Investigation of the role of the Renin-Angiotensin System in hepatic fibrosis.

Funded Activity Summary

Hepatic fibrosis is a common response to chronic liver injury, during which the normal liver architecture is distorted by scar tissue. Hepatic fibrosis can lead to cirrhosis and liver transplantation may be required for patients with liver failure and hepatocellular carcinoma. The chronic liver injury may result from a number of causes including alcohol, persistent viral infections and metabolic disorders. The mechanisms causing fibrosis in liver are similar to those causing fibrosis in other organs such as kidney and heart. In those organs, the renin-angiotensin system has been shown to contribute to the progression of fibrosis. This system has not been investigated in hepatic fibrosis. We have recently shown in patients with chronic hepatitis C (HCV), that those patients who are genetically pre-disposed to produce higher levels of angiotensin have more liver fibrosis. This application will investigate the role of the renin-angiotensin system in hepatic fibrosis and whether using currently available drugs to inhibit this system can decrease the rate of progression of fibrosis in liver. Liver failure due to chronic HCV infection is currently the leading indication for liver transplantation in Australia. For those patients who fail to respond to anti-viral therapy, there are currently no approved therapeutic options designed to delay or reverse the progression of fibrosis. Based on current known numbers of HCV patients it has been estimated that by the year 2020, over 2000 HCV patients will require a liver transplant each year in Queensland alone. Currently the number of donor livers available allows about 50 transplants per year. Thus there is a desperate need for therapeutic treatments that will delay or reverse the progression of hepatic fibrosis. A successful conclusion to this study will provide a clinically useful treatment strategy that can delay the progression of hepatic fibrosis and thus prevent the need for liver transplantation in many patients.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $246,990.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

angiotensin | hepatic fibrosis | hepatitis C | hepatocellular cancer | liver transplantation | primary biliary cirrhosis

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