Common virus may play a role in ICP development, study finds
Human cytomegalovirus molecules may predict risk
Infection with human cytomegalovirus (HCMV), a common and usually harmless virus, may play a role in the development of intrahepatic cholestasis of pregnancy (ICP), a study found.
Measuring levels of several HCMV genetic molecules allowed researchers to accurately distinguish women with ICP from those without, suggesting that these may be useful diagnostic markers of ICP.
The study, “Clinical Potential of HCMV-Encoded Serum miRNAs in Predicting Intrahepatic Cholestasis of Pregnancy: A Retrospective Analysis,” was published in the Journal of Medical Virology.
Bile is a digestive fluid produced in the liver and transported to the intestines through a series of tubes called bile ducts. Cholestasis refers to a condition characterized by slow or stalled bile flow, which can result in bile accumulating in the liver and leaking into the bloodstream, leading to liver damage and other cholestasis symptoms, such as itching.
ICP is a form of cholestasis that can develop during the later stages of pregnancy, posing potential risks for the mother and the fetus. The causes of ICP are poorly understood. It’s mainly diagnosed by looking for elevated levels of bile in the blood, but this approach is limited in its ability to make timely and accurate diagnoses.
Analyzing molecules for a connection
HCMV causes a lifelong infection. Once the virus enters the body, it remains present indefinitely. While most people have been infected with HCMV, the virus typically does not cause serious problems. Exceptions include people with weakened immune systems and cases in which the virus is transmitted from the mother to the fetus. This often causes abortion or developmental defects.
Scientists have discovered in recent years that HCMV and other viruses can produce microRNA (miRNA), tiny pieces of genetic material that target specific genetic molecules derived from genes and serve as a template for protein production. In the case of viral miRNAs, they can regulate the production of proteins coded by viral and/or host genes.
More than two dozen different HCMV miRNA molecules have been identified, but whether these are associated with human diseases, such as ICP, is largely unclear.
A team of scientists in China investigated whether there is any association between HCMV miRNA levels and the development of ICP.
To that end, they analyzed blood samples from 151 pregnant women with ICP (average age 30.15) and 158 age-matched pregnant women without ICP or any other pregnancy complications. All women were seen at a single Chinese hospital.
“This study represents the first report on the … profiles of HCMV‐encoded miRNAs in the bloodstream of [pregnant people with ICP],” the researchers wrote.
The team found that six types of HCMV miRNA — hcmv‐miR‐UL22A‐5p, hcmv‐miR‐UL112‐5p, hcmv‐miR‐US4‐3p, hcmv‐miR‐US4‐5p, hcmv‐miR‐UL148D, and hcmv‐miR‐US25‐2‐5p — were present at significantly higher levels in women with ICP.
Statistical analyses adjusted for potential influencing factors showed that elevated levels of three of these miRNAs — hcmv-miR-UL112-5p, hcmv-miR-US4-5p, and hcmv-miR-US25-2-5p — were independent risk factors of ICP, being significantly associated with a 1.8 to 2.5 times higher chance of ICP.
The researchers also found statistical associations between all or most of these miRNAs and established markers of liver damage, including liver enzymes and bile acids, the main components of bile.
Further analyses on these miRNA targets suggested that the miRNAs may modulate the activity of human genes that help regulate liver health and that have been associated with pregnancy complications and fetal growth restriction.
To assess the utility of the six HCMV miRNAs as diagnostic markers, the researchers calculated the area under the curve (AUC), a statistical measure that assesses how well a given test (in this case, miRNA levels) can distinguish between two groups (in this case, women with or without ICP). AUC scores can range from zero to one, with higher numbers indicating better accuracy.
For each of the six individual miRNAs, AUC values ranged from about 0.71 to 0.78. Analyzing all six miRNA molecules collectively yielded better discriminative accuracy, with an AUC of 0.81, meaning that the test could distinguish women with ICP from those without with an accuracy of 81%.
The scientists noted that the study was limited to analyses of patients at a single center, so further work will be needed to validate and expand upon the results. Nonetheless, they said the data lend support to the idea that HCMV may play a role in the development of ICP, and HCMV miRNAs may be useful diagnostic markers.
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