Sinusoidal Cell Function Research Articles

Sinusoidal communication in chronic liver disease.

The liver sinusoid, mainly composed of liver sinusoidal endothelial cells, hepatic macrophages and hepatic stellate cells, shapes the hepatic vasculature and is key maintaining liver homeostasis and function. During chronic liver disease (CLD), the function of sinusoidal cells is impaired, being directly involved in the progression of liver fibrosis, cirrhosis, and main clinical complications including portal hypertension and hepatocellular carcinoma. In addition to their roles in liver diseases pathobiology, sinusoidal cells' paracrine communication or cross-talk is being studied as a mechanism of disease but also as a remarkable target for treatment. The aim of this review is to gather current knowledge of intercellular signalling in the hepatic sinusoid during the progression of liver disease. We summarise studies developed in pre-clinical models of CLD, specially emphasizing those pathways characterized in human-based clinically relevant models. Finally, we describe pharmacological treatments targeting sinusoidal communication as promising options to treat CLD and its clinical complications.

Potentiation of Adverse Effects of Cold by Warm Ischemia in Circulatory Death Donors for Porcine Liver Transplantation

BackgroundWider use of donors after circulatory death (DCD) could reduce mortality on the liver transplantation waiting list. We previously reported that pig livers exposed to ≥30 minutes of warm ischemia followed by 4 hours of cold ischemia are at high risk of primary graft nonfunction. We sought to determine how prolonged cold ischemia, after a short, normally well-tolerated period of warm ischemia affects graft function and recipient survival using a porcine model of liver transplantation. Materials and MethodsLivers were transplanted after exposure to no warm plus 4 hours cold ischemia (group 1); 15 minutes of warm and 4 hours of cold ischemia (group 2); no warm and 8 hours of cold ischemia (group 3); or 15 minutes of warm and 8 hours of cold ischemia (group 4). Recipient survival, graft dysfunction incidence, liver function (prothrombin time), hepatocellular damage (aspartate aminotransferase), sinusoidal cell function (hyaluronic acid), and inflammation (tumor necrosis factor-α) were recorded after transplantation. Biopsies were scored for ischemia–reperfusion injury. ResultsDay 4 survival in group 4 was 0% versus 100%, 83%, and 100% in groups 1, 2, and 3, respectively. Recipients in group 4 exposed to short warm but prolonged cold ischemia displayed severe graft dysfunction, the highest peak transaminase, the greatest inflammatory response, more sinusoidal endothelial cell dysfunction and, the worst histologic score for ischemia–reperfusion injury. ConclusionsLiver grafts from DCD donors, even when exposed to short periods of warm ischemia, did not tolerate prolonged cold ischemia well and should be transplanted without delay.

Effect of calcium antagonists on rat liver during extended cold preservation-reperfusion.

Nisoldipine, a calcium antagonist, has been reported to improve the quality of grafted rat livers. We thus assessed the protective effect of two calcium antagonists, nisoldipine and nickel, during extended cold ischemia-reperfusion. Rat livers were isolated and perfused before or after 24 hr of cold ischemia in University of Wisconsin solution (4 degrees C) with or without nisoldipine or nickel. Sinusoidal endothelial cell and hepatocyte functions were measured by hyaluronic acid and taurocholate elimination, respectively. Similar alterations in hepatocyte and sinusoidal cell functions were found in all groups after cold ischemia with or without calcium antagonists. In a second set of experiments, liver transplantation was performed in two groups of rats with livers stored under identical conditions with or without nisoldipine. Seven of 12 animals (62.5%) in both groups survived for over 10 days after 24-hr preservation in University of Wisconsin solution. Survival rates were similar in both groups. Calcium antagonists do not appear to have a direct protective effect on sinusoidal endothelial cell and hepatocyte functions, nor on the overall liver preservation after extended cold preservation-reperfusion.

Oxford Textbook of Clinical Hepatology

This new monograph was written largely by outstanding European investigators to contain all that is needed by the clinician treating liver disease. It is organized by 31 broad topics covering anatomy, pathology, pathogenesis, testing, clinical syndromes, and specific categories of disease and treatment. Special problems of systemic disease affecting the liver, effects of the liver on other organs, liver disease in the young or very old, and surgery are additional important topics. Each section is divided into one to 28 complete monographs on the particular topic at hand. The chapters feature boldface headings, line drawings, tables, and, occasionally, photomicrographs to present all information relevant to that topic. Several chapters are superbly illustrated with line drawings correlated with ultrasound and computed tomographic images, photomicrographs, or electron micrographs. Liver and portal vein anatomy, histology, function of sinusoidal cells, and structure of hepatic viruses are model chapters communicating clearly their message through combination