A 30% fall in liver stiffness detects fibrosis regression in MASH about two-thirds of the time

Design

prospective paired-biopsy study nested in a randomised phase 2b placebo-controlled trial, with a separate external validation cohort

Population

160 adults with biopsy-proven MASH and stage 2-3 fibrosis (64% female, median age 56, median BMI 36.5); validation cohort of 48 from the US and Singapore

Primary outcome

fibrosis regression without worsening MASH, detected by a 30% or greater relative decline in liver stiffness

Effect

AUC 0.68 (95% CI 0.58-0.77), validation AUC 0.62 (0.48-0.76); adjusted OR for regression 4.23 (1.79-10.38; p = 0.001)

AASLD guidance holds that a decline in liver stiffness on vibration-controlled transient elastography can serve as a non-invasive endpoint for treatment response in metabolic dysfunction-associated steatohepatitis. This study tested that directly, in 160 adults with biopsy-proven MASH and stage 2-3 fibrosis enrolled in a phase 2b pegozafermin trial, all of whom had paired elastography and liver biopsy at two time points.

A 30% or greater relative decline in liver stiffness detected fibrosis regression without worsening MASH with an area under the curve of 0.68. In a separate validation cohort of 48 patients from the United States and Singapore, it was 0.62. The measure was independently associated with regression after adjustment, with an odds ratio of 4.23.

Those two results say different things and both matter. The association is real — a patient whose stiffness falls by 30% is about four times more likely to have regressed — but the discrimination is modest, which is the practical claim. An AUC near 0.65 will misclassify a substantial minority in both directions.

The authors' conclusion is unusually direct for a paper validating a guideline recommendation: better biomarkers of treatment response are required. Where the decision is a trial endpoint or a costly therapy continuation, a measure this imprecise should not stand alone.

• Read a 30% stiffness decline as supportive evidence of response, not as confirmation of fibrosis regression
• Use the same machine, probe and operator where possible; serial comparisons are only as good as their consistency
• Ensure the patient is fasted and account for hepatic congestion and inflammation, both of which raise stiffness independently of fibrosis
• Where a treatment decision turns on whether fibrosis has regressed, consider what else is available before relying on elastography alone
• Record the absolute values, not only the percentage change

The statistics, in plain English

An area under the curve of 0.68 means that if you picked one patient who regressed and one who did not, the test would rank them correctly about 68% of the time — where 50% is a coin toss and 80% is usually considered the minimum for a clinically useful discriminator. The confidence interval of 0.58 to 0.77 comes close to that coin toss at its lower end. The validation cohort's 0.62 (0.48-0.76) crosses 0.5 entirely, meaning that in that smaller sample the test could not be distinguished from chance. The odds ratio of 4.23 and the AUC measure different things: the first says the association is strong, the second says the test still misclassifies too many individuals.

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