Two Major Studies Pinpoint Non-Invasive Tests That Can Diagnose Liver Disease Without Biopsy

On Thursday, two papers landed in two journals, The Lancet and Nature Medicine, and together they offer the firmest evidence so far on a question hepatologists have wrestled with for years: which non-invasive tests can reliably diagnose and grade metabolic dysfunction-associated steatotic liver disease, known as MASLD, and its more severe form, MASH, without a liver biopsy.

Both studies belong to LITMUS, the Liver Investigation: Testing Marker Utility in Steatohepatitis programme. It is the largest international effort to evaluate diagnostic tools for liver disease, and it brought together 53 partners from academia and industry, funded through the European Innovative Medicines Initiative 2 Joint Undertaking. The main study, in The Lancet, assessed blood tests and ultrasound-based liver stiffness measurements in more than 1,500 patients, the largest international study of its kind. The companion imaging study, in Nature Medicine, looked at advanced MRI and elastography techniques in more than 350 patients.

The scale of the problem explains the effort. MASLD affects up to one in three adults worldwide, and as many as seven in ten people living with obesity or type 2 diabetes. The first licensed drug treatments for MASH are now entering clinical practice, which raises demand for accurate ways to diagnose and monitor the disease that do not depend on an invasive procedure.

Across the two studies, researchers assessed dozens of blood, imaging and elastography-based biomarkers. These included state-of-the-art tests as well as routine ones doctors already use. Each was compared against liver biopsy read by expert pathologists. The researchers describe the data as prospective and independent, drawn from large multinational patient cohorts, and say it gives the most realistic benchmarks yet.

For advanced fibrosis, meaning scarring, and for cirrhosis, the best performers were the SOMAScan proteomic panel, MR elastography, and FibroScan-based tools, including the Agile 3+ score. The ELF and ADAPT blood tests also cleared predefined performance thresholds for detecting cirrhosis. The imaging study added that elastography techniques did well at detecting advanced fibrosis and cirrhosis, with MR elastography outperforming FibroScan-based stiffness measurements.

Active inflammation is harder. For identifying "at-risk MASH," the group most clinical trials target, only the SOMAScan panel met the predefined accuracy threshold. Professor Quentin Anstee, who holds the Ruth & Lionel Jacobson Chair in Personalised Medicine at Newcastle University, is an honorary consultant hepatologist at Newcastle Hospitals NHS Foundation Trust, and is joint senior author of both papers and coordinator of the consortium. He said that for advanced scarring and cirrhosis there are now tools good enough to use with real confidence, while detecting active inflammation remains more challenging, though promising tests are becoming available.

One finding concerns routine care. A simple, inexpensive gamma-GT blood test outperformed the widely used FIB-4 score as a first-line assessment. The results support a streamlined pathway: gamma-GT as the initial screen, then ELF or FibroScan for patients who need further assessment, with advanced imaging kept for specialist care. After further validation, the authors say, health systems could adopt it, giving more patients an accurate diagnosis without a biopsy and directing specialist resources to those who need them.

The biopsy is not going away entirely. Regulators require confirmation of at-risk MASH for enrolment in late-stage trials, so biopsy is likely to remain necessary there for now. SOMAScan's performance suggests it could eventually replace it in that role, and the pathway's further validation is the next step to watch.