Simple Whole-Blood Screen Identifies Elevated Bile Acids Linked to Liver Disease

Liver disease can progress silently until treatment options become more limited. Routine blood panels measure markers such as cholesterol, bilirubin, and triglycerides but typically do not include bile acids, which can signal early hepatic stress. As a result, asymptomatic bile acid elevations may go undetected, including in cholestatic disorders and some pregnancies. New findings demonstrate a rapid whole-blood assay that can identify elevated bile acids before conventional markers rise.

The University of Toledo (Toledo, OH, USA) has developed a simple red blood cell (RBC) lysis test to screen for elevated bile acids using whole blood. The approach targets cholemia, a spillover of bile from the liver into the bloodstream that can precede rises in standard liver injury markers. Investigators describe the concept as a first-line screen to alert clinicians when further hepatic evaluation is warranted.

Mechanistically, bile acids interact with lipids in cell membranes. Elevated exposure drives RBC membranes to accumulate more cholesterol while losing phospholipid, altering the cholesterol-to-phospholipid ratio and increasing membrane rigidity. Counter to prior expectations of fragility, the stiffened RBCs become more resistant to osmotic stress, a property the assay reads out as reduced hemolysis.

The findings were consistent across multiple genetic mouse models of spontaneous cholemia and in human testing. Blood samples from 23 patients with cholestatic liver disease treated at the University of Toledo Medical Center showed the same RBC resistance pattern when compared with 23 age- and gender-matched individuals without signs of liver disease. The screening method consistently distinguished patients with elevated bile acids from those without.

The work was recently published in the American Journal of Physiology — Gastrointestinal and Liver Physiology. Human sampling was conducted at the University of Toledo Medical Center in collaboration with UToledo Health.

A positive screen is not diagnostic; rather, it signals when additional workup may be timely, potentially enabling dietary changes, closer monitoring, or earlier identification of liver dysfunction or injury. Operationally, the team notes that when blood glucose is drawn, an extra 4 microliters can be placed into solution for a readout in 10 to 20 minutes. 

The researchers highlight broader relevance, including intrahepatic cholestasis of pregnancy, where bile acids at or above 40 micromolar raise fetal risk, and other settings such as drug-induced liver injury in which bile acids often rise but are not routinely measured. The UToledo Technology Transfer Office has filed a patent application, “Rapid Screening for Elevated Bile Acids Using Whole Blood,” application number 18844313.

“The majority of liver diseases are associated with elevated bile acids. This first-line screening is very critical,” said Sadhana Kumari, a research assistant in the Department of Physiology and Pharmacology and co-first author of the publication at The University of Toledo.

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