New Imaging and Blood Biomarkers Advance Early Detection of Liver and Kidney Fibrosis

Researchers have developed new noninvasive biomarkers that could improve the early detection and monitoring of fibrosis in the liver and kidneys. A new FAP-Index blood test could significantly improve how doctors identify people at risk of serious liver damage caused by metabolic fatty liver disease, while a molecular imaging test can noninvasively detect kidney fibrosis from a urine sample and accurately differentiate mild and severe disease. Additionally, measuring liver stiffness using magnetic resonance elastography (MRE) may help track disease severity and progression in people with Gaucher disease.

The FAP-Index, developed by researchers from the Centenary Institute, combines a simple blood test measuring fibroblast activation protein (FAP) with routinely collected clinical information to generate a more precise assessment of a patient's risk of liver scarring. FAP is a biomarker directly involved in the biological process that drives fibrosis. In a study published in the Journal of Gastroenterology and Hepatology, the team found that adding the FAP-Index to existing first-line blood test risk scores reduced uncertain results by up to 70% compared with current screening tools alone.

Metabolic fatty liver disease affects about 1 in 3 Australians, with cases projected to increase by 25% to more than 7 million by 2030. The condition often has no symptoms in its early stages but can progress to liver scarring (fibrosis) and eventually to liver cirrhosis and liver failure. Current first-line blood test risk scores often produce uncertain results, leading to unnecessary specialist referrals and costly follow-up investigations. Unlike many existing scoring systems that rely on indirect markers of liver injury, the FAP-Index incorporates a protein that plays a direct role in the scarring process. The FAP test itself is straightforward and can become adapted for high-throughput or point-of-care settings, making it suitable for widespread clinical use.

In a separate study published in Science Translational Medicine, scientists led by Zhou Jiaguo, PhD, professor of pharmacology at Sun Yat-sen University in China, developed a new biomarker test that can noninvasively detect kidney fibrosis from a urine sample. The test could accurately differentiate between mild and severe disease, something that is not yet possible with the diagnostic methods available today. Chronic kidney disease affects approximately 12% of the global population, with rates steadily rising as the world's population ages. Characterized by the excessive formation of scar tissue, kidney fibrosis is a hallmark of chronic kidney disease that causes the progressive impairment of kidney function, eventually leading to end-stage renal disease that requires dialysis or transplantation.

The researchers identified two biomarkers specific to kidney fibrosis: the transglutaminase 2 (TG2) enzyme and its substrate, lysyl oxidase–derived allysine (LysAld), which are both upregulated during the formation of fibrotic kidney tissue. They developed a fluorescent reporter that binds to LysAld in the kidney and is then cleaved by TG2, turning on its fluorescence. Higher biomarker levels result in a stronger signal, providing an indication of how advanced fibrosis is in the patient's kidneys. In a small cohort of 35 participants, the molecular imaging test could distinguish patients with kidney fibrosis from healthy controls with 84% sensitivity and 94% specificity. In addition, the test could differentiate mild and severe cases of fibrosis, with results confirmed with histological imaging. In contrast, traditional clinical measurements such as glomerular filtration rate, serum creatinine, and blood urea nitrogen were not able to classify patients according to the severity of the condition.

In a third study published in Molecular Genetics and Metabolism, researchers evaluated whether liver MRE could be used to track disease severity over time in people with Gaucher disease. Gaucher disease is caused by a lack of functional glucocerebrosidase (GCase), an enzyme that breaks down a fatty molecule called glucocerebroside. Without enough functional GCase, glucocerebroside builds up in certain cells, which can then accumulate in tissues, including the spleen, liver, and bone marrow, contributing to a range of disease symptoms. The researchers retrospectively analyzed data from 42 people with Gaucher disease, whose mean age was 30.9 years, who underwent at least one MRE assessment from 2019 to 2025 at the Children's Hospital of Philadelphia. Almost all participants (90.5%) were diagnosed with Gaucher disease type 1, while four people had type 3 disease. The same percentage, 90.5%, were receiving either enzyme replacement therapy or substrate reduction therapy at the time of their last evaluation.

Overall, researchers found a small but statistically significant association between liver stiffness measured by MRE and GD1-DS3 scores, with greater liver stiffness associated with greater disease severity. Higher liver stiffness was associated with more severe disease, with each 1 kilopascal (kPa) increase in stiffness corresponding to an average 0.53-point increase in the GD1-DS3 score. The association remained similar after excluding patients with type 3 Gaucher disease. Liver stiffness measurements were generally below levels typically associated with advanced scarring or cirrhosis, suggesting that MRE may detect subtler liver changes related to Gaucher disease before overt chronic liver disease develops. Importantly, liver stiffness remained associated with disease severity after accounting for time, suggesting MRE may provide information beyond routine laboratory tests and measurements of liver and spleen size.