Thématique :
- Foie
Originalité :
Très original
Solidité :
Très solide
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Pierre-Emmanuel RAUTOU
Coup de coeur :
  2018 Nov;155(5):1463-1473.e6.  
  doi: 10.1053/j.gastro.2018.07.027.  
  GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic FattyLiver Disease.  
  Loomba R, Kayali Z, Noureddin M, Ruane P, Lawitz EJ, Bennett M, Wang L, Harting E, Tarrant JM, McColgan BJ, Chung C, Ray AS, Subramanian GM, Myers RP, Middleton MS, Lai M, Charlton M, Harrison SA  



De novo lipogenesis is increased in livers of patients with nonalcoholic steatohepatitis (NASH). Acetyl-coenzyme carboxylase catalyzes the rate-limiting step in this process. We evaluated the safety and efficacy of GS-0976, an inhibitor of acetyl-coenzyme A carboxylase in liver, in a phase 2 randomized placebo-controlled trial of patients with NASH.


We analyzed data from 126 patients with hepatic steatosis of at least 8%, based on the magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), and liver stiffness of at least 2.5 kPa, based on magnetic resonance elastography measurement or historical biopsy result consistent with NASH and F1-F3 fibrosis. Patients were randomly assigned (2:2:1) to groups given GS-0976 20 mg, GS-0976 5 mg, or placebo daily for 12 weeks, from August 8, 2016 through July 18, 2017. Measures of hepatic steatosis, stiffness, serum markers of fibrosis, and plasma metabolomics were evaluated. The primary aims were to confirm previous findings and evaluate the relation between dose and efficacy.


A relative decrease of at least 30% from baseline in MRI-PDFF (PDFF response) occurred in 48% of patients given GS-0976 20 mg (P = .004 vs placebo), 23% given GS-0976 5 mg (P = .43 vs placebo), and 15% given placebo. Median relative decreases in MRI-PDFF were greater in patients given GS-0976 20 mg (decrease of 29%) than those given placebo (decrease of 8%; P = .002). Changes in magnetic resonance elastography-measured stiffness did not differ among groups, but a dose-dependent decrease in the fibrosis marker tissue inhibitor of metalloproteinase 1 was observed in patients given GS-0976 20 mg. Plasma levels of acylcarnitine species also decreased in patients with a PDFF response given GS-0976 20 mg. GS-0976 was safe, but median relative increases of 11% and 13% in serum levels of triglycerides were observed in patients given GS-0976.


In a randomized placebo-controlled trial of patients with NASH, we found 12-week administration of GS-0976 20 mg decreased hepatic steatosis, selected markers of fibrosis, and liver biochemistry. ID NCT02856555.


Question posée
Quel est l’effet de l’inhibiteur de l’acetyl-coenzyme A carboxylase GS-0976 chez les malades atteints de NASH ?
Question posée
Cette étude de phase 2, prospective, randomisée contrôlée a inclus 126 malades avec NASH et a montré que l’inhibiteur de l’acetyl-coenzyme A carboxylase GS-0976 diminue la stéatose et peut-être la fibrose hépatique.

Si l’effet de l’inhibiteur de l’acetyl-coenzyme A carboxylase GS-0976 sur la stéatose est clair, l’effet sur la fibrose et l’activité hépatique reste à démontrer.