Semin Liver Dis 2021; 41(03): 358-367
DOI: 10.1055/s-0041-1730923
Review Article

MRGPRX4 in Cholestatic Pruritus

Huasheng Yu
1   Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Kirk Wangensteen
2   Gastroenterology Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Tong Deng
3   Department of Pathology, Sidney Sussex College, University of Cambridge, Cambridge, United Kingdom
Yulong Li
4   School of Life Sciences, Peking University, Beijing, China
Wenqin Luo
1   Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
› Author Affiliations
Funding W.L. reports grants from NIH, during the conduct of the study.


Pruritus (itch) is a debilitating symptom in liver diseases with cholestasis, which severely affects patients' quality of life. Limited treatment options are available for cholestatic itch, largely due to the incomplete understanding of the underlying molecular mechanisms. Several factors have been proposed as pruritogens for cholestatic itch, such as bile acids, bilirubin, lysophosphatidic acid, and endogenous opioids. Recently, two research groups independently identified Mas-related G protein-coupled receptor X4 (MRGPRX4) as a receptor for bile acids and bilirubin and demonstrated its likely role in cholestatic itch. This discovery not only opens new avenues for understanding the molecular mechanisms in cholestatic itch but provides a promising target for developing novel anti-itch treatments. In this review, we summarize the current theories and knowledge of cholestatic itch, emphasizing MRGPRX4 as a bile acid and bilirubin receptor mediating cholestatic itch in humans. We also discuss some future perspectives in cholestatic itch research.

Publication History

Article published online:
23 June 2021

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