Navigating the liver landscape: upcoming pharmacotherapies for primary sclerosing cholangitis

Introduction: Primary sclerosing cholangitis (PSC) is a bile duct disorder characterized by ductular reaction, hepatic inflammation, and liver fibrosis. The pathogenesis of PSC is still undefined, and treatment options for patients are limited. Previous clinical trials evaluated drug candidates targeting various cellular functions and pathways, such as bile acid signaling and absorption, gut bacteria and permeability, and lipid metabolisms. However, most of phase III clinical trials for PSC were disappointing, except vancomycin therapy, and there are still no established medications for PSC with efficacy and safety confirmed by phase IV clinical trials.

Areas covered: This review summarizes the currently ongoing or completed clinical studies for PSC, which are phase II or further, and discusses therapeutic targets and strategies, limitations, and future directions and possibilities of PSC treatments. A literature search was conducted in PubMed and ClinicalTrials.gov utilizing the combination of the searched term 'primary sclerosing cholangitis' with Other keywords, such as 'clinical trials,' 'antibiotics,' or drug names. Clinical trials at phase II or further were included for consideration.

Expert opinion: Only vancomycin demonstrated promising therapeutic effects in the phase III clinical trial. Other drug candidates showed futility or inconsistent results, and the search for novel PSC treatments is still ongoing.