Pemafibrate therapy for non-alcoholic fatty liver disease is more effective in lean patients than obese patients

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with an increasing incidence. Pemafibrate is a novel selective peroxisome proliferator-activated receptor-a (PPAR-a) modulator which is expected to improve NAFLD. The aim of this study is to identify predictors of improvement of hepatic inflammation and fibrosis after pemafibrate therapy in patients with NAFLD.

Seventy-one non-diabetic patients with NAFLD treated with pemafibrate for more than six months were included in this retrospective review. Hepatic inflammation and fibrosis were evaluated by alanine aminotransferase (ALT) and Mac-2 binding protein glycosylation isomer (M2BPGi) levels, respectively.

During six months of pemafibrate therapy, significant improvements were observed in ALT and M2BPGi levels regardless of the body mass index (BMI) compared to baseline. Lean NAFLD was identified as a significant positive predictor for > 50% reduction of ALT showing reduced hepatic inflammation. Subsequent multivariate analysis confirmed this result. Reduction of ALT in the lean NAFLD group (BMI < 25) was significantly greater than in the obese NAFLD group (BMI > 30) (p = 0.034). Lean NAFLD and age > 50 years were identified as significant positive predictors for > 20% reduction of M2BPGi showing reduced hepatic fibrosis. Subsequent multivariate analysis confirmed these results. Reduction of M2BPGi in the lean NAFLD group was significantly greater than in the obese NAFLD group (p = 0.022).

Pemafibrate therapy improves markers of hepatic inflammation and fibrosis regardless of BMI. Patients with lean NAFLD have a greater response to pemafibrate therapy compared to those with obese NAFLD.