Iron metabolism and the cirrhotic liver:studies on iron absorption and hepatic iron kinetics [ 2002 - 2004 ]

Research Grant

Researchers: Prof Darrell Crawford (Principal investigator) ,  Dr Linda Fletcher ,  E/Pr Lawrie Powell ,  Prof Michael Roberts

Brief description Patients with liver disease awaiting liver transplantation often have excess iron in the liver that aggravates the existing liver disease. We have shown that patients with cholestatic liver disease, (due to poor bile excretion), do not have much iron in the liver compared to those patients with hepatocellular cirrhosis, (where the liver cells are damaged). Why this is so is unknown. Iron is normally absorbed from the diet by with the help of special molecules in the small intestine, carried in the blood to the liver where it is used by the cells. We would like to study how the proteins that transport iron in the intestine function and see if this is a different in disease. We would also like to examine exactly which molecules are important in depositing iron in the liver in patients with cirrhosis. We will work on animal models of liver disease as well as humans. We will treat animals so that they have liver disease that resembles human subjects with cirrhosis. These treatments include (1) feeding the animals carbon-tetrachloride, a toxin which damages the liver cells and therefore causes hepatocellular liver injury, and (2) tying the bile duct which stops the flow of bile and this results in cholestatic liver injury. It is known which proteins takes iron into the normal liver cells but no one knows which molecules transport the iron in liver disease. We think they may be different, because when the liver becomes diseased, scarring occurs this results in cirrhosis. Molecules that could easily enter liver cells may now be too big to pass through the openings. These studies are important since they will suggest new treatments to patients with liver disease who are awaiting a liver transplant and the treatment will probably differ depending on which type of liver disease the patient has.

Funding Amount $AUD 256,980.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant