Effect of a combination of pemafibrate and a mild low‐carbohydrate diet on obese and non‐obese patients with metabolic‐associated fatty liver disease

Abstract

Background and Aim: Recently, pemafibrate and a low-carbohydrate diet (LCD) have each been reported to improve fatty liver disease. However, it is unclear whether their combination improves fatty liver disease and is equally effective in obese and non-obese patients. Methods: In 38 metabolic-associated fatty liver disease (MAFLD) patients, classified by baseline body mass index (BMI), changes in laboratory values, magnetic resonance elastography (MRE), and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) were studied after 1 year of combined pemafibrate plus mild LCD. Results: The combination treatment resulted in weight loss (P = 0.002), improvement in hepatobiliary enzymes (γ-glutamyl transferase, P = 0.027; aspartate aminotransferase, P < 0.001; alanine transaminase [ALT], P < 0.001), and improvement in liver fibrosis markers (FIB-4 index, P = 0.032; 7 s domain of type IV collagen, P = 0.002; M2BPGi, P < 0.001). Vibration-controlled transient elastography improved from 8.8 to 6.9 kPa (P < 0.001) and MRE improved from 3.1 to 2.8 kPa (P = 0.017) in the liver stiffness. MRI-PDFF improved from 16.6% to 12.3% in liver steatosis (P = 0.007). In patients with a BMI of 25 or higher, improvements of ALT (r = 0.659, P < 0.001) and MRI-PDFF (r = 0.784, P < 0.001) were significantly correlated with weight loss. However, in patients with a BMI below 25, the improvements of ALT or PDFF were not accompanied by weight loss. Conclusions: Combined treatment with pemafibrate and a low-carbohydrate diet resulted in weight loss and improvements in ALT, MRE, and MRI-PDFF in MAFLD patients. Although such improvements were associated with weight loss in obese patients, the improvements were observed irrespective of weight loss in non-obese patients, indicating this combination can be effective both in obese and non-obese MAFLD patients.

A Comparison of Alanine Aminotransferase Normalization between Pemafibrate and Bezafibrate in Patients with Nonalcoholic Fatty Liver Disease

“…This study revealed that pemafibrate significantly increased the ALT normalization rate compared to bezafibrate. Other studies have shown that pemafibrate improves the liver function ( 31 ). Improvement in ALT levels is linked to improvement in hepatic inflammation and steatosis, leading to improvement in liver fibrosis and liver-related complications ( 25 , 32 - 34 ).…”

“…At 3, 6, and 12 months, ALT levels were significantly decreased in both groups (p <0.05). The median (IQR) ALT levels at entry and 3, 6, and 12 months in patients using pemafibrate in the sensitivity analysis of patients with ALT <100 IU/L were 52 (40-64), 29 (25-56), 31 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), and 26 (20-38) IU/L, respectively. Similarly, in patients with bezafibrate, the median (IQR) ALT levels at entry and 3, 6, and 12 months were 66 (61-69), 43 (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52), 41 , and 39 (32-66) IU/L, respectively.…”

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

“…The first study by Shinozaki et al [ 85 ] treated 71 patients for 6 months, finding that lean patients experienced a greater reduction in ALT and serum mac-2 binding protein glycosylation isomer than obese patients. The second study by Suzuki et al [ 86 ] treated 38 patients for 12 months and found a strong association in the decrease of ALT, AST, hepatic steatosis, and fibrosis in both lean and obese patients. Canagliflozin at a dosage of 100 mg once daily was evaluated in 20 patients with T2DM and NAFLD, but due to only one patient being lean, the results were inconclusive in this population[ 87 ].…”

Relieved Depressive State and Glycemic Control in Type 2 Diabetes (T2D) Patient Treated by Imeglimin (Twymeeg)

“…Recently, some novel agents for dyslipidemia have been introduced to clinical practice, such as ezetimibe, pemafibrate and others [15,16]. These agents can contribute more for clinical efficacy by combination treatment with statins [17,18].…”