Systematic review: efficacy of therapies for cholestatic pruritus

Abstract

Background: Pruritus is a symptom of several cholestatic liver diseases (CLDs) that can impair health-related quality of life (HRQoL). Despite evidence-based guideline therapy, managing cholestatic pruritus (CP) remains challenging, thus making the need for newer, more effective therapeutic agents more evident. Objective: Our study evaluated the efficacy of existing CP therapies. Design: Systematic review. Data sources: From inception until March 2023, we conducted a comprehensive search of MEDLINE, Cochrane, EMBASE, Scopus, ClinicalTrial.gov, and other sources, including pharmaceutical webpages and conference proceedings published in English that reported on CP interventions. Methods: Two reviewers independently conducted screening and full-text review of articles with extraction conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The methodological quality of studies included in our qualitative synthesis was assessed by using the Cochrane ROBINS-I and ROBINS-II tools for interventional studies and the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The primary outcome assessed in our systematic review was the severity of CP after therapy. Results: Of 3293 screened articles, 92 studies were eligible for inclusion in the qualitative synthesis. Some patients’ HRQoL improved with evidence-based standard therapy. Others, particularly those with severe and refractory CP, often required conversion to or addition of experimental noninvasive (e.g., ondansetron) or extracorporeal liver support to alleviate CP. In addition, studies investigating a newer class drug, the ileal bile acid transporter inhibitor (IBATi), demonstrate its effectiveness in reducing serum bile acid and alleviating CP with sustained improvement noted in patients with the inherited childhood cholestatic disorders – progressive familial intrahepatic cholestasis and Alagille syndrome. Conclusion: Our findings consolidate data on the efficacy of guideline-based approaches and newer therapies for CP. While the initial findings are promising, additional clinical trials will be needed to determine the full extent of IBATi’s efficacy and potential use in treating other common CLDs. These results provide a foundation for future research and highlight the need for continued investigation into the management and treatment of CLDs.

UDCA for Drug-Induced Liver Disease: Clinical and Pathophysiological Basis

“…151 This explains its generalized use in the clinical practice, far beyond the reduced number of hepatopathies where it has been sufficiently validated, and DILI is not the exception. For example, UDCA is often given in DILI cholestatic conditions where pruritus is a common feature, due to its alleged antipruritic effects in other cholestatic hepatopathies, 152 but the hope also exists that the drug aids to improve the natural history of the disease. A case-by-case decision should be therefore often made, and a clear understanding of the multiple hepatoprotective mechanisms of UDCA should help to better support this decision.…”