Small Dutch trial links senolytic combination to liver biopsy improvements in fibrotic MASH

A small randomized trial from Amsterdam University Medical Center has reported that an intermittent course of the “senolytic” combination dasatinib plus quercetin was associated with better liver biopsy results in people with fibrotic metabolic dysfunction-associated steatohepatitis (MASH). The trial, published in Nature Metabolism on October 1, 2026, involved only 31 people, and its authors describe the main finding as hypothesis-generating rather than confirmatory.

What the researchers did

Senolytics are drugs designed to clear “senescent” cells, which have stopped dividing and can release inflammatory signals. Cellular senescence is regarded as one of the hallmarks of aging, and the authors note that senescent cells have been linked to inflammation and scarring (fibrosis) in MASH, a progressive form of fatty liver disease.

The team ran a single-center, double-blind, placebo-controlled phase 2 trial (registered as NCT05506488) between July 2023 and February 2026. Thirty-one adults with biopsy-proven fibrotic MASH were randomized to dasatinib (100 mg a day) plus quercetin (1,000 mg a day), or to matching placebo. Treatment was given for three consecutive days a week for three weeks, followed by a four-week break. That seven-week cycle was repeated three times, giving a 21-week study. Liver biopsies were taken at the start and end and scored centrally by three pathologists who did not know which group each sample came from.

Dasatinib is a tyrosine kinase inhibitor approved by the European Medicines Agency; quercetin is a naturally occurring flavonoid. In this trial both were given within a supervised clinical study.

What they found

The primary endpoint was an improvement of at least one fibrosis stage without worsening of MASH. This was reached by 8 of 17 people (47%) in the dasatinib-plus-quercetin group and 1 of 14 (7%) in the placebo group (P = 0.021). The difference was 40 percentage points, but the 95% confidence interval was wide (8.2 to 64.5), and the relative risk of 6.59 had a confidence interval of 0.93 to 46.53.

MASH resolution was seen in 9 of 17 (53%) versus 1 of 14 (7%). According to the abstract, the NAFLD Activity Score fell by 1.43 points (±1.22) in the treated group versus 0.39 (±0.77) with placebo. Not every measure favored the combination: the share of people whose activity score improved (71% versus 50%) did not differ significantly, and one alternative fibrosis score (EPoS) was not significant (P = 0.068). Liver enzyme levels were lower in the treated group, but not by a statistically significant margin.

Single-nucleus RNA sequencing of paired biopsies showed lower activity of gene sets related to senescence and fibrosis in the treated group. The authors checked cancer-related pathways and reported no enrichment after treatment.

Side effects were more common with the combination: 14 of 17 people (82%) reported at least one adverse event, against 6 of 14 (43%) on placebo. Most were mild to moderate, and headache was the most frequent. One person left the study because of gastrointestinal symptoms and fatigue. There was no myelosuppression or QTc prolongation, but platelet counts were lower in the treated group (adjusted difference −50.01 × 10⁹ per liter).

What this means

The result adds to a short list of human studies of senolytics, and the authors say it had not previously been established whether clearing senescent cells changes liver biopsy findings in people with MASH. For the aging-research field, its main value is as a signal that targeting senescent cells may be worth testing in larger trials. It does not show that dasatinib plus quercetin is safe or effective for MASH, and it says nothing about slowing aging in healthy people.

Limits of the evidence

• Size: 31 people were randomized and 27 completed, so the primary result rests on very few “responders”.
• Missing data: four people did not have a follow-up biopsy (three in the treated group, one on placebo) and were counted as non-responders. Under the authors’ most conservative sensitivity analysis, the result was no longer statistically significant (P = 0.068); it held in three of four scenarios.
• Baseline imbalance: type 2 diabetes was more common in the treated group (76.5% versus 35.7%).
• Short follow-up: 21 weeks says little about durability or long-term safety.
• Single center, with participants referred from across the Netherlands.
• Funding and interests: the study was supported by Dutch and US grants, and the authors state that funders had no role in design, analysis or publication. Two authors (T. Tchkonia and J. L. Kirkland) declare a financial interest, including patents held by Mayo Clinic covering senolytic drugs and their uses.
• What we read: the full open-access paper on the Nature Metabolism site. We did not see the supplementary files.

Sources

• Koning M, et al. Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial. Nature Metabolism, October 1, 2026. DOI: 10.1038/s42255-026-01643-4 (also at nature.com)
• Trial registration: ClinicalTrials.gov identifier NCT05506488 (cited in the paper; the registry entry itself was not opened for this article).

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