TOPLINE:

Several noninvasive tests (NITs) used in patients with metabolic dysfunction-associated steatohepatitis (MASH) treated with semaglutide for 72 weeks showed significant reductions in relevant parameters, with changes evident as early as 28 weeks.

METHODOLOGY:

• Because liver biopsies are not feasible or recommended for monitoring patients with MASH, researchers conducted a retrospective analysis of a phase 2b trial to explore whether NITs could serve as biomarkers for semaglutide response in patients with biopsy-confirmed MASH and liver fibrosis stages 1-3.
• Patients were randomly assigned to receive either semaglutide (0.1, 0.2, or 0.4 mg) or placebo for 72 weeks. A total of 202 patients in the pooled semaglutide group and 66 in the placebo group completed the treatment course.
• Liver biopsies were obtained at baseline and week 72, and serum samples were collected at baseline and weeks 28, 52, and 72.
• The performances of 17 NITs — including tests assessing liver enzyme levels, fibrosis-4 index, liver stiffness measure (LSM), and enhanced liver fibrosis (ELF) — were evaluated over 72 weeks.

TAKEAWAY:

• All NIT scores decreased by a significantly greater amount in the semaglutide group than in the placebo group, with reductions apparent by week 28.
• More semaglutide users were found to be treatment responders, defined as a ≥ 20% change in an NIT (or ≥ 0.5 U for ELF). NIT improvements were linked to increased histologic MASH resolution and reduced fibrosis progression.
• Among patients with baseline LSM ≥ 8 kPa, a greater percentage of those on semaglutide achieved LSM < 8 kPa than those on placebo (55% vs 21%; P = .001). Similarly, among patients with a baseline ELF ≥ 9.8 U, a greater percentage on semaglutide achieved ELF < 9.8 U than those on placebo (50% vs 28%; P = .047).
• Lower baseline readings on fibrosis-related NITs predicted spontaneous improvement at 72 weeks, with the SomaSignal fibrosis test classifying improvement with 74.2% accuracy.

IN PRACTICE:

"NITs may be used for assessing a treatment response in patients with MASH. Further studies should confirm the treatment effect of NITs and evaluate the association of NIT changes to outcomes ," the authors wrote. 

SOURCE:

This study, led by Louise Maymann Nitze, associate director at Novo Nordisk A/S, Søborg, Denmark, was published online in Alimentary Pharmacology & Therapeutics.

LIMITATIONS: 

This exploratory analysis was not corrected for multiple comparisons and may need cautious interpretation. The small and predominantly White study population limited generalizability. Histological sampling and reader variability meant NITs may not perfectly match biopsy findings.

DISCLOSURES:

This study received funding from Novo Nordisk A/S. Five authors reported being employees and shareholders of Novo Nordisk. Several authors reported receiving consulting fees, grants, owning stock, and having other financial ties with multiple pharmaceutical, biotechnology, and healthcare companies, including Novo Nordisk, Gilead, and Roche. One author reported being the co-founder of Illuminatio Medical Technology Limited.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.