Abstract / Summary
Background: Pemafibrate, a selective peroxisome proliferator-activated receptor-α (PPARα) modulator, improves liver stiffness and biochemistry in metabolic dysfunction-associated steatotic liver disease (MASLD). The longitudinal responses of serum albumin and butyrylcholinesterase during pemafibrate treatment remain incompletely characterized. We performed an exploratory post hoc analysis to characterize the effects of pemafibrate on these biomarkers in patients with non-cirrhotic MASLD. Methods: In this exploratory post hoc analysis of the randomized PEMA-FL trial, 118 patients with non-cirrhotic MASLD received pemafibrate (0.4 mg/day) or placebo for 72 weeks. Longitudinal changes in serum albumin and butyrylcholinesterase were evaluated. Between-group differences were estimated using ANCOVA, with MMRM performed as a sensitivity analysis. Results: Serum albumin and butyrylcholinesterase remained largely unchanged in the placebo group. In contrast, treatment was associated with a sustained increase in serum albumin and a sustained decrease in serum butyrylcholinesterase from week 4 through week 72. At week 72, the adjusted between-group difference in serum albumin was 0.18 g/dL (95% confidence interval [CI], 0.11 to 0.24). The adjusted between-group difference in serum butyrylcholinesterase was −33.5 U/L (95% CI, −45.2 to −21.7). Findings from the MMRM sensitivity analysis were consistent with those of the primary ANCOVA analyses. Conclusions: In this exploratory post hoc analysis, pemafibrate treatment was associated with a sustained increase in serum albumin and a sustained decrease in butyrylcholinesterase activity in patients with non-cirrhotic MASLD. These biomarkers should be interpreted individually because the mechanisms and clinical significance of their differing responses remain uncertain. ClinicalTrials.gov: NCT03350165; registered on 20 November 2017.