Novel and Emerging Therapies for Cholestatic Liver Diseases

Jordan Goldstein; Cynthia Levy


Liver International. 2018;38(9):1520-1535. 

In This Article


As animal models and human studies continue to elucidate bile acid physiology, their associated nuclear and surface receptors, transporters and role in cholestatic diseases, the emergence of new therapeutic targets for PBC and PSC is rapidly growing. In addition to bile acid derivatives and FXR agonists, drugs targeting a variety of other signalling pathways are under evaluation, with PPAR agonists possibly showing the most promise so far. The BEZURSO trial and additional studies out of Spain showed pronounced biochemical and symptom improvement in bezafibrate-treated patients with PBC, and, likewise, use of seladelpar led to major improvement in liver biochemistries. Smaller studies suggest biochemical benefit of fibrates and FXR agonists in PSC as well. Unfortunately, experimental therapies which show benefit in PBC have not been as effective for PSC; the lack of adequate animal models and biomarkers in PSC precludes well-designed, hypothesis-driven, trial development. Despite this and other challenges in the design and conduct of clinical trials for cholestatic diseases, much progress has been made. Future trials are likely to evaluate combination therapies of drugs with synergistic mechanisms of action to halt disease progression and improve symptom control.