In:
Canadian Journal of Gastroenterology and Hepatology, Hindawi Limited, Vol. 2022 ( 2022-12-6), p. 1-13
Kurzfassung:
Background and Aims. A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients. Method. Serum allopregnanolone levels were measured in 120 phenotyped PBC patients and 40 age and gender-matched healthy controls. PBC subjects completed the PBC-40 at recruitment. Serum allopregnanolone levels were compared across PBC-40 domains for those with none/mild symptoms versus severe symptoms. Results. There were no overall differences in allopregnanolone levels between healthy controls (median = 0.03 ng/ml (IQR = 0.025)) and PBC patients (0.031 (0.42), p = 0.42 ). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = −0.53, p 〈 0.001 ) but not healthy controls (r (39) = −0.21, p = 0.21 ). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, p = 0.02 ), emotional (u = 1374, p = 0.004 ), and itch (u = 795, p = 0.03 ). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 p = 0.001 ). Conclusion. Elevated serum allopregnanolone is associated with severe cognitive, emotional, and itch symptoms in PBC, in keeping with its known action on GABA-A receptors. Existing novel compounds targeting allopregnanolone could offer new therapies in severely symptomatic PBC, satisfying a significant unmet need.
Materialart:
Online-Ressource
ISSN:
2291-2797
,
2291-2789
DOI:
10.1155/2022/3618090
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2022
ZDB Id:
2762184-4
