary project is the evaluation of the functional relevance of outflow obstruction in terms of liver function, regeneration, and revascularization employing the rat and woodchuck model. The second aim is to investigate the underlying mechanism and its pharmacological modulation. The third aim is to assess the biological importance of outflow obstruction not only in the model of liver resection but also after partial liver transplantation. Based on serial histological sections, software algorithms for automatic analysis and three-dimensional visualization of morphological data will be developed. This will lead to a deeper understanding of the regulatory influence of focally impaired liver perfusion not only on liver regeneration in terms of volume and vascular regeneration, but also in terms of the spatial distribution of molecular processes during the course of liver regeneration.