Serum Bile Acid Elevation is an Independently Associated With Pruritus in Patients With At-risk Metabolic Dysfunction-associated Steatotic Liver Disease

Elevated serum bile acids are associated with pruritus in cholestatic liver diseases. We assessed the association of serum bile acids and other putative biomarkers of cholestatic pruritus (autotaxin and interleukin-31 (IL-31) with pruritus in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

We used serum from patients with MASLD and metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis B, viral hepatitis C, and healthy blood donors to measure the levels of bile acids, autotaxin, and IL-31. Clinically significant pruritus was defined from the Chronic Liver Disease Questionnaire.

Six hundred fifty-one subjects were included [MASLD (N = 497, 88 MASH), viral hepatitis B and C (VH, N = 98), healthy controls (N = 56)]. Post hoc definitions of high biomarker levels associated with the presence of clinically significant pruritus were as follows: high bile acids ≥5.9 μmol/L, high autotaxin ≥220 ng/mL, and high IL-31 ≥ 25 pg/mL. The VH patients had the highest bile acids levels and lowest levels were in healthy controls (P < 0.0001). The highest autotaxin levels were seen in hepatitis C, while the highest IL-31 levels in MASH. MASH patients had higher levels of all three biomarkers than non-MASH-MASLD. Also, at-risk MASLD or MASLD with advanced fibrosis (AF) had higher bile acids and autotaxin (all P < 0.01) but not IL-31 (P > 0.05). MASLD patients with high bile acids had more pruritus (all MASLD: 25% vs. 17%; MASH 30% vs. 13%; at-risk MASLD: 33% vs. 12%; AF: 41% vs. 8%). In multivariable logistic regressions, having high bile acids was an independent predictor of pruritus in at-risk MASLD [odds ratio (OR) (95% CI) = 4.4 (1.6-12.1)] and MASLD with advanced fibrosis [OR = 7.5 (2.0-29.0)]; but not autotaxin or IL-31 (all P > 0.05).

High serum bile acid level is independently associated with pruritus in at-risk MASLD.