IFN-λ3 may mediate liver fibrosis

An international team consisting of scientists from Australia, Italy, Germany, Egypt, UK, Denmark and Spain has identified a protein that is responsible for liver fibrosis, a discovery that will open an avenue for treating liver disease.

The study, led by Prof. Jacob George at Sydney's Westmead Institute for Medical Research, is published online 10 April 2017 in Nature Genetics.

Previously, the team located liver fibrosis-related genetic variations on chromosome 19 between the IFNL3 and IFNL4 (interferon-λ3 and interferon-λ4) genes. But whether IFN-λ3 or IFN-λ4 protein drives the disease is unknown. In this work, the team set out to address this question. Using multiple methods, they examined liver samples from 2000 patients with Hepatitis C and found that liver inflammation, fibrosis stage, fibrosis progression rate, liver infiltration of immune cells, IFN-λ3 expression are greater in patients with the IFNL3–IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. This suggests that it is IFN-λ3 but not IFN-λ4 that likely mediates liver inflammation and fibrosis. The IFN-λ3 protein is a naturally occurring antiviral agent and modulates functions of the immune system.

Based on these findings, doctors may be able to predict which people are at risk of developing liver disease and then take effective measures to deal with it. The team plans to further explore the mechanism by which IFN-λ3 contributes to liver disease development.

Liver disease is an umbrella term for many diseases that affect the liver. There are more than a hundred different kinds of liver disease, which constitutes one of the most common causes of death worldwide. One type of liver disease, hepatitis, is an inflammation of the liver tissue. It is most frequently caused by viruses, although there are other factors that cause the condition. Over time, hepatitis may progress to liver fibrosis, cirrhosis, liver failure, and liver cancer.

In Australia, approximately 6 million people are suffering from liver disease, putting an enormous burden on the health care system. It is imperative to develop more effective therapeutic agents for liver disease.
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