Project ID: D2022-12
Background
Chronic liver disease (CLD) exerts a huge economic burden causing 3.5% of deaths worldwide mainly due to poor early diagnosis of the disease. COVID-19 has also contributed a moderate impact causing further burden to CLD diagnosis. Cholemia and cholestasis are pathological conditions related to liver disorders with excess of bile acids in the blood. One unique feature of cholestasis is jaundice with abnormally elevated levels of bilirubin as well as bile acids in the blood, whereas in cholemia, only bile acids but not bilirubin is elevated in the blood. While jaundice has been extensively studied and have well-established diagnosis, cholemia is largely asymptomatic in nature with no existing simple and routine methodology for the diagnosis. Currently, the gold standard for liver function test is an assay of serum alanine transaminase (ALT; aka SGPT) and measuring serum bilirubin if sera appear yellowish in color. These tests typically require symptoms to be present (e.g., jaundice), which can limit early detection and treatment options for asymptomatic cholemia. As a result, commonly used liver function tests (serum ALT) do not actually measure liver function, but rather, merely detect acute but not chronic liver injury. There is a need for highly accurate, low-cost, and sensitive test for cholemia, a clinical condition in which blood bile acid levels increase by 10-20 fold without any increase in serum ALT.
Invention Description
Researchers at the University of Toledo have developed a novel method for detecting and diagnosing cholemia. Advantageously, our assays and method are found to be accurate both in asymptomatic and symptomatic patients, and are cheap, simple, and non-invasive. Our novel method uses whole blood for accurate diagnosis and screening for cholemia by measuring erythrocytes resistance to osmotic fragility. In measuring for osmotic fragility, it was observed that mice were highly resistant to osmotic lysis further indicating that systemically elevated BA levels promote osmotic lysis resistance in vivo. The ascertainment of hemolysis resistance in the mice led to the conclusion that osmotic lysis can be used as a biomarker in patients with cholestatic liver disease because these patients exhibit higher circulating bile acids. Proof-of-concept has been addressed following testing on whole blood from mice and humans.
Applications
Advantages