New CF study finds digestive bile acids altered in children, teens
Researchers ID distinct patterns in youth with CF-related liver disease
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Both youngsters and teenagers with cystic fibrosis (CF) have abnormal levels of bile acids, the main components of the digestive fluid bile, in their blood compared with healthy children — and these alterations were found to worsen with age — a new study reports.
The researchers also identified distinct bile acid patterns in patients with CF-related liver disease, pointing to possible signs of worsening liver involvement.
“Our data show that bile acid composition is altered in children with CF,” the scientists wrote, adding that “this difference is evident from preschool age onward.”
Further, the scientists noted that “these changes appear to aggravate with age, which could indicate an age-dependent increase in [liver] impairment.”
The study, “Alterations of bile acid composition in children with cystic fibrosis compared to healthy controls,” was published in the Journal of Cystic Fibrosis.
In CF, a faulty or missing CFTR protein leads to the buildup of thick, sticky mucus in various organs, including the lungs, pancreas, and intestines.
Mucus due to CF can build up in body’s bile ducts
As many as 15% of CF patients develop liver disease caused by the buildup of mucus in the liver and bile ducts, which are the small tubes that carry bile from the liver to the small intestine to help digest fats. If bile flow slows or stops — a condition referred to as cholestasis — bile can build up in the liver, triggering inflammation and scarring, also called fibrosis. This can become permanent, when it’s known as cirrhosis, and may lead to liver failure.
Bile is made up mostly of bile acids, but whether these bile acids are altered in children and teens with CF is unknown.
To learn more, researchers in Germany analyzed blood samples from 73 pediatric CF patients, ages newborn to 17, and compared them with samples from 100 healthy children of the same age and sex.
The researchers found that the children with CF had significantly higher overall bile acid levels in their blood than the healthy controls.
Most major bile acid subtypes were elevated in the CF patients, including those categorized as primary (produced in the liver), secondary (modified by gut bacteria), unconjugated (unattached), and conjugated (attached to another molecule, such as glycine or taurine). Conjugation increases the ability of bile acids to dissolve in water.
In particular, glycine-conjugated bile acids were significantly higher in the children with CF, whereas tuarine-conjugated bile acids were significantly lower. Both glycine and taurine are amino acids, the building blocks of proteins.
Some bile acids could distinguish between those with and without CF. Unconjugated bile acids were the most accurate (77.1% accuracy), followed by taurine-conjugated bile acids (65.8% accuracy). Other bile acid combinations also showed differences, but were less accurate, according to the researchers.
Changes in bile acid levels seen to worsen with age
Age also made a difference, the scientists found.
In the children with CF, total bile acid levels decreased from infancy to adolescence, along with conjugated and primary bile acids in particular. Infants with CF had higher levels of taurine-conjugated bile acids than their older counterparts.
In healthy children, taurine-conjugated bile acids also declined with age, but total bile acid levels stayed relatively stable across age groups. Differences between the children with CF and healthy peers were most noticeable in all age groups, except for infancy.
The patients who had advanced CF-related liver disease (aCFLD) showed significantly higher levels of secondary bile acids compared with those without advanced liver disease. Specific bile acids — glycine-conjugated lithocholic acid, lithocholic acid, glycine-conjugated deoxycholic acid, and deoxycholic acid — were also elevated. Similar changes were seen in children with worse liver ultrasound scores.
While bile acids showed a tendency to rise in both groups, in the aCFLD group, the increase was significantly greater beyond age 12, the team noted.
Adolescents with CF had especially high levels of secondary bile acids compared with healthy teens. And, in both patients and healthy children, infants had lower levels of several secondary bile acids than the older age groups.
CFTR modulator therapy linked to lower levels of 1 bile acid
Finally, children with CF who were taking a CFTR modulator therapy — approved treatments for patients of all ages — had significantly lower levels of a certain conjugated bile acid, namely, glycine-conjugated lithocholic acid, than those not on modulator treatment. However, overall bile acid ratios were similar between the two groups, the researchers noted.
“To the best of our knowledge this is the first prospective study to compare [bile acid composition] in children with CF and healthy controls,” the scientists wrote, noting that “bile acids
take an essential part in the digestive process.”
According to the team, “further studies that systematically analyse the longitudinal [over time] change of [bile acid composition] and the impact of pharmaceutical interventions are needed.”
