Noninvasive Testing Shows Promise for Assessing Fatty Liver Disease

A mix of blood-based tests and imaging could reduce the need for liver biopsies when tracking fatty liver disease progression.

Metabolic dysfunction-associated steatotic liver disease, known as MASLD or fatty liver disease, is managed and prognosed according to how advanced it has become. Determining the stage of the disease has traditionally required a liver biopsy to measure fat buildup, inflammation and scarring. Although biopsies are generally considered safe, they are still invasive and carry some risks, including bleeding, along with practical limitations. New findings from the Liver Investigation: Testing Marker Utility in Steatohepatitis, or LITMUS, study suggest that a combination of noninvasive biomarker tests may help diagnose and stage liver disease without biopsy, according to research published in The Lancet.

“For advanced liver scarring and cirrhosis, we now have tools good enough to use with real confidence,” senior author Quentin Anstee, PhD, said in a news release. “Detecting active liver inflammation remains more challenging, but promising noninvasive tests are becoming available.”

MASLD and its more serious form, metabolic dysfunction-associated steatohepatitis, or MASH, account for an increasing share of advanced liver disease around the world. An estimated one-third of people in the United States have MASLD, and 5% have MASH. As fat accumulates in the liver, it can eventually cause cirrhosis, liver cancer and other severe complications. The condition is common in people with obesity, type 2 diabetes and other metabolic disorders. With only two approved medications, Rezdiffra and Wegovy, treatment still depends largely on lifestyle changes such as weight loss and exercise.

In its earliest stages, MASLD often causes no symptoms. As it advances, symptoms such as fatigue or general malaise may appear, but they are often nonspecific, according to the Mayo Clinic. In addition to liver enzymes and scarring measurements, disease progression can be monitored through biopsy or imaging methods such as ultrasound, MRI and CT scans.

Researchers from Newcastle University and the University of Amsterdam evaluated blood biomarkers, imaging and elastography measures — a technique that uses vibrations to assess liver scarring or cirrhosis — in 1,590 patients from 37 liver centers across 13 European countries and the United States, all of whom had been diagnosed with MASLD through biopsy. They compared the performance of 30 tests with standard diagnostic criteria for MASLD and MASH, and considered any test scoring above 0.8 on a zero-to-one scale as a possible alternative to biopsy.

None of the tests met the preset threshold for diagnosing early fatty liver disease, but several showed strong results for identifying fibrosis and cirrhosis. For detecting patients at risk for MASH, SomaSignal, a blood test currently used only to monitor liver disease progression in trials, achieved the top score at 0.83. It also performed best for advanced fibrosis, scoring 0.93, followed by FibroMeter-VCTE at 0.87, Agile 3+ at 0.84 and the blood test TSP2 at 0.84. Several tests for cirrhosis assessment surpassed 0.8, with FibroMeter-VCTE leading at 0.94 and SomaSignal close behind at 0.92.

“These findings could support the selection and implementation of noninvasive testing strategies in MASLD and inform future clinical guidelines, regulatory evaluation and clinical trial design,” the study authors wrote.

To learn more about fatty liver disease, check out Hep’s Basics on MASLD and MASH.