Histopathological changes in two patients with hypertriglyceridemia and metabolic dysfunction-associated steatotic...

This study investigated histological liver-tissue changes before and after 1 year of pemafibrate treatment in two women with metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertriglyceridemia who were refractory to ≥ 6 months of lifestyle intervention. The patients underwent paired liver biopsies before and after receiving pemafibrate (0.2 mg, once daily) for 52 weeks. Improvements in the non-alcoholic fatty liver disease activity score and fibrosis stage were examined. In Case 1, pre-treatment liver biopsy revealed 90% steatosis, ballooning, lobular inflammation, and fibrosis (Brunt grade 2, stage 3). Post-treatment, steatosis decreased to 50%, ballooning and inflammation resolved, and fibrosis improved (grade 1, stage 2). In Case 2, pre-treatment liver biopsy showed 70% steatosis, mild lobular inflammation, and fibrosis (grade, 1, stage 3). Post-treatment, steatosis increased to 90%, inflammation resolved, and fibrosis improved (grade 1, stage 1). The fibrosis-4 index improved in both cases; however, shear wave elastography showed no improvement. Pemafibrate may exert antifibrotic and anti-inflammatory effects in MASLD regardless of steatosis trends and that histological assessment remains crucial, especially when non-invasive markers provide inconsistent results. This is the first report to confirm histopathological improvement with pemafibrate via serial liver biopsy, offering important insights into its therapeutic potential for MASLD with dyslipidemia.