Objectives: The exact etiology of pruritus in chronic cholestasis is unknown. Pruritus
intensity does not correlate with common biochemical indices and there is a lack of
biomarkers guiding diagnosis and treatment. We explored profiles of bile acids (BA)
and muricholic acids (MCA) as well as autotaxin (ATX) antigen levels as potential
circulating biomarkers of pruritus in pediatric patients. Methods: In 27 pediatric
cholestatic patients [autoimmune sclerosing cholangitis (ASC) n = 20 (with pruritus
n = 6, without pruritus n = 14); progressive familial intrahepatic cholestasis (PFIC)
n = 7 (with pruritus n = 5, without pruritus n = 2)] and 23 age-matched controls pruritus
was assessed by a visual analog scale of pruritus (PVAS). We obtained profiles of
serum human BA including MCA using a mass-spectrometry assay and ATX antigen levels
with a commercial ELISA. Results: PFIC and ASC patients exhibited significantly higher
BA-, and MCA levels, than healthy controls, but only PFIC patients showed elevated
ATX antigen levels higher [median: 1,650 ng/ml, interquartile rang (IQR): 776.9-3,742]
compared to controls (median: 315.9 ng/ml, IQR: 251.1-417.2; PFIC p = 0.0003). ASC
patients with pruritus showed only a minor increase in total BA (tBA) levels (median:
76.5 mu mol/L, IQR: 54.7-205), but strikingly higher T-conjugated BA (median: 16.4
mu mol/L, IQR: 8.9-41.4) and total MCA (tMCA) (median: 1.15 mu mol/L, IQR: 0.77-2.44)
levels compared to ASC patients without pruritus (tBA median: 24.3 mu mol/L, IQR:
16.2-80.8; p < 0.0408; T-conjugated BA median: 1.3 mu mol/L, IQR: 0.8-4.9; p = 0.0023;
tMCA median: 0.30 mu mol/L, IQR: 0.13-0.64, p = 0.0033). BA/MCA profiles distinctly
differed depending on presence/absence of pruritus. Different from PFIC patients,
ATX antigen levels were not significantly elevated in ASC patients with (median: 665.8
ng/ml, IQR: 357.8-1,203) and without pruritus (median: 391.0 ng/ml, IQR: 283.2-485.6).
In ASC patients, tBA, tMCA, and ATX antigen levels did not correlate with pruritus
severity. Conclusion: Despite the same underlying disease, pediatric ASC patients
with pruritus exhibit significantly altered BA profiles and MCA levels compared to
ASC patients without pruritus. ATX antigen levels seem to have little diagnostic or
prognostic meaning in ASC patients. An increased ATX activity alone seems not to be
causal for pruritus genesis in ASC patients.
