Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH.

BACKGROUND AND AIMS: The American Association for the Study of Liver Diseases (AASLD) recommends that a decline in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) can be used as a non-invasive endpoint for treatment response in metabolic dysfunction-associated steatohepatitis (MASH), but there are limited data supporting this statement. We examined the association between a ≥30% relative decline in LSM and fibrosis regression. APPROACH AND RESULTS: This prospective study included 160 adults (64% female) with biopsy-proven MASH and stage 2-3 fibrosis from a randomized, phase 2b, multicenter, placebo-controlled trial of the fibroblast growth factor 21 analog pegozafermin. All participants underwent contemporaneous VCTE assessments and liver biopsy at two time-points. The primary endpoint was fibrosis regression without worsening MASH. The median (IQR) age and body mass index of participants were 56.0 (49.0-62.0) years and 36.5 (32.2-40.4) kg/m². The area under the receiver operating curve (AUC) of a ≥30% relative decline in LSM by VCTE for detecting fibrosis regression was 0.68 (95% CI 0.58-0.77). In multivariable analyses adjusted for age, sex, type 2 diabetes, BMI, and ethnicity, a ≥30% relative decline in LSM was independently associated with fibrosis regression (adjusted OR 4.23, 95% CI 1.79-10.38, p=0.001). In a distinct validation cohort (n=48) from U.S. and Singapore, a ≥30% decline in LSM for detecting fibrosis regression yielded an AUC of 0.62 (95% CI 0.48-0.76). CONCLUSION: A ≥30% relative decline in LSM by VCTE had modest accuracy to detect fibrosis regression without worsening MASH. More effective biomarkers for treatment response are required.