New tests aim to detect liver disease earlier — without a biopsy
By A.J. Hostetler
Hepatologists at VCU Health are studying faster, safer ways to detect liver disease without a liver biopsy.
People with viral hepatitis, obesity, diabetes or a history of heavy alcohol use may need tests to check their liver health.
A biopsy remains an important diagnostic tool, but it is invasive and carries small risks, including pain, bleeding, infection and, rarely, death. Patients and physicians would prefer accurate, affordable tests that do not require inserting a needle between the ribs or into the abdomen to remove liver tissue.
“Getting a diagnosis early can help people change diet, stop harmful medicines or alcohol, and start treatments that slow the disease. Non-invasive tests are faster, safer and easier to repeat over time, so it’s more likely that people would get checked and treated sooner,” said Virginia Commonwealth University hepatologist Arun Sanyal, M.D., who directs the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health.
Sanyal is a leader in the field of evaluating noninvasive tests, or NITs. He heads the Foundation for the NIH Biomarkers Consortium’s NIMBLE program, which evaluates how well biomarkers detect liver disease and could help move them toward regulatory approval.
Accurate biomarkers could make it easier for patients to join clinical trials, reduce study costs and speed the development of new treatments. Many could also be ordered in a doctor’s office.
What noninvasive tests are available?
One widely used test is the FIB-4 index, created 20 years ago by a team led by VCU Health hepatologist Richard Sterling, M.D. The test uses a patient’s age and results from three routine blood tests to estimate the amount of liver scarring. Primary care physicians can use an online calculator to determine whether a patient may need additional testing.
Sterling, now chief clinical officer for the VCU liver institute and chief of hepatology for VCU Health, said his concern about liver biopsies helped inspire the test.
“During my training and early in my career, I thought, ‘Who had the bright idea to stick a large needle into a very vascular organ?’ There had to be a better way.”
Because it is simple and uses common blood tests, FIB-4 is often the first step in evaluating people with metabolic dysfunction-associated steatotic liver disease, or MASLD. It can help identify people who may have advanced liver scarring and estimate their risk of future health problems.
Other blood tests include FibroScan, sometimes called FibroSure in the United States. It combines several blood markers to estimate liver scarring.
The enhanced liver fibrosis, or ELF, test measures three proteins linked to scarring. Recent research led by Sanyal suggests that an ELF score below 9.00 may help rule out important scarring in people with MASLD. Scores of 9.80 or higher may indicate advanced scarring, while scores of 11.30 or higher may suggest cirrhosis. Doctors may use ELF with other tests to guide diagnosis and treatment.
Other blood-based tests include OwLiver, which measures metabolites; NIS2+, which measures two biomarkers and accounts for sex; and M2BPGi, a newer marker being evaluated in several countries.
Imaging tests can also measure liver stiffness or fat. FibroScan and shear-wave ultrasound use sound waves to assess stiffness, which can indicate scarring. Magnetic resonance elastography, or MRE, uses MRI to map liver stiffness and is highly accurate but more expensive. MRI‑PDFF measures liver fat and is widely used in clinical trials.
No test is perfect. A biopsy also samples only a small part of the liver, so doctors may combine several tests to get a fuller picture of a patient’s disease.
Hepatologists sometimes combine tests to improve accuracy. Sanyal helped develop the Agile 3+ and Agile 4 scores, which combine FibroScan results with blood-test data to estimate the severity of liver disease.
Beyond diagnosis, researchers are studying whether noninvasive tests can predict a patient’s future health and track whether treatment is working. If validated, these tests could reduce the need for biopsies in clinical trials, speed drug development and bring new treatments to patients sooner.
Researchers are also studying breath, urine and saliva tests. These approaches are still experimental but could offer additional simple, painless ways to look for liver disease.
In a 2024 article reviewing the latest tests, Sterling and his colleagues concluded that the best approach may depend on the cause of liver disease. They also found that combining tests often works better than using a single test.
A recent study illustrates the potential of combining multiple sources of information. In a July 20 paper posted online by Nature Communications before peer review, researchers including Sanyal and VCU’s Amon Asgharpour, M.D., described a computer model that combines health records, routine blood tests and ultrasound results to estimate a patient’s risk of liver scarring.
In a study of 209 patients, including VCU Health volunteers, the model performed especially well at identifying more advanced liver scarring. In a second study of 194 VCU Health volunteers, the model was linked to fewer unsuccessful biopsy attempts when it identified patients at high risk for MASH.
What is VCU Health doing to improve these tests?
Sanyal leads several of these efforts, and VCU Health patients have participated in the clinical trials. His work includes validating MRI-PDFF and MRE to measure liver fat and scarring, as well as testing combinations of imaging and blood markers that could reduce the need for biopsies.
Sanyal also co-leads multicenter studies that evaluate groups of biomarkers and computer algorithms for diagnosing NAFLD and NASH.
Many of these tools — including FibroScan, MRI-PDFF, ELF and FIB-4 — are already used in medical care. Others remain under study. VCU researchers are testing new blood tests, ultrasound machines, MRI techniques and computer tools that could help doctors detect liver disease and liver cancer earlier.
One study uses computer programs to examine old liver biopsy images and predict how patients may do. Another uses special MRI scans to measure liver fat and scarring and compares the results with biopsy and ultrasound findings.
Before these tools become part of standard care, researchers need larger studies with more diverse patients and longer follow-up. If the tests prove accurate across different groups, more people could be screened and treated earlier without an invasive biopsy.
What you should know
Patients concerned about their liver health should discuss screening options with their primary care physician. If a biopsy is recommended, they can ask whether noninvasive tests or a combination of tests could provide useful information first.
Those seeking patient care may contact VCU Health toll-free at 833-828-5487.