Current liver research: A rationale for the more severe course of HDV-associated liver disease

8 September 2015

Approximately 20 million people worldwide are chronically infected with the hepatitis Delta virus (HDV). HDV alone is not functional. It is a defective virus which needs the envelope proteins of the hepatitis B virus (HBV) in order to proliferate and to complete its viral life-cycle. A co-infection with hepatitis D can worsen chronic hepatitis B and significantly increases the risk that the patient will develop advanced cirrhosis and liver cancer. But why?

The research group led by Prof. Dr. Maura Dandri and Dr. Marc Lütgehetmann, both SFB principal investigators (project A8), developed an infection model, suitable to investigate the interaction between the hepatitis D virus and human liver cells. For the first time, the scientists could show that the innate immune response varies widely, depending on whether the cells are solely infected with HBV or simultaneously with HBV/HDV. While the hepatitis B virus alone apparently is capable of remaining almost undetected and evading the immune defense, the hepatitis D virus activates a number of genes that alert the immune system. For example, the concentration of cytokines that promote liver inflammation and scarring considerably increased. The establishment of HDV infection provoked a clear enhancement of the antiviral state of the human hepatocytes, providing for the first time a rationale for the more severe disease course of chronic HBV/HDV co-infection as compared to HBV mono-infection. Research results have been published in the Journal of Hepatology (Giersch et al. 2015).

Giersch K, Allweiss L, Volz T, Helbig M, Bierwolf J, Lohse AW, Pollok JM, Petersen J, Dandri M, Lütgehetmann M

Hepatitis Delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection
J Hepatol. 2015 Aug;63(2):346-53. doi: 10.1016/j.jhep.2015.03.011. Epub 2015 Mar 17.

Further Information:

Read about the CRC project A8 led by Prof. Maura Dandri and Dr. Marc Lütgehetmann „Hepatitis D virus: pathogenesis and interaction with innate immune system“.

In a previous study, the researchers demonstrated that the hepatitis D virus may well survive for weeks alone in human liver cells (Giersch et al. 2014). This is evidence that the pathogen is more persistent and viable as virologists and physicians previously assumed. The hepatitis D virus can survive without the hepatitis B virus and even be re-activated after re-infection with HBV. Please find a video and more details about this research here.