Gamma-glutamyl transferase predicts pemafibrate treatment response in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Pemafibrate, a selective peroxisome proliferator activated receptor α modulator, has been shown to improve liver function among nonalcoholic fatty liver disease (NAFLD) patients with dyslipidemia. The aim of this retrospective study is to identify predictors of pemafibrate efficacy in NAFLD patients. METHODS: A total of 75 NAFLD patients with dyslipidemia who received pemafibrate twice per day for 48 weeks were enrolled in this study. We used the FibroScan-aspartate aminotransferase (FAST) score as a benchmark for treatment efficacy. RESULTS: Median FAST score significantly decreased from 0.96 at baseline to 0.93 at week 48 (P < 0.001). Significant improvements in levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and triglycerides were also noted. The serum level of GGT at baseline was correlated with change in FAST score (r = -0.22, P = 0.049). Changes in AST, ALT, and GGT were positively correlated with change in FAST score (r = 0.71, r = 0.61, and r = 0.38). Multivariate analyses identified age and GGT level at baseline as significantly associated with improvement of FAST score by pemafibrate therapy (odds ratio 1.11, 1.02, respectively). Patients over 50 years of age and with a GGT of 90 IU/L or higher showed significantly greater improvement in the FAST score than other groups. CONCLUSIONS: Pemafibrate improves the FAST score of NAFLD patients with complicating dyslipidemia, especially in older patients with high GGT level. GGT is useful as an indicator of optimal treatment choice for NAFLD patients with dyslipidemia.

The additive effect of genetic and metabolic factors in the pathogenesis of nonalcoholic fatty liver disease.

Both genetic and metabolic factors influence the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to evaluate the impact of these factors at each stage of disease. We analysed the impact of obesity, diabetes mellitus and genetic risk factors (alleles of PNPLA3 or HSD17B13) on nonalcoholic steatohepatitis (NASH), significant fibrosis (stage ≥ 2) and advanced fibrosis (stage ≥ 3) in 346 patients. Genetic high risk was defined as having at least 2 risk alleles. The median age was 59 years, median body mass index was 27.1 kg/m2, and 46.8% had diabetes mellitus. Obesity was a risk factor for NASH, significant fibrosis, and advanced fibrosis. Diabetes mellitus increased the risk of NASH. Genetic risk increased the risk of significant and advanced fibrosis. Odds ratios for NASH, significant fibrosis and advanced fibrosis increased with the number of genetic and metabolic risk factors. The patients with both metabolic and genetic risks had an odds ratio of 12.30 for NASH, 5.50 for significant fibrosis, and 6.25 for advanced fibrosis. Factors strongly impact on the pathology of NAFLD differed according to the fibrosis stages. Synergistic effects were observed between genetic and metabolic factors at all stages.