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Liver Research Unit

The Liver Research Unit is concerned with studies of the mechanisms of alcohol and iron related liver disease, as well as hepatic fibrosis and anti-fibrotic therapies. This group is led by Professor Darrell Crawford who has an international reputation for his contributions in this field.

Liver disease is a globally significant cause of morbidity and mortality. The prevalence of conditions such as chronic viral hepatitis, alcoholic liver disease, liver disease associated with obesity, hepatocellular cancer and inherited liver iron overload conditions are all increasing at a high rate. Research projects funded by the NHMRC, Queensland Health and private industry are seeking to address key issues in understanding the factors involved in the progression of liver disease as well as novel therapies to retard the progression of liver disease and to treat chronic viral hepatitis. Important collaborations have been established with Liver Transplant Program, PA Hospital and the Department of Gastroenterology and Hepatology, PA Hospital.

In addition to basic research studies, this research program recognizes its important role in fostering the academic development of early career clinicians. To that end, a fellowship in liver disease has been created whereby a significant component of time in that position is ’protected‘ for clinical research.

Furthermore a clinical trial program in liver disease has been established with active participation in phase II and III clinical trials of antiviral agents for chronic viral hepatitis. This program is supported by a clinical trial co-ordinator with ten years experience, as well as other appropriate infrastructure requirements for clinical trials.

The ultimate end point of nearly all liver insults is hepatic fibrosis and cirrhosis (i.e. liver scarring). Despite recent advances in antiviral therapy, the majority of liver diseases are relentlessly progressive. Therefore, targeting the fibrogenic process to delay disease progression would likely reduce morbidity and mortality from liver disease.  GMRC researchers lead by Prof Crawford will investigate the potential anti-fibrotic role of a medication currently used as an immunosuppressive agent. Experiments have been conducted exposing hepatic stellate cells (i.e. the cells that produce scarring in cirrosis) to varying concentrations of this agent and results have shown profound anti-fibrotic effect even at very low drug concentrations. These studies have been extended into animal models of liver disease and it has been found that administration of these agents dramatically reduces hepatic collagen production. This project is concerned with extending that research in order to examine other models of liver diseases and variable dosing regimes with the ultimate aim of conducting a large clinical trial involving human subjects with liver disease.

In addition, the liver research project will have a continued focus on the interaction between alcohol and iron and the role that both of these agents play in the progression of alcoholic liver disease. This is also a leading edge series of studies that have shown that alcohol directly, and indirectly, influences proteins involved in iron metabolism ultimately resulting in an increased hepatic iron concentration which perpetuates and exacerbates the underlying alcoholic liver injury. It is of significant relevance that a number of oral iron chelators have recently been developed or licensed and the role of these agents in humans with alcoholic liver disease warrants further study.