Development of method and instrument for quantitative assessment of liver steatosis – STEAQUANT

Liver transplantation (LT) is the only available treatment for patients with fulminant hepatitis or end-stage intractable liver failure and the best treatment for cirrhotic patients with HCC. The main concern in liver transplantation is the graft shortage leading to the use of marginal livers. The most important criteria of graft quality is the degree of steatosis which is a major cause of primary liver graft dysfunction and also a source of long term poorer evolution of the graft. Hitherto, the quality control of the grafts relies upon histological examination of frozen sections to assess the degree of steatosis. However, this is nor a quantitative neither a precise method given the poor inter-observer reproducibility. The incapacity of usual histological methods to rigorously provide an objective assessment of steatosis and the major importance of graft steatosis in liver transplantation outcome justify the absolute need of a new method for precise quantitative assessment of steatosis in liver grafts prior to transplantation.
The goal of the proposal is the development of an instrument with a method based on infrared (IR) microspectroscopy for rapid and precise assessment of liver graft quality and its establishment to the hospital. We have already demonstrated that IR measurement on frozen tissue sections from biopsies is closely related to its lipid content. A prototype instrument will be developed for rapid acquisition of infrared spectra on tissue sections. The instrument will be equipped with a thermal source, an interferometer and a sensitive detector. This instrument will allow very fast raster scanning over large areas of a tissue section. A method for quantitative assessment of steatosis on frozen tissue sections from biopsies of graft by using IR microspectroscopy will be set up. The method will allow determining the lipid content by measuring the intensity and the calculated areas of selected peaks in infrared spectra obtained from a large area on a tissue section. This method will be adapted to optimal use of the instrument developed above. The correlation established between the lipid content and the graft quality will allow providing a statement on graft quality based on infrared spectra. A specific software will be developed for easy use and data interpretation. The method will be rapid, sensitive, robust, easy to use, not expensive and quantitative. The instrument and the method developed will be further installed at Paul Brousse Hospital into the Department of Pathology for routine use in graft quality control. Such equipment should be implemented in any hospital performing liver transplantation.