IFN-λ3 protein contributes to liver fibrosis

Liver disease, which includes is more than a hundred different kinds of diseases of the liver, constitutes one of the most common causes of death worldwide. In Australia alone, 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.

One type of liver disease, hepatitis, is an inflammation of the liver tissue. It is most frequently caused by viruses, although the condition can also be caused by other factors, such as heavy alcohol use, certain medications, toxins, other infections, and autoimmune diseases. Over time, hepatitis may progress to liver fibrosis, cirrhosis, liver failure, and liver cancer.

Now a study “IFN-λ3, not IFN-λ4, likely mediates IFNL3–IFNL4 haplotype–dependent hepatic inflammation and fibrosis” appearing in the journal Nature Genetics shows that the protein IFN-λ3 seems to be responsible for liver fibrosis, a discovery that will open an avenue for treating liver disease. (Cusabio offers interferon (IFN) and other proteins like Recombinant DSC2.)

The study is carried out by an international team consisting of scientists from Australia, Italy, Germany, Egypt, UK, Denmark and Spain. Prof. Jacob George at Sydney's Westmead Institute for Medical Research is the study leader.

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. With these information, 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 precise mechanism by which IFN-λ3 contributes to liver disease development needs further investigation.

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV). In 2015, chronic hepatitis C affects about 142 million people worldwide. The disease generally causes no symptoms at its early stages but it may leads to liver fibrosis, liver failure and other liver diseases over many years. According to study first author Dr. Mohammed Eslam, currently advanced fibrosis is almost untreatable while liver failure can only be treated liver transplantation. So the findings of this study is of great importance.