New tests could speed up treatment for a common liver disease

Researchers want to replace liver biopsies with blood tests and imaging to speed drug development for a common liver disease and to better predict who will get sicker and which treatments help.

“Drugs are currently approved by showing they improve the liver appearance in tissue obtained by a liver biopsy. It is then the responsibility of the drug developer to continue to study patients to show they have less clinical outcomes and progression to cirrhosis,” said Institute Director Arun Sanyal, M.D. Scientists are testing noninvasive tests to find earlier indicators that a therapy will work.

Sanyal, who is also the chair of the FNIH Biomarkers Consortium NIMBLE program, is leading the follow-up projects through the Foundation for the NIH. These efforts build on NIMBLE, a public–private partnership with the FDA, academic researchers and industry that evaluated blood-panel and imaging tools for diagnosing MASH and assessing fibrosis.

In a new Nature Medicine paper, Sanyal and colleagues outline two new initiatives: MASHtrack and the Surrogate Endpoints workstream. MASHtrack will analyze stored blood samples and liver stiffness measures from long-followed patients to see which biomarkers predict serious liver events, cirrhosis or death. The Surrogate Endpoints team will track yearly changes in those tests and link those shifts to the risk of liver-related outcomes and mortality.

The teams want to find early test changes that reflect reduced risk of outcomes. “Such changes, when produced by a drug intervention, would reflect drug-induced improvement in disease status, and thus serve as a reasonably likely surrogate endpoint for approval,” Sanyal said.

They will use careful math and statistics to deal with different lengths of follow-up, people leaving the study, and other health problems. They will also show how average or real changes in the noninvasive tests move people from low-risk to high-risk groups, or vice versa.

These projects build on NIMBLE’s findings for five blood tests and liver stiffness measures and seek to create clear NIT criteria for choosing study groups and baseline risk. If the studies show reliable links between NIT values or their change over time and clinical outcomes, regulators could accept NIT-based endpoints for accelerated approvals, and clinicians could use them to monitor patients without repeated biopsies.

If this works, drug development could be faster, fewer people would need invasive tests, and patients with MASH could get effective treatments sooner.