This study details a novel therapeutic strategy for bilirubin elimination from the blood of animal models. This therapy may help improve the prognosis of patients with jaundice.
There are several theoretical pathophysiological approaches to filter serum bilirubin in cases of liver failure. One approach would be to increase liver regeneration or perform liver transplantation. Unfortunately, the current supply of acceptable donor livers is not adequate to meet the high demands of listed patients awaiting transplantation, resulting in thousands of deaths each year. An extracorporeal system is another promising feasible approach to liver support. However, evidence suggests that the sole use of liver support systems to remove bilirubin is not adequate to improve survival in patients with liver failure[7, 11–13] because these systems can only partially replace the physiological function of the liver.
In this study, we proposed a novel therapy to eliminate bilirubin from serum. A liver preserved in vitro was perfused with the blood of a jaundiced rat through cross-circulation. As the carotid artery pressure is higher than that of the jugular and portal veins, studies suggested that if the liver was perfused with the blood at a higher pressure, it might disturb the microcirculation and increase the rate of hepatocellular apoptosis[14–16]. However, no obvious hepatocyte apoptosis was detected on histological examination of the liver in vitro after treatment. This might have been because the pressure of the arterial blood significantly decreased after passing through the catheter. In addition, the liver was well perfused during the treatment and was able to produce bile, indicating that the liver can play a role in detoxification and secretion in vitro.
Cross-circulation between two humans has been found to be effective for treating uraemia, treatment of liver failure, provision of large numbers of leukocytes, and cardiopulmonary bypass during cardiac surgery[17–21]. However, it appears that chance selection of a donor and recipient of divergent histocompatibility might result in severe and even potentially fatal outcomes, such as immunologic complications, disease transmission, and compromised donor safety. In this study, cross-circulation was developed between the organ preserved in vitro and the recipient, which might have helped avoid the above problems. In addition to a significant decrease in serum bilirubin, our method also helped reduce 48h survival of the jaundiced rats. Unlike other therapies for removing bilirubin from serum, this therapy could compensate for all liver functions; this might be the main reason for improved 48h prognosis in model rats.
Although the results of this study are encouraging, several limitations should also be considered. First, this study only proved that this novel treatment could reduce the serum bilirubin level of an individual with hyperbilirubinemia and improve the long-term survival in an animal model. The effect of this treatment on coagulation function and other toxic substances in serum remains unclear. In addition, this study only verified the feasibility and effectiveness of the novel treatment method in the rat; thus, further exploration is needed in larger mammals.