Does firsocostat reduce hepatic de novo lipogenesis in patients with nonalcoholic steatohepatitis?
Elevated hepatic de novo lipogenesis plays a pathophysiological role in NASH and can be reduced by the acetyl-CoA carboxylase inhibitor firsocostat.
>10 days). Furthermore, DNL contribution was determined to be independent of liver stiffness by magnetic resonance imaging but was positively associated with the number of large very low density lipoprotein (VLDL) particles, the size of VLDL, the lipoprotein insulin resistance score, and levels of ApoB100, and trended toward negative associations with the fibrosis markers FIB-4, FibroSure, and APRI. Finally, we found treatment with the acetyl-CoA carboxylase inhibitor firsocostat reduced hepatic DNL at 4 and 12 weeks, using a correction model for residual label that accounts for hepatic triglyceride turnover. Taken together, these data support an important pathophysiological role for elevated hepatic DNL in NASH and demonstrate that response to pharmacological agents targeting DNL can be correlated with pretreatment DNL.
Lawitz et al. (Mon,) studied this question.
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