March 16, 2015 Print
An international research group led by scientists at the Westmead Millennium Institute for Medical Research, in developing the first genetic predictor test for liver disease, has discovered a way to determine why some patients develop rapid liver scarring (fibrosis) while others do not.
An international research group led by scientists at the Westmead Millennium Institute for Medical Research, in developing the first genetic predictor test for liver disease, has discovered a way to determine why some patients develop rapid liver scarring (fibrosis) while others do not.
The risk of fibrosis progression is determined to a great extent by an individual’s genetic makeup. This genetic test will help doctors tell patients with any type of liver disease if they have an increased risk of developing life-threatening liver scarring.
Liver fibrosis results from an excessive accumulation of tough, fibrous scar tissue and occurs in most types of chronic liver diseases such as Hepatitis B, Hepatitis C, and fatty liver. Over time this leads to cirrhosis, internal bleeding, and cancer. Severe cases may require extreme treatment such as organ transplantation.
Half of all Australians over 50 years of age have at least one type of chronic liver disease, and one in three have fatty liver disease; alarming figures which have contributed to liver cancer becoming the fastest growing cause of cancer death in Australia.
The research, published today in Nature Communications, was conducted among a large cohort of over 4000 patients and aimed to discover genetic predictors for the risk of rapid fibrosis among patients with different liver diseases.
“We found that irrespective of the cause of liver disease, variations in the gene for interferon lambda 3 [an immune system related gene] determines in part, whether patients have a risk of rapid liver scarring or not,” said Professor George, a senior author of the study.
“Patients with this ‘risky genotype’ have a high immune response to Hepatitis B, Hepatitis C and fat build-up, so when their immune system begins to fight the disease it causes inflammation of the organ which then leads to scarring, or fibrosis,” he said.
The prevalence of liver disease in Australia is expected to increase 30 per cent by 2030, in direct association with the increasing rise in obesity and diabetes, particularly in Western Sydney.
Professor Jacob George, from the Westmead Millennium Institute, says, “Western Sydney is an epicentre for obesity and diabetes, the key causes of fatty liver disease. Our location and strong links to Western Sydney mean our research is absolutely critical for managing the future health of the region.”
“The test has long-reaching implications for managing patients with liver disease. Right now doctors can’t accurately tell their patients whether they are at risk of developing rapid liver fibrosis which will require specialist treatment, or if they are in the low-risk category and a change in their lifestyle could help to improve their liver health,” he said.
This genetic test allows doctors to provide patients with a more detailed prognosis; it will provide real information to help tailor treatment and guide specific advice to patients so they can take measures to prevent further deterioration and help the liver begin to repair itself.
Importantly, it can be used as a tool for prioritising liver disease patients for more appropriate and personalised treatment. The discovery also helps researchers to develop new hypotheses with a hope of finding novel therapies.
According to Dr Mohammed Eslam, the first author, another significant finding debunks a long-standing myth that liver fibrosis is primarily a male-centric disease and that all women are of lower risk.
“It is now known from this study that if a female has the ‘risky genotype’, she actually has the same level of risk as males of developing rapid liver fibrosis,” said Dr Eslam.
“This knowledge will have significant implications for doctors diagnosing women who contract Hepatitis B, Hepatitis C viruses or who have fatty livers, and the subsequent follow up and treatment of female patients,” he said.