Serum levels of IL-31 and autotaxin are independently associated with pruritus severity in patients with primary sclerosing cholangitis
Recommended Citation
Levy C, Pratt D, Lammert C, Gordon SC, Li M, Forman L, Dean R, Yazdanfar M, Patel I, Bordia R, Cosar D, Specht K, Barry F, McLaughlin M, Mukherjee S, Gungabissoon U, Bowlus CL. Serum levels of IL-31 and autotaxin are independently associated with pruritus severity in patients with primary sclerosing cholangitis. J Hepatol 2025; 82:S315.
Document Type
Conference Proceeding
Publication Date
5-1-2025
Publication Title
J Hepatol
Abstract
Background and aims: Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic liver disease with no approved treatment and few effective off-label therapies to reduce the symptom burden. We previously reported that over 1 3 of patients with PSC experience moderate-to-severe pruritus. However, little is known about biomar_kers of pruritus in patients with PSC. The aim of this analysis was to prospectively identify biomarkers of pruritus in PSC. Method: Patients aged 18 and older, diagnosed with PSC and without a liver transplant were enrolled at 7 academic medical centers from July 2021 to March 2024. Itch numeric rating scale (NRS), 5-D Itch, PSC-PRO, and SF-36 were completed and serum collected at the time of enrollment. For the NRS, patients reported their average and worst itch (WI) in the past 24 hours, 7 days, and 6 months. Colitis activity was assessed in patients with inflammatory bowel disease (IBD) by the Simple Clinical Colitis Activity Index (P-SCCA). Total serum bile acids (TSBA), liver biochemistries, IL-31, and autotaxin were mea_sured. Spearman rank correlation, general linear models, and area under the receiver operator curve were used to examine the relationships between the WI in the past 7 days (WI-NRS) and serum biomarkers. Results: A total of 200 patients were enrolled (51% male; mean (SD) age of 44.6 (16.1) years; 71% White, 11% Black African American; 15% cirrhosis). Most patients (77%) had large duct PSC while 4% had small duct PSC and 2% had PSC-AIH. IBD was present in 70% (50% ulcerative colitis 17% Crohn’s disease 3% indeterminate). WI-NRS was reported as moderate or severe (WI-NRS 4–7 or 8–10, respectively) by 48 (24%). Alkaline phosphatase (ALP) (r = 0.26), GGT (r = 0.18), ALT (r = 0.15), AST (r = 0.20), total (r = 0.25) and direct bilirubin (r = 0.26), albumin (r = −0.18), total serum bile acids (r = 0.21), autotaxin (r = 0.28), and IL-31 (r = 0.40) all correlated with WI-NRS (all p-values <0.05). Among patients with IBD, P-SCCA also correlated with WI_NRS (r = 0.41, p < 0.0001). General linear modeling demonstrated that log AST (b = −3.2), log direct bilirubin (b = 1.4), log autotaxin (b = 1.9), and IL-31 (b = 0.6) independently associated with WI-NRS (all p_values <0.05). Among patients with IBD, log autotaxin (b = 4.0, p = 0.0006) and P-SCCA (b = 1.5, P = 0.002), but not IL-31 (b = 0.5, p = 0.15) remained independently associated with WI-NRS. The area under the receiver-operator curve (AUROC) for WI-NRS <4 vs ≥ 4 was 0.68 (0.57– 0.78) for autotaxin and 0.67 (0.56–0.79) for IL-31. Combining autotaxin and IL-31 did not improve the AUROC [0.70 (0.60–0.80)]. Conclusion: Both autotaxin and IL-31 independently associated with pruritus severity in patients with PSC. However, only autotaxin remained an independent predictor of pruritus severity after adjusting for colitis activity in patients with concomitant IBD. This study was supported by GSK (214524)
Volume
82
First Page
S315
