Cheap gamma-GT blood test beat FIB-4 for liver scarring screening in LITMUS studies

A cheap blood test called gamma-GT beat the screening score most clinics use to flag liver scarring in people with fatty liver disease. That is the headline result from the LITMUS programme, whose two studies were published on October 29 in The Lancet and Nature Medicine. The Lancet paper has not been independently reviewed here. This report relies on press coverage of it, and the paper's own accuracy figures were not available.

What the two studies tested

LITMUS is a European consortium of 53 academic and industry partners, funded through the Innovative Medicines Initiative 2 Joint Undertaking. Its main study assessed blood tests and ultrasound-based liver stiffness readings in more than 1,500 patients. A second paper, in Nature Medicine, tested advanced MRI and elastography in more than 350 patients. Every test was graded against liver biopsy read by expert pathologists.

The target is metabolic dysfunction-associated steatotic liver disease, or MASLD, formerly called NAFLD. The National Institute of Diabetes and Digestive and Kidney Diseases estimates that about 24% of U.S. adults have it, and 1.5% to 6.5% have the inflammatory form, MASH. The newer names are used in the LITMUS coverage.

Where the tests did well

For advanced fibrosis and cirrhosis, three approaches scored highest: the SOMAScan proteomic blood panel, MR elastography, and FibroScan-based measurements including the Agile 3+ score. In the imaging paper, MR elastography outperformed FibroScan stiffness readings. Two blood tests, ELF and ADAPT, cleared the studies' predefined thresholds for cirrhosis.

Professor Quentin Anstee of Newcastle University, an honorary consultant hepatologist at Newcastle Hospitals NHS Foundation Trust and coordinator of the consortium, is joint senior author of both papers. "For advanced liver scarring and cirrhosis, we now have tools good enough to use with real confidence," he said.

The cheap test that outperformed the standard

The surprise sits at the entry point. As a first-line check, gamma-GT, a routine and inexpensive blood measurement, outperformed FIB-4, the score widely used to decide who needs further testing. The authors propose a three-step order. Gamma-GT comes first, then ELF or FibroScan for patients who need a closer look, and advanced imaging only in specialist care. They state that this pathway needs further validation before health systems adopt it.

None of the coverage reported the numbers behind the comparison, such as the area under the curve, sensitivity, or specificity. Without them, the size of the gamma-GT advantage over FIB-4 cannot be judged. A win on one cohort can also shrink in a different population.

Why biopsy is not going away yet

Anstee also said that detecting active liver inflammation "remains more challenging." That matters because the FDA approved the first MASH drug, Rezdiffra (resmetirom), on March 14, 2024, under accelerated approval. Its trial of 888 people enrolled patients only after a biopsy showed NASH-related inflammation with moderate or advanced scarring, and used repeat biopsies at month 12 to measure results.

Regulators still require confirmation of at-risk MASH for late-stage trial enrollment, so biopsy is likely to stay in that role. SOMAScan's performance suggests a blood panel could eventually replace it there. That is a possibility the authors raise, not a finding.

What this changes and what it does not

The practical gain is in triage. If the gamma-GT pathway holds up, fewer patients would need an invasive procedure or a specialist referral just to learn whether scarring is advanced. Nothing in the reported results changes treatment, and none of these tests is described as approved or available through a particular health system.

The evidence is strongest for advanced scarring and cirrhosis, thinner for inflammation, and preliminary for the gamma-GT screening sequence. Both papers come from one consortium, and the press release language was echoed across outlets that appear to draw on the same Newcastle University statement. Independent replication in routine clinics is the next test.