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Liver disease

Liver disease is caused by chronic inflammation and encompasses a wide range of diseases that vary in severity, from mild injury to severe liver fibrosis and scarring or cirrhosis.

These diseases are driven by many factors including viruses, autoimmune processes, genetic diseases, metabolic disorders including diabetes, and toxins such as alcohol.

There are a number of pathways to liver injury, many of which lead to cirrhosis, which is late-stage liver disease. Cirrhosis of the liver is the greatest risk factor for primary liver cancer.

At Centenary our research is looking at the impact of inflammation and potential treatments around a number of areas. These include pathways at the cellular and molecular levels, fatty liver disease in conjunction with diabetes, infections such as hepatitis B, hepatitis C and malaria, and impacts of alcohol use.

Alcohol use

In principle, all alcohol-related liver diseases, including cirrhosis and cancer, are preventable. Liver is the most affected organ by alcohol, metabolising ~98%, increasing the risk of cirrhosis, cancer and significant deaths.

In Australia, ~2% of drinkers/year will develop alcoholic cirrhosis with median survival as low as 1–2 years. Despite public health measures, risky drinking continues to be a major concern worldwide. Alcoholic cirrhosis is predicted to rise as the leading cause of liver disease in Australia and globally. Limited information on genetics and contributing factors makes it difficult for clinicians to predict who amongst the drinkers are at a greater risk of cirrhosis.

This research is unique in Australia, undertaking comprehensive genetics, molecular, animal and clinical approaches, making outstanding advances in identifying clinical risk factors (diabetes, coffee and cannabis use); novel SNPs in lipid biology; developing predictive algorithms for cirrhosis risk in drinkers; and finding drug targets.

Associate Professor Devanshi Seth, Head of the Alcoholic Liver Disease Laboratory leads this research.

Enzyme research

The rise of fatty liver disease and type 2 diabetes is of particular concern. The focus in our research is understanding the roles played by the key DPP4 enzyme family.

We have discovered that the genes for encoding the for enzymes of this family are important drivers of liver cirrhosis. Also, enzymes make excellent drug targets to design. Our liver disease research is focused on certain type 2 diabetes therapies that may also combat fatty liver disease.

This research seeks to understand and develop ways to combat chronic liver diseases and liver cancer.

Professor Mark Gorrell, Head of Liver Enzyme in Metabolism and Inflammation Program leads this research.

Inflammation and fibrosis

This work is devoted to understanding pathways at the cellular and molecular levels that drive liver injury and cancer. These pathways may then be identified as targets to modulate these processes or be used for diagnosis and staging of liver disease and cancer.

We examine the underlying mechanisms that drive primary liver cancer (PLC) looking at liver inflammation, fibrosis and the liver stem cell response.

We use experimental models of cancer and liver injury as well as examine human PLC samples.

Professor Geoff McCaughan, Head of Liver Injury and Cancer Program leads this research.

Immunology

The research is focused on the unique relationship between the liver and the immune system. Our research is helping to improve our understanding of the liver and its impact, wanted and unwanted, on immune responses.

The liver can be detrimental during infections such as hepatitis B, hepatitis C and malaria. These diseases can use the liver as a means of persisting, which can often lead to chronic infection.

We are investigating how the liver induces immune tolerance and how immunity can be enhanced.

Associate Professor Patrick Bertolino and Associate Professor David Bowen, Joint Heads of Liver Immunology Program lead this research.

All four of these Centenary programs and laboratory are tightly linked to the Liver Disease, Liver Cancer and Liver Transplant program at Royal Prince Alfred Hospital.

Impact

In 2015, chronic liver disease was 9th leading cause of deaths in Australia. 1 AIHW

About 1 in 3 Australians has fatty liver. 2 Health Direct

Hepatitis B is a major cause of liver cirrhosis. 3 Hepatitis NSW

Alcoholic liver disease was the most common cause of alcohol-induced death. 4 ABS