Does immunosuppression affect the post-transplantation hepatic fibrogenic response?

Funded Activity Summary

Liver transplantation is often the only treatment option for patients who progress to end-stage liver disease after initial treatment has failed. Unfortunately, re-emergence of disease is common and patients often develop fibrosis and cirrhosis (scarring of the liver) in the donor organ. In some cases it has been observed that this scarring often develops rapidly, sometimes in a year or less following transplantation. Re-transplantation is often required. This differs from the usual progression of cirrhosis pre-transplant which often takes years or decades to develop. While essential to prevent rejection of the transplanted organ, immunosuppression is not without side effects. To date, few studies have examined the effect of immunosuppressive agents on the development of hepatic fibrosis and the key fibrosis effector cell type, the hepatic stellate cell. These reports have shown that one of the most commonly used immunosuppressant agents (FK-506) may adversely influence fibrosis progression while rapamycin may prevent fibrosis progression. However little is known regarding the mechanisms through which this occurs. We propose to examine the effect of four different immunosuppressants on fibrosis development both in vitro and in vivo to determine whether scar development or scar breakdown pathways are altered post-immunosuppression. If the factors driving the fibrogenesis in the transplanted organ can be elucidated it may then be possible to develop therapeutic strategies to tackle the problem. This may result in a reduced need for re-transplantation which has obvious benefits to the transplant patient but would also reduce the numbers of donor organs required.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $360,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gastroenterology and Hepatology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Cirrhosis | Hepatic stellate cell | Immunosuppression | Liver | Liver cirrhosis | Liver transplantation

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