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

Takahashi, Yoshihiro; Seko, Yuya; Yamaguchi, Kanji; Takeuchi, Kento; Yano, Kota; Kataoka, Seita; Moriguchi, Michihisa; Itoh, Yoshito

doi:10.1111/jgh.16222

Cited by 7 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is generally in line with a previously reported result: In a retrospective analysis of 75 patients with MASLD complicated by dyslipidemia using the FibroScan‐AST (FAST) score as a measure of treatment response, baseline γ‐GTP emerged as an independent predictor of the response to pemafibrate treatment. 43 These findings suggest that pemafibrate treatment may offer greater efficacy in MASLD patients with higher liver enzyme levels, providing a rationale for selecting pemafibrate in such patients.…”

Section: Discussionmentioning

confidence: 89%

Impact of pemafibrate in patients with metabolic dysfunction‐associated steatotic liver disease complicated by dyslipidemia: A single‐arm prospective study

Ono,

Atsukawa,

Tsubota

et al. 2024

JGH Open

View full text Add to dashboard Cite

Background and AimThis study aimed to clarify the efficacy and safety of 48‐week pemafibrate treatment in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) complicated by dyslipidemia.MethodsA total of 110 patients diagnosed with MASLD complicated by dyslipidemia received pemafibrate at a dose of 0.1 mg twice daily for 48 weeks.ResultsThe participants were 54 males and 37 females, with a median age of 63 (52–71) years. Besides improvement in lipid profile, significant reductions from baseline to 48 weeks of treatment were found in liver‐related enzymes, such as aspartate aminotransferase, alanine aminotransferase (ALT), gamma‐glutamyl transpeptidase, and alkaline phosphatase (P < 0.001 for all). A significant decrease in the homeostasis model assessment‐insulin resistance (HOMA‐IR) was observed in patients with insulin resistance (HOMA‐IR ≥ 2.5) (4.34 at baseline to 3.89 at Week 48, P < 0.05). Moreover, changes in ALT were weakly correlated with those in HOMA‐IR (r = 0.34; p < 0.05). Regarding noninvasive liver fibrosis tests, platelets, Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein, type IV collagen 7s, and the non‐alcoholic fatty liver disease fibrosis score significantly decreased from baseline to Week 48. Most adverse events were Grades 1–2, and no drug‐related Grade 3 or higher adverse events were observed.ConclusionThis study demonstrated that 48‐week pemafibrate administration improved liver‐related enzymes and surrogate marker of liver fibrosis in patients with MASLD. The improvement of insulin resistance by pemafibrate may contribute to the favorable effect on MASLD complicated by dyslipidemia.

show abstract

Section: Discussionmentioning

confidence: 89%

Impact of pemafibrate in patients with metabolic dysfunction‐associated steatotic liver disease complicated by dyslipidemia: A single‐arm prospective study

Ono,

Atsukawa,

Tsubota

et al. 2024

JGH Open

View full text Add to dashboard Cite

show abstract

“… 33 , 34 Recent studies have reported a significant decrease in the FAST score following pemafibrate treatment 16 , 19 , 35 and its correlation with the changes in ALT 16 or GGT levels. 35 In this study, we found a significant reduction in the MAST score following pemafibrate treatment and a correlation between the reduction of the MAST score and the changes in ALT and GGT levels. The reduction of ALT levels indicates an improvement in histological inflammation in patients with biopsy‐proven NASH.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of the effects of pemafibrate on metabolic dysfunction‐associated steatotic liver disease with hypertriglyceridemia using magnetic resonance elastography combined with fibrosis‐4 index and the magnetic resonance imaging‐aspartate aminotransferase score

