Genes may show the way to better treatment of hepatitis C

One of the most common causes of hepatitis A is a hepatitis C virus (HCV) infection in the liver. The disease can be treated, but not all patients are cured by the currently available treatment. New research recently published in Nature Communications shows that the response to medical treatment depends on genetic factors.

An international research group led by scientists at Aarhus University, Denmark, has found out why some patients respond to the treatment, while others do not. Variations in genes for the interferon lambda 4 protein (IFNL4) determine whether patients respond well or poorly.

“Our research shows that genetic mutations that reduce the activity of the interferon lambda 4 protein provide patients with a considerably better chance of recovering from the infection. To put it another way, a functional interferon lambda 4 protein is harmful during an infection with HCV. This is paradoxical because IFNL4 is an essential part of our immune defense against viral infections, and should therefore have a positive effect,” says Associate Professor Rune Hartmann, study co-author.

IFNL4 is a member of the family of proteins called interferons, an essential part of the immune defense against viral infections. Interferons work by activating a cellular program that combats viral infections and thereby makes the cells resistant to the virus. The research group's studies show that IFNL4 has a powerful antiviral activity in the laboratory, and behaves in every way like any other member of the interferon family. Even though IFNL4 is antiviral in the laboratory, the research also clearly shows that it has the opposite effect in patients.

The researchers have a possible explanation for this apparent paradox.”Our hypothesis is that interferon lambda 4 confuses other parts of the immune system and that HCV is able to exploit this,” says PhD student Ewa Terczynska-Dyla, who also took part in the research project.

The research results indicate that it is possible to develop new treatments for hepatitis that match the individual patient's genome. This could be medicine specifically targeting IFNL4, but could also include modifying the normal treatment, depending on whether the patients have fully functional IFNL4 genes, or have a version with either reduced activity or no activity at all.