Researchers have uncovered a biological mechanism that may explain why the risk of contracting hepatitis E virus (HEV) is higher during pregnancy, especially in its later stages.
It turns out that the natural hormonal changes associated with pregnancy may provide the virus with the right conditions to multiply more.
The study, conducted on cell cultures and rabbits, showed that high levels of the hormone “placental lactogen” during pregnancy stimulate the body to produce larger quantities of certain types of fats, creating an environment that helps the hepatitis E virus to multiply.
The findings offer a possible explanation for why infection with the virus during pregnancy, particularly in the third trimester, is associated with serious complications including liver failure, problems affecting the fetus, and an increased risk of maternal death.
Hepatitis E virus is a leading cause of acute viral hepatitis worldwide, with most cases occurring in areas with poor sanitation. While the virus can infect people of all ages, pregnant women, especially in the later stages of pregnancy, may experience more serious complications.
The mechanisms by which pregnancy makes the disease more severe remained not fully clear until the new study revealed a link between hormonal changes that occur during pregnancy and the process of viral replication.
Scott Kinney, co-author of the study and associate professor of animal science and preventive veterinary medicine at The Ohio State University, explained that the findings reveal a link between hormones, lipids, and the virus, which helps explain why hepatitis E can become a very serious illness during pregnancy.
Kush Yadav, the study's lead author and an assistant professor of animal science at Ohio State University, said that the biological processes the body needs to support fetal development may be exploited by the virus to its advantage.
The researchers focused on the hormone “placental lactogen”, the level of which rises significantly during pregnancy, and plays a role in the metabolic changes that help the body provide the energy needed for fetal growth.
The researchers found that elevated levels of this hormone lead to increased production of specific types of fatty acids and fats within the body. These compounds are naturally involved in energy storage, building cell membranes, and carrying outother vital functions.
However, in the case of hepatitis E virus, the virus can take advantage of these metabolic changes, as the fats produced by the body provide it with an environment that helps it to reproduce more efficiently.
Experiments have shown that elevated levels of oleic acid, a common fatty acid in the body, directly promote the replication of the hepatitis E virus. Researchers also found that increased production of phosphatidylethanolamine (PE), a type of lipid involved in cell membrane formation, is essential for viral replication.
The researchers not only identified the fats that the virus benefits from, but also tested what happens when the pathways responsible for producing them are disrupted.
Experiments showed that blocking these pathways led to a significant decrease in hepatitis E virus replication, suggesting the potential for targeting lipid production in developing future treatments for the infection.
Minuka Bhandari, a co-author of the study and a senior researcher in the Research and Analytical Services Unit at The Ohio State University College of Food, Agricultural and Environmental Sciences, said that using advanced lipid analysis techniques helped the team identify lipid compounds that appear to play a key role in viral replication.
Researchers believe the findings could pave the way for the development of treatments targeting the relationship between hormonal changes, fat metabolism, and hepatitis E virus replication.
These treatments may include targeting the pathways through which the body produces fat, regulating some of the metabolic changes that occur due to hormones during pregnancy, or developing antiviral drugs that disrupt its use of fats found in cells.
However, the researchers emphasize that the results still need further study, especially in humans, before determining whether this mechanism can be turned into a safe and effective treatment for pregnant women infected with the virus.
