IL-31 serum levels correlate with pruritus and may be a useful biomarker for studies investigating therapies in patients with cholestatic diseases such as Alagille syndrome (ALGS), according to a new study published in Hepatology.

Levels of IL-31 were found to be elevated in patients with other cholestatic diseases including primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) compared to healthy volunteers. The IL-31 levels were positively correlated with the visual analog scale for pruritus and the 5-D itch scale.

The study also found that IL-31 levels increased in patients with nonalcoholic steatohepatitis (NASH) who were receiving treatment with the farnesoid X receptor agonist, cilofexor, in a dose-dependent fashion. Cilofexor did not alter serum IL-31 levels in patients with PSC and PBC, however.

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In the overall group of patients with PSC, PBC, and NASH, serum IL-31 levels correlated with serum bile acid levels (P <.001) but not with other liver injury and fibrosis biomarkers such as alanine aminotransferase, aspartate aminotransferase, or Enhanced Liver Fibrosis score. This suggests that IL-31 is primarily related to the level of cholestasis rather than liver injury, the authors said.

Through in situ hybridization of commercially-procured cells from patients with NASH and PSC, cells staining positive for IL-31 (IL-31+) were found in liver cells. These liver cells included both nonparenchymal cells and hepatocytes. IL-31+ cells were almost absent in samples procured from healthy volunteers.

“IL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with [famesoid X receptor] agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression,” the authors concluded. “These findings have therapeutic implications for patients with liver disease and pruritus.”

The data in the study was obtained from 5 clinical trials investigating the use of cilofexor including a phase 1 study (NCT02654002), and 4 placebo-controlled phase 2 studies in patients with noncirrhotic NASH (NCT02854605), cirrhotic NASH (NCT02781584), noncirrhotic PSC (NCT02943460), and non-cirrhotic PBC (NCT02943447). A total of 343 participants were included in the study across all 5 trials.


Xu J, Wang Y, Khoshdeli M, et al. IL-31 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is FXR responsive in NASH. Hepatology. Published online June 10, 2022. doi:10.1002/hep.32599