Blood levels of gut protein may be marker of ICP, study finds
Xenin-25 levels more accurate marker than standard measures
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Blood levels of xenin-25, a small protein (peptide) produced in the gut, may serve as a biomarker to help diagnose intrahepatic cholestasis of pregnancy, a study showed.
Xenin-25 was significantly elevated in women with ICP compared with healthy women, and demonstrated a higher diagnostic efficacy than conventional markers of liver damage, including scores of liver scarring (fibrosis).
“The findings, indicating a link between Xenin-25, [liver] stress and fibrosis scores, support the hypothesis that Xenin-25 can function as a prognostic biomarker,” the researchers wrote. “Moreover, Xenin-25 may … also reflect underlying [disease-causing] mechanisms, suggesting a potential contributory role in the disease process.”
The study, “The evaluation of Xenin-25 levels in intrahepatic cholestasis of pregnancy and comparison with healthy pregnant women,” was published in BMC Pregnancy and Childbirth.
ICP is a form of cholestasis (the slowing or stalling of the digestive fluid bile flow from the liver to the intestines) that most often develops in the third trimester of pregnancy. It’s characterized by cholestasis symptoms, such as itching, as well as elevated levels of bile acid, the main component of the digestive fluid bile. The condition also increases the risk of complications for the mother and the fetus.
Investigating the link
Xenin-25 has been shown to promote gastrointestinal movements and contractions in the gallbladder, the organ that stores bile, to promote the release of bile to the intestines. That suggests it may contribute to bile flow, which could be particularly relevant to liver diseases such as ICP that are marked by cholestasis.
However, no research has “specifically investigated a possible link between xenin-25 and intrahepatic cholestasis in pregnancy,” the researchers wrote.
To evaluate the potential diagnostic and prognostic utility of xenin-25 in ICP, a team of researchers in Turkey analyzed data from 88 pregnant women, 44 with ICP and 44 without, who were followed at a single hospital.
Women with ICP had a significantly lower body mass index, a ratio of weight and height used as a proxy of body fat (28.14 vs. 30.56 kg/square meter), and a significantly shorter gestation time to birth (37 weeks vs. 39 weeks) than those without ICP.
Babies in the ICP group were born at significantly lower weights (2,812 g vs. 3,274 g) and had lower Apgar scores, which reflect worse overall health for the newborn, in the first and fifth minutes after birth.
The ICP group also had a significantly higher frequency of a Composite Adverse Perinatal Outcome (27.3% vs. 6.8%), a measure of adverse maternal and infant complications.
Women with ICP had significantly higher blood levels of liver damage markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and fibrinogen, and significantly lower levels of albumin, a protein produced by the liver. Blood xenin-25 levels were also significantly higher in women with ICP than in those without (48.39 vs. 20.97 picograms [pg]/mL).
The ICP group also scored significantly higher on blood-based measures to estimate liver fibrosis, FIB-4 and APRI.
Further analysis demonstrated that higher blood levels of AST, ALT, fibrinogen, and xenin-25; higher APRI and FIB-4 scores; and lower albumin levels were each significantly associated with ICP.
The researchers found similar associations between higher levels of liver damage markers and higher fibrosis scores and higher blood xenin-25 levels. “This relationship indicates that Xenin-25 levels are associated with [liver] inflammation and fibrosis markers, thereby reflecting a broader biochemical spectrum of ICP [mechanisms],” the researchers wrote.
There was no significant association between xenin-25 levels and pregnancy duration, maternal age, or fetal biological parameters.
The diagnostic potential of xenin-25 and other parameters was assessed with a statistical tool called area under the curve (AUC), with scores ranging from zero to one. The higher the AUC value, the better the ability to discriminate people with a given disease from those without.
Blood xenin-1 levels showed the strongest ability to distinguish women with ICP from those without, with an AUC value of one. Levels of ALT and AST also demonstrated a high diagnostic potential, with AUC values of 0.925 and 0.942, respectively, as well as fibrinogen (AUC of 0.903) and APRI score (AUC of 0.92).
At a cutoff value of 30.6 pg/mL, blood xenin-25 levels showed 100% sensitivity, or the ability to correctly identify pregnant women with ICP, and 97.7% specificity, or the ability to correctly rule out pregnant women without ICP.
All women with ICP were correctly classified, and one healthy woman was misclassified as having ICP. No false negatives were reported, meaning no women with ICP were misclassified as healthy.
“This study demonstrated that Xenin-25 may be a novel biomarker for the diagnosis of [ICP] and the prediction of perinatal outcomes [those around the time of birth],” the researchers wrote. “Given its high diagnostic accuracy, strong correlations, and practical measurement method, Xenin-25 may gain clinical relevance in the future.”
