Biomarkers of inflammation could help identify ICP, study finds
2 whole-body markers may complement traditional biomarker testss
Women with intrahepatic cholestasis of pregnancy (ICP), the most common pregnancy-related liver complication, have significantly higher scores of two whole-body inflammation biomarkers than women without pregnancy complications, a study showed.
Scores of these two markers, systemic immune-inflammation index (SII) and the neutrophil-to-lymphocyte ratio (NLR), were able to discriminate between women with IPC and those without it with an accuracy of nearly 60%.
“SII and NLR offer a cost-effective and rapid means of diagnosing ICP, potentially complementing or surpassing traditional biomarkers like bile acid levels and liver function tests,” the researchers wrote.
The study, “Are Systemic Inflammation Markers Reliable for Diagnosing Intrahepatic Cholestasis of Pregnancy? A Retrospective Cohort Study,” was published in the American Journal of Reproductive Immunology.
Cholestasis occurs when the flow of bile, a digestive fluid that helps break down fatty molecules and proteins, from the liver to the intestines slows or stops. This can lead to bile accumulation in the liver, damaging the organ, and bile leakage into the bloodstream, which can cause symptoms such as itching.
Complications for mother and baby
ICP is a form of cholestasis that develops during pregnancy. While symptoms can resolve on their own when the pregnancy ends, ICP is linked to an increased risk of complications for both mothers and their babies, making early diagnosis crucial.
The condition is diagnosed by measuring blood bile acid levels and checking how well the liver is working based on blood levels of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
“Although new biomarkers specific to the disease have been identified, most of them, including the measurement of [total bile acid] levels, are time-consuming and expensive,” the researchers wrote. They set out to evaluate whether four whole-body, or systemic, inflammation markers, based on blood cell counts, had any diagnostic potential for ICP.
That idea was based on the fact that cholestatic liver disease and elevated bile acids trigger inflammation, as well as on evidence suggesting that “measuring the ratio of cell types in the blood … may provide prognostic and diagnostic insights for diseases related to chronic low-grade inflammation,” the researchers wrote.
The tested markers were the systemic immune-inflammation index, the systemic inflammation response index, the pan-immune inflammation value, and the neutrophil-to-lymphocyte ratio.
All are based on ratios or equations of counts of blood cells, such as immune-related cells like neutrophils, monocytes, and lymphocytes, and blood clot-forming platelets. They can be measured via a standard complete blood count (CBC), making these tests “more accessible and affordable” than bile acid measurements, the researchers wrote.
The team retrospectively reviewed the medical records of 242 women who gave birth at Etlik City Hospital in Ankara, Turkey. Half had ICP, while the other half had uncomplicated pregnancies and served as a control group. The median age in both groups was about 29.
As expected, blood levels of the liver enzymes AST and ALT were significantly elevated in the ICP group compared with the control group. Women with ICP also delivered babies at significantly earlier gestational ages, with significantly lower birth weights, and more frequently through cesarean section.
Women with ICP had significantly higher SII scores (median of 837 vs. 716) and higher NLR (median of 3.54 vs. 3.06) at diagnosis compared with healthy controls, suggesting an elevated inflammatory response in the ICP group.
The SII is based on an equation of the numbers of neutrophils, platelets, and lymphocytes, while the NLR is based on neutrophil and lymphocyte counts. The higher the SII or NLR value, the more inflammation in the body.
No significant group differences were detected for the other two systemic inflammation markers.
Further statistical analyses showed that the SII was able to differentiate women with ICP from those without the complication with an accuracy of 58.1%, and the NLR did so with an accuracy of 59.8%. There were no significant differences in the predictive power of these two markers.
These findings suggest that the SII and the NRL could be useful for ICP detection. But since their moderate predictive potential prevents them from replacing standard diagnostic tools, they “should be used in conjunction with traditional biomarkers,” the researchers wrote.
The team called for additional studies to verify the reliability of SII and NLR in larger and more diverse groups of patients.
“Further research is needed to explore their relationship with the severity of ICP and associated maternal and fetal outcomes, and to establish standardized protocols for their clinical use,” the researchers wrote.
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