When considering more advanced NASH, a trial involving patients with advanced fibrosis or cirrhosis (fibrosis stage 3–4), combination therapy with firsocostat (an acetyl-CoA carboxylase inhibitor), and cilofexor (an FXR agonist) resulted in greater improvements in histology and clinically relevant biomarkers versus either agent alone or placebo, although, as with our trial, the histological end point was not met.29 Here, NR1H4 is linked to fibrosis.