Bile acids stay high in biliary atresia patients after Kasai procedure
Findings position bile acids as possible prognostic biomarker, therapeutic target
Bile acids, which aid the fat-digesting functions of bile fluid, remain elevated in the blood and urine of adult biliary atresia patients whose bile flow normalized after corrective surgery, a study shows.
The findings position bile acids as a possible prognostic biomarker or therapeutic target for biliary atresia patients for whom a standard Kasai portoenterostomy was initially successful.
“These fundamental data … suggest the potential value of investigating bile acid profiles in patients with biliary atresia,” the researchers wrote in “Bile acid profiles in adult patients with biliary atresia who achieve native liver survival after portoenterostomy,” which was published in Scientific Reports.
Bile is a digestive fluid produced in the liver and sent to the intestines via a series of tubes called bile ducts. In biliary atresia, bile ducts outside the liver are blocked or absent, causing bile to build up in the liver, which results in damage and bile leaking into the bloodstream.
A Kasai portoenterostomy is a surgical procedure and first-line treatment of biliary atresia. It’s intended to reestablish bile flow out of the liver. While it helps delay needing a liver transplant, most patients still develop extensive liver damage and eventually requires one.
High bilirubin levels after a Kasai procedure suggest continuing problems with bile flow (cholestasis) and a higher likelihood of needing a liver transplant. Bilirubin is made when red blood cells are broken down and incorporated into bile. Normalized bilirubin levels indicate successful bile drainage, but these outcomes aren’t easy to predict.
“In recent years, bile acids have received increasing attention as a marker of the long-term prognosis and a potential therapeutic target in patients who have achieved normalized bilirubin levels after Kasai portoenterostomy,” the researchers wrote.
Analyzing bile acids in biliary atresia
Previous research found that lower levels of bile acids in the blood of patients with normalized bilirubin after a Kasai procedure were linked to better liver parameters and higher rates of liver transplant-free survival.
Here, the scientists analyzed the bile acid composition in the blood and urine of 10 adults with biliary atresia whose bilirubin had normalized after surgery and 10 healthy adults who served as controls. Half the patients were being treated with ursodeoxycholic acid (UDCA), a nontoxic bile acid that helps bile flow through the liver. Despite normal bilirubin levels, biliary atresia patients showed clinical indicators suggestive of mild liver fibrosis, or scar tissue buildup that can impair function.
Total bile acids with or without UDCA were significantly elevated in the blood of the biliary atresia patients over the healthy people.
Bile acids come in different forms. Primary acids are produced directly in the liver and can exist on their own (unconjugated) or bound to other molecules (conjugated). Bile acids are conjugated before they are secreted to form bile salts that are more water soluble and better able to perform their fat-digesting functions.
Primary bile acids were significantly increased in patients’ blood relative to controls, especially conjugated ones. No significant differences were observed based on whether patients had been treated with UDCA.
Bile acid profiles typically associated with advanced liver cirrhosis, where the liver is permanently scarred and significantly damaged, weren’t seen in the patient group.
Once bile salts reach the intestines, they are modified by gut bacteria to form secondary bile acids. Secondary bile acids excluding UDCA were significantly lower in biliary atresia patients than healthy controls. The unconjugated bile acid DCA was significantly diminished.
Bile acids in urine
Total bile acid levels were also significantly elevated in the urine of biliary atresia patients, but no significant difference were observed for total bile acids excluding UDCA.
There were no significant differences between groups regarding primary and secondary bile acids. An individual unconjugated bile acid called GCA-3S was significantly higher in the urine of biliary atresia patients.
Moreover, blood levels of the conjugated primary bile acid GCDCA were strongly correlated with a biomarker of liver fibrosis called M2BPGi. No other bile acids were associated with fibrosis markers.
The findings indicate “bilirubin normalization after Kasai portoenterostomy does not lead to complete improvement in the excretion and metabolism of bile acids,” wrote the researchers, who said “ongoing clinical trials are expected to clarify the role of bile acids in biliary atresia.”
Mechanisms underlying the congestion of bile acids are still being explored, but the researchers said impairments in bile acid transport proteins may be involved. They also said “it is worthwhile to pursue additional validation” of the role of these proteins in biliary atresia by analyzing the genes that code for bile acid transporters in the liver and enzymes responsible for bile acid production.
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