Aim: Dyslipidemia (DL) is commonly associated with non-alcoholic fatty liver disease (NAFLD). Pemafibrate, a selective peroxisome proliferator activated receptor α modulator (SPPARMα), has been shown to improve liver function among patients with DL. The aim of this single-arm prospective study is to evaluate the efficacy of pemafibrate in NAFLD patients with DL. Methods: Twenty NAFLD patients with DL who received pemafibrate (0.1 mg) twice a day for 12 weeks were prospectively enrolled in this study. The primary end-point was change in serum alanine aminotransferase (ALT) levels from baseline to week 12. Results: Serum ALT levels decreased from 75.1 IU/L at baseline to 43.6 IU/L at week 12 (P=0.001). Significant improvements in triglyceride, high-density lipoprotein cholesterol, total fatty acid, saturated fatty acid (SFA), and unsaturated fatty acid were also noted. The serum level of remnant-like protein cholesterol, SFA, and polyunsaturated / saturated fatty acid ratio (PUFA / SFA ratio) at baseline were correlated with change in ALT level (r=À0.53, r=À0.57, and r=0.46, respectively). Change in PUFA and change in PUFA / SFA ratio were negatively correlated with change in ALT level (r=À0.49 and r=À0.53). No hepatic or renal adverse events were reported. Conclusions: Selective peroxisome proliferator activated receptor α could be a promising novel agent for treatment of NAFLD patients with DL by regulating fatty acid composition. A further long-term large-scale trial is warranted to confirm the efficacy of SPPARMα on NAFLD with DL.

Background & AimsPNPLA3 rs738409 has been associated with increased risks of fibrosis in patients with non‐alcoholic fatty liver disease (NAFLD). Recently, carriage of the rs6834314 G allele, which is in high linkage with rs72613567 of 17‐beta‐hydroxysteroid dehydrogenase 13 (HSD17B13), was reported to be associated with a reduced risk of liver injury in NAFLD patients. We estimated the impact of these genetic variants on hepatic fibrosis in Japanese patients with NAFLD.MethodsWe analysed the associations of these genetic variants with liver histology in 290 Japanese patients with biopsy‐proven NAFLD diagnosed during 2002‐2019. During follow‐up, 14 patients (4.8%) developed hepatocellular carcinoma.ResultsPrevalences of the PNPLA3 rs738409 genotypes were 0.17 for CC, 0.41 for CG, 0.42 for GG, and those for HSD17B13 rs6834314 were 0.54 for AA, 0.39 for AG and 0.07 for GG. There was no significant interaction between the PNPLA3 and HSD17B13 genotypes. Prevalences of advanced fibrosis according to PNPLA3/HSD17B13 genotypes were 0.16 for CC,CG/AG,GG, 0.20 for CC,CG/AA, 0.30 for GG/AG,GG and 0.37 for GG/AA. Multivariate analysis identified PNPLA3 GG as a predictor of advanced fibrosis (stage 3/4) in carriers of HSD17B13 AA (odds ratio 2.4, P = .041), but not HSD17B13 AG/GG (P = .776). The HSD17B13 genotype G was significantly associated with lower prevalences of severe inflammation and ballooning and tended to be associated with a higher prevalence of advanced steatosis.ConclusionsIn Japanese patients with NAFLD, carriage of the HSD17B13 rs6834314 G allele attenuated the effect of the PNPLA3 rs738409 GG genotype on advanced hepatic fibrosis.

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Background Sarcopenia is diagnosed with the skeletal muscle index (SMI) or the sarcopenia index (SI). We previously reported that the ratio of skeletal muscle mass to body fat mass (SF ratio) was a novel index of sarcopenia in patients with non‐alcoholic fatty liver disease (NAFLD). The aim of this retrospective study was to evaluate sarcopenia with these indices in patients with NAFLD. Methods One hundred and fifty‐six consecutive patients with biopsy‐proven NAFLD and alanine aminotransferase (ALT) >40 IU/L were enrolled. Liver function and body composition were evaluated in 121 patients after 12 months. We evaluated the relationship between histological findings, changes in liver function, and the SMI, SI, and SF ratio. Results Of the 156 patients enrolled, 13.5% and 26.3% were diagnosed with sarcopenia with the SMI and SI. In patients with hepatic fibrosis stage <2, the SI and the SF ratio were significantly greater than in patients with fibrosis stage ≥2. There was no difference in SMI between groups. In the cohort assessed at baseline and 12 months later, transaminase activity and SMI decreased significantly, and the SF ratio increased over time. A multivariate analysis revealed the presence of the PNPLA3 G allele and an increase in SF ratio (odds ratio, 7.406) as predictive factors of ALT reduction >30% from baseline. Conclusions Due to the high prevalence of obesity, we should consider both skeletal muscle mass and body fat mass in the diagnosis and treatment of NAFLD. The SF ratio could be a useful index in sarcopenic NAFLD.

Background: weight loss as a result of lifestyle intervention is effective when treating non-alcoholic fatty liver disease (NAFLD). We estimated the effects of PNPLA3 rs738409 and HSD17B13 rs6834314 variants in response to diet therapy in Japanese patients with NAFLD. Methods: we analyzed the correlation between the change in liver stiffness and change in body weight in 140 patients administered diet therapy for 1-year, according to PNPLA3 and HSD17B13 genotypes. Results: the bodyweight (BW) reduction rate was greater in patients with the PNPLA3 genotype CC than CG and GG (p = 0.035). Change in liver stiffness measurement (LSM) was significantly associated with a change in BW in PNPLA3 CG/GG (r = 0.279/0.381), but not in PNPLA3 CC (p = 0.187). Change in LSM was correlated with change in BW only in patients with HSD17B13 AG/GG (r = 0.425), but not the AA genotype (p = 0.069). A multivariate analysis identified that a change in LSM was correlated with a change in BW in carriers of HSD17B13 AG/GG (B = 3.043, p = 0.032), but not HSD17B13 AA. The change in LSM of patients with a BW reduction of more than 7% (0.50) was significantly greater than that of patients with a BW reduction of less than 7% (0.83) (p = 0.038). Conclusions: in Japanese patients with NAFLD, HSD17B13 rs6834314 polymorphism is associated with the change in LSM by lifestyle intervention. The approach, including genetic assessments, may contribute to the establishment of appropriate therapeutic strategies to treat NAFLD.