Why do some heavy drinkers get liver cirrhosis and some don't?
The US government is investing $2.5 million in a Sydney-based study to determine the role of genetics in alcoholic liver disease. It should lead to better diagnosis and treatment of the condition - a silent epidemic that costs $3.8 billion a year in Australia alone.
The study is conceived and led by Dr Devanshi Seth, from the Royal Prince Alfred (RPA) Hospital's Drug Health Services and the Centenary Institute, University of Sydney.
"We still do not understand why only a proportion of moderate to heavy drinkers get liver cirrhosis," said Dr Seth.
"Nothing so far has been able to explain the unpredictability of why some people get cirrhosis and others who drink equal amounts don't."
We hope that by analysing the genes ... we can detect the genetic risks that predispose some drinkers to get alcoholic liver cirrhosis.
Dr Seth and her colleagues will soon start testing the genes of hundreds of Sydneysiders and thousands of others in six countries with the support of the grant from the US National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health.
"Apart from alcohol consumption, several contributory factors, including diet, lifestyle, mental health, viral infection and gender, influence the risk of developing cirrhosis," Dr Seth said.
There is evidence that genes influence the development and progression of this disease.
"We hope that by analysing the genes in a large international group comprising thousands of drinkers we can detect the genetic risks that predispose some drinkers to get alcoholic liver cirrhosis."
Like other multi-factorial diseases, alcoholic liver cirrhosis is controlled by a number of genes, each of which makes a small overall contribution. Previous genetic searches have been inconclusive because the studies performed to date have generally been too small to yield definitive results.
"The lack of specific markers for diagnosis and effective treatment compound the burden of the disease. That is why this research is so important," says Dr Seth. "The results will help us identify and treat the people most at risk from drinking."
While the disease has been predominantly seen among men over 50 years of age, it is becoming more frequent worldwide among younger adults including women.
... (alcohol) contributes to 50 percent of the total burden of liver disease and to 15 percent of liver transplants.
"This study is an important addition to Centenary's liver research effort," says Professor Mathew Vadas, Executive Director of the Centenary Institute, University of Sydney.
"Alcoholic liver disease is the leading cause of alcohol related death and contributes to 50 percent of the total burden of liver disease and to 15 percent of liver transplants," he says.
Dr Seth formed the GenomALC Consortium to conduct this study with Australian colleagues as well as clinicians and researchers from the USA, UK, Germany, Switzerland and France.
"In Sydney, we will recruit hundreds of participants over the next three years through the clinics at four hospitals - Royal Prince Alfred, Liverpool, Concord and Fairfield. Half our group will have cirrhosis and the other half, the control group, will have been heavy drinkers for 10 years but be free of liver disease."
