Improving models of chronic hepatitis

The new mouse model could offer researchers a better platform to study chronic hepatitis, a field of research that has faced sizable hurdles due to a lack of effective small-animal models. The most severe form of viral hepatitis is chronic delta hepatitis (CDH), an infection caused by the hepatitis delta virus (HDV) that affects at least 20 million people worldwide. This disease occurs when HDV “hitchhikes” on a hepatitis B virus (HBV) as it infects an individual’s liver cells increasing the risk of cirrhosis, liver transplantation and subsequent liver cancer.

Although both infections can be prevented with vaccinations, the development of curative treatments has been hobbled by a lack of small-animal models that can accurately capture the immune response of the host. Seeking to address this roadblock, Benjamin Winer and colleagues engineered mice to express the human receptor for HDV and HBV. The receptor, called hNTCP, allowed liver cells in the mice to become infected with HDV, resulting in a more accurate representation of the HDV life cycle.

The authors tested their animal model by treating HDV-infected mice with myrcludex B (MYR GmbH), which has been granted PRIME status by the EMA, and lonafarnib (Eiger BioPharmaceuticals), two drug candidates for CDH, and found that combining both therapies suppressed viral production in the blood and liver of the mice. The improved HDV mouse model could give scientists a much-needed tool for understanding disease onset and for testing experimental HDV therapeutics, the authors say.