Abstract
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.
Keywords
MRGRPX4 - cholestasis - pruritus
