A person’s red blood cells may carry an unexpected warning that the liver is under stress.
Scientists at The University of Toledo have found that these cells behave differently when bile acids build up in the bloodstream, potentially offering a fast way to detect hidden liver problems.
Liver disease is often difficult to catch early because the organ can continue working even after damage has begun. Many people do not experience clear symptoms until the condition has become more advanced.
The liver performs hundreds of tasks needed to keep the body functioning. Among them, it produces bile, a digestive fluid that helps break down fats and allows the body to absorb vitamins such as A, D, E and K.
Bile contains substances called bile acids. After being produced by the liver, they normally move through the bile system and intestine and are largely recycled back to the liver.
When this normal process is disrupted, bile acids can spill into the bloodstream. This can happen when the liver is damaged or when the flow of bile is blocked.
High levels of bile acids in blood are called cholemia. The problem is that people can have elevated levels without feeling sick, particularly early in the course of liver dysfunction.
Standard blood tests do not routinely include bile acids. Doctors may instead look at liver enzymes, bilirubin and other measurements that provide information about liver injury or function.
Those tests are valuable, but researchers say bile acids can rise before some of the more familiar warning signs. This raises the possibility that doctors are missing an early opportunity to investigate liver problems.
Dr. Matam Vijay-Kumar and Sadhana Kumari at The University of Toledo discovered a possible new way to identify high bile acid levels indirectly. Their finding came from studying red blood cells rather than the liver itself.
Red blood cells have flexible outer membranes that allow them to squeeze through tiny blood vessels. The researchers expected bile acids to weaken these membranes and make the cells more likely to rupture.
The experiment produced the reverse result. Red blood cells exposed to high bile acid levels became harder to break apart.
The researchers first saw the effect in several types of mice that naturally developed elevated bile acids. They then tested whether the same pattern could be found in people with liver disease.
The human study included 23 patients with cholestatic liver disease at the University of Toledo Medical Center. Their blood was compared with samples from 23 people of similar age and sex who did not show signs of liver disease.
Again, the red blood cells from people with elevated bile acids were more resistant to breaking under osmotic stress. This difference gave the researchers a measurable signal that could potentially be turned into a rapid screening test.
Further investigation showed that high bile acid exposure changed the fats in the red blood cell membrane. The cells accumulated more cholesterol while losing some phospholipid, another important part of the membrane.
This changed balance made the membrane more rigid. That stiffness appears to explain why the cells responded differently during the laboratory test.
The potential screening method requires only a very small amount of blood. Vijay-Kumar said about four microliters could be added to a special solution, with an answer potentially available in 10 to 20 minutes.
This could make the approach attractive for routine health care if it performs well in larger studies. A small additional sample might be collected alongside blood already being taken for tests such as blood glucose.
The researchers stress that the test would be a screening tool rather than a diagnosis. An abnormal result would tell a doctor that further investigation of the liver and bile system may be appropriate.
This distinction is important because elevated bile acids can have several causes. A screening test cannot by itself determine whether a person has fatty liver disease, a blocked bile duct, drug-related injury or another condition.
The team sees particular potential in pregnancy. Intrahepatic cholestasis of pregnancy can cause bile acid levels to rise and, in severe cases, can increase risks for the developing baby.
Because early stages may not always be obvious, rapid identification of high bile acids could potentially help doctors decide who needs more detailed testing and closer monitoring. The researchers also note that elevated bile acids occur in many other clinical conditions.
The study was published in the American Journal of Physiology—Gastrointestinal and Liver Physiology. The University of Toledo has filed a patent application for the rapid screening method.
The discovery has an appealing simplicity: instead of directly measuring bile acids with a more specialized laboratory test, researchers examine how a tiny amount of blood behaves under controlled conditions. That could potentially make screening quicker and easier.
Still, the evidence is preliminary. The human study included just 23 liver disease patients and 23 comparison participants, which is far too small to establish how well the test would perform in the general population.
People with other illnesses may also have changes in red blood cell membranes, and future studies must determine whether those conditions could confuse the results. Researchers will also need to establish the best cutoff for deciding when a test should be considered abnormal.
Another important question is whether routine screening for bile acids actually leads to earlier treatment and better health outcomes. Detecting a biological change is useful only if doctors know what follow-up is needed and patients benefit from acting on the result.
Overall, the study offers a clever new way to look for a problem that is often invisible in its early stages. If larger trials confirm its accuracy, the behavior of ordinary red blood cells could become an early signal telling doctors that the liver needs a closer look.
Source: The University of Toledo.
