World-first discovery of protein brings hope for liver disease

Professor Jacob George and Doctor Mohammed Eslam at the Westmead Institute have shown that variations in the interferon lambda 3 protein cause tissue damage in the liver.
Professor Jacob George and Doctor Mohammed Eslam at the Westmead Institute have shown that variations in the interferon lambda 3 protein cause tissue damage in the liver.

In a world-first discovery, scientists at Sydney’s Westmead Institute for Medical Research have identified a protein that causes liver fibrosis (scarring), paving the way for new treatments for liver disease to be developed.

The international team, led by Professor Jacob George (the head of gastroenterology and hepatology at Western Sydney Local Health District) and Dr Mohammed Eslam at the Westmead Institute, has unequivocally shown that variations in the interferon lambda 3 (INLF3) protein are responsible for tissue damage in the liver.

The research team had previously identified that the common genetic variations associated with liver fibrosis were located on chromosome 19 between the IFNL3 and IFNL4 genes.

Building on this research in their latest study, the team analysed liver samples from 2000 patients with Hepatitis C, using state-of-the art genetic and functional analysis, to determine the specific IFNL protein responsible for liver fibrosis.

The research, which is published in the prestigious Nature Genetics journal, demonstrated that following injury, there is increased migration of inflammatory cells from blood to the liver, increasing IFNL3 secretion and liver damage.

Notably, this response is determined to a great extent by an individual’s inherited genetic makeup.

Prof Jacob George said it was a significant outcome that would help predict the risk of liver disease for individuals, enabling early intervention and lifestyle changes.

“Liver disease is now the fifth most common cause of death in Australia, affecting six million Australians,” he said.

“We have designed a diagnostic tool, based on our discoveries, which is freely available for all doctors to use, to aid in predicting liver fibrosis risk.

“This test will help determine whether an individual is at high risk of developing liver fibrosis, or whether a patient’s liver disease will progress rapidly or slowly, based on their genetic makeup.

“This important discovery will play a vital role in reducing the burden of liver disease in the future.”

The full research paper is available online at Nature Genetics.

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