8 July 2019
People with chronic hepatitis B virus (HBV) infection are at high risk of developing hepatocellular carcinoma — the most common form of liver cancer. Despite the availability of an HBV vaccine, there is currently no effective treatment for chronic HBV infection.
Michael Bouchard and co-workers at the Drexel University College of Medicine in Philadelphia, US, have now identified a host of new drug targets for chronic HBV infection using state-of-the-art techniques. They identified severely altered metabolites and metabolic pathways in hepatitis B-infected rats, which could help guide the design of new therapies for alleviating the infection that affects nearly 240 million people worldwide.
HBV primarily affects the liver, an organ with vital roles in many metabolic processes, including amino acid and lipid metabolism. The researchers suspected that HBV may cause distinct changes in the expression levels of metabolites, and that the tipping of the balance is what causes the malady.
To hone in on these metabolites, the researchers collected samples from liver cells 24 and 48 hours after infecting rats with an adenovirus expressing HBV or the HBV X protein (the requisite part of HBV needed to cause chronic HBV infection). They then profiled the expression levels of 369 metabolites in the samples.
They found that 24 and 48 hours after infection, 47 and 139 metabolites were significantly altered by HBV, whereas 28 and 149 metabolites were significantly altered by the HBV X protein. Among these metabolites, seven were significantly altered by both HBV and the HBV X protein. These alterations, if reversed, may help restore the balance of the liver and, subsequently, alleviate or treat chronic HBV infection.
Most of the severely altered metabolites were associated with glucose, phospholipid and fat metabolism. The result shows that, by analysing the expression levels of metabolites and the metabolic pathways they are involved in, there may be key compounds that can be targeted in treating diseases.
The researchers noted in their paper that a complete understanding of the cellular consequences of an HBV infection is critical, and that their results represent an important step towards the identification of novel therapeutic targets for the treatment of HBV. They are hopeful that with new profiling technologies, other groups may further expand the knowledge base of metabolic alterations.
Lamontagne, R. J., Casciano, J. C. and Bouchard, M. J. A broad investigation of the HBV-mediated changes to primary hepatocyte physiology reveals HBV significantly alters metabolic pathways. Metabolism Clinical and Experimental 83, 50–59 (2018). | article