The Impact of Liver Transplantation on Reticuloendothelial Clearance Capacity

Introduction

Liver cells called hepatocytes undertake the most important metabolic functions of the liver. The liver also contains a large number of immune cells called Kupffer cells. These cells act as a filter removing bacteria and other dangerous substances from the blood passing through the liver. Although we know and understand a great deal about how liver cells behave and function after transplant we have no idea what happens to the immune cells in the liver. These immune cells make up 85% of the total body reserves of these cells and serve an important function by clearing bacteria and bacterial products from the blood. A failure of these cells is associated with risk of infection. Infections, blood clotting disorders and many other serious medical issues are typical for patients suffering from chronic liver failure.

This study will use microscopic particles of a human protein called albumin in the form of microspheres to simulate bacteria in the blood. We can detect these microspheres by attaching a radioactive label to the spheres and measuring emission in a detector called a gamma counter. The level of radiation is quite small and similar to a bone scan. We have previously shown that healthy liver rapidly clears these albumin microspheres from the blood. We have also shown previously that after major liver surgery there is a delay in clearance of microspheres, which we believe equates to a poorly functioning innate immune system.

Liver transplantation is the only successful life-extending treatment for patients with chronic liver failure and cirrhosis. During liver transplantation it is known that a proportion of hepatocytes damaged and recover following the transplant. We want to establish the immediate particulate clearance capacity of the liver following transplantation and the pattern of recovery one week later. This is used as a surrogate for liver clearance of bacteria and bacterial products.

We also intend to measure the production of a set of proteins called acute phase proteins, which are produced by the liver and may be important in helping immune cells recognize bacteria. These proteins, also called opsonins, bind to the walls of bacteria and make it easier for immune cells to attach to the bacteria and eat them.