Cholestatic liver diseases: An era of emerging therapies

Area of Science:

• Hepatology and Gastroenterology
• Molecular Pharmacology
• Drug Discovery

Background:

• Cholestasis, a liver disease, involves impaired bile secretion, with ursodeoxycholic acid (UDCA) as the current standard therapy.
• Recent advancements have improved understanding of bile secretion mechanisms and cholestatic disease perturbations.
• Many patients do not respond favorably to UDCA, necessitating novel therapeutic strategies.

Purpose of the Study:

• To review recent and future promising therapeutic agents for cholestatic liver disorders.
• To discuss the potential molecular mechanisms of these novel anti-cholestatic agents.
• To highlight new drug targets beyond UDCA for cholestasis treatment.

Main Methods:

• Literature review of recent scientific publications on cholestasis and therapeutic agents.
• Analysis of molecular mechanisms underlying novel treatment targets.
• Discussion of emerging therapeutic options and their clinical potential.

Main Results:

• Identification of novel therapeutic targets including nuclear receptors (e.g., farnesoid X receptor) and G protein-coupled receptors (e.g., transmembrane G coupled receptor 5).
• Highlighting the roles of fibroblast growth factor-19 and enterohepatic bile acid transporters as potential drug targets.
• Introduction of norursodeoxycholic acid (norUDCA) as a promising therapeutic agent.

Conclusions:

• The field of cholestasis has seen significant expansion, leading to novel therapeutic options.
• Emerging treatments target key molecular pathways involved in bile acid homeostasis.
• These advancements offer potential new treatments for patients with cholestatic liver diseases unresponsive to current therapies.