Histological and molecular responses to pemafibrate in MASLD with hypertriglyceridemia: the CLARITY study

Pemafibrate (0.2 mg/day) in 33 patients with MASLD and hypertriglyceridemia improved fibrosis stage in 16 (48.5%) over 52 weeks, with NAS also decreasing significantly.

• Why it matters: Histological and cell-type-specific molecular effects of pemafibrate in MASLD with hypertriglyceridemia are not well characterized, limiting mechanistic interpretation of treatment responses.
• What they did: In the prospective single-arm CLARITY study, paired liver biopsies at baseline and 52 weeks were combined with single-nucleus RNA sequencing, paired hepatic qPCR, and circulating proteomics.
• The result: Hepatocyte PPAR/fatty acid oxidation transcriptional scores increased, fibrogenic extracellular matrix and inflammatory programmes fell, and circulating FGF21 rose while DCN, IL1B, and CXCL8 fell.

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