Ichikawa,

Oba,

Owada

et al. 2023

JGH Open

View full text Add to dashboard Cite

Background and AimIn this retrospective study, we evaluated the effects of pemafibrate treatment in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD) and hypertriglyceridemia using non‐invasive stiffness‐based models, including magnetic resonance elastography (MRE) combined with the fibrosis‐4 (FIB‐4) (MEFIB) index and the magnetic resonance imaging (MRI)‐aspartate aminotransferase (AST) (MAST) score.MethodsIn total, 179 patients with MASLD treated with pemafibrate were enrolled. We evaluated the effects of 48‐week pemafibrate treatment using the MEFIB index, which classifies patients based on the combination of liver stiffness measurement (LSM) on MRE and FIB‐4 and the MAST score, which is calculated based on LSM on MRE, MRI‐proton density fat fraction (MRI‐PDFF), and AST levels.ResultsPemafibrate treatment led to significant reduction in AST, alanine aminotransferase (ALT), and gamma‐glutamyl transferase (GGT) (P = 0.011, <0.001, and <0.001, respectively) and significant improvements in triglyceride and high‐density lipoprotein cholesterol levels (P < 0.001 and <0.001, respectively). The MRI‐PDFF values were not significantly altered. However, a significant decrease in LSM on MRE was detected (P = 0.003). Evaluation of fibrosis using the MEFIB index and MAST score demonstrated significant improvement (P = 0.004 and <0.001, respectively). Changes in the MAST score showed positive correlation with changes in ALT and GGT levels (r = 0.821, P < 0.001, and r = 0.808, P < 0.001, respectively). Additionally, ALT and GGT levels at baseline were significantly associated with improvements in the MAST score (P < 0.001 and <0.001, respectively).ConclusionPemafibrate led to improvements in the MEFIB index and MAST score, as well as liver function. It is a promising therapeutic agent for patients with MASLD and hypertriglyceridemia with the potential to reduce liver‐related events.

show abstract

“…ALP is present in the ducts of the liver, and GGT is located on liver cell membranes ( Inoue et al, 2023 ). The combined elevation of ALP and GGT can indicate obstructive or cholestatic liver disease, where bile is not properly transported from the liver because of an obstruction of the bile duct ( Takahashi et al, 2023 ). GGT is also an indicator of alcohol use ( De Silva et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Liver function indicators and risk of hepatocellular carcinoma: a bidirectional mendelian randomization study

Qin,

Wang,

Yuan

et al. 2024

Front. Genet.

View full text Add to dashboard Cite

Observational studies have shown an association between liver dysfunction and hepatocellular carcinoma (HCC), but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between liver function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; γ-glutamyltransferase, GGT) and HCC. Our two-sample Mendelian randomization (MR) study acquired single nucleotide polymorphisms (SNPs) associated with liver function indicators (ALT, n = 134,182; AST, n = 134,154; GGT, n = 118,309; ALP, n = 105,030) and with HCC (n = 197,611) from publicly available genome-wide association studies (GWAS) of East Asian ancestry in Japan (BioBank Japan, BBJ). Univariable MR analyses were performed to identify whether the genetic evidence of exposure was significantly associated with outcome. Multivariable MR analysis was conducted to estimate the independent effects of exposures on outcome. Univariable MR analysis indicated that the level of ALT, AST, and GGT was the risk factor for HCC incidence. Meanwhile, multivariable MR analysis revealed that AST was an independent risk factor for HCC. The hazard ratio (HR) of the probability of HCC was 3.045 [95% confidence interval (95%CI), 1.697–5.463, p = 0.003] for AST. The results of reverse MR analyses showed that gene-predictive HCC incidence could increase the levels of AST (HR = 1.031, 95%CI: 1.009–1.054, p = 2.52 × 10−4) and ALT (HR = 1.040, 95%CI: 1.019–1.063, p = 0.005). Meanwhile, HCC may be negatively correlated with ALP levels (HR = 0.971, 95%CI: 0.947–0.995, p = 0.018). This study provides evidence to support that genetically predicted higher levels of AST are related to increased risk of HCC, with no strong evidence of a causal effect of genetically predicted ALP, ALP, and GGT on HCC. In addition, genetic predisposition to HCC could influence blood concentration of ALT, AST, and ALP. Thus, this may create a vicious cycle.

show abstract

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

Cited by 7 publications

References 37 publications

Impact of pemafibrate in patients with metabolic dysfunction‐associated steatotic liver disease complicated by dyslipidemia: A single‐arm prospective study

Impact of pemafibrate in patients with metabolic dysfunction‐associated steatotic liver disease complicated by dyslipidemia: A single‐arm prospective study

Evaluation of the effects of pemafibrate on metabolic dysfunction‐associated steatotic liver disease with hypertriglyceridemia using magnetic resonance elastography combined with fibrosis‐4 index and the magnetic resonance imaging‐aspartate aminotransferase score

Liver function indicators and risk of hepatocellular carcinoma: a bidirectional mendelian randomization study

Contact Info

Product

Resources

About