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• W4311652188 abstract "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), <math xmlns=http://www.w3.org/1998/Math/MathML id=M1> <mi>p</mi> <mo>=</mo> <mn>0.42</mn> </math> ). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = −0.53, <math xmlns=http://www.w3.org/1998/Math/MathML id=M2> <mi>p</mi> <mo><</mo> <mn>0.001</mn> </math> ) but not healthy controls (r (39) = −0.21, <math xmlns=http://www.w3.org/1998/Math/MathML id=M3> <mi>p</mi> <mo>=</mo> <mn>0.21</mn> </math> ). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, <math xmlns=http://www.w3.org/1998/Math/MathML id=M4> <mi>p</mi> <mo>=</mo> <mn>0.02</mn> </math> ), emotional (u = 1374, <math xmlns=http://www.w3.org/1998/Math/MathML id=M5> <mi>p</mi> <mo>=</mo> <mn>0.004</mn> </math> ), and itch (u = 795, <math xmlns=http://www.w3.org/1998/Math/MathML id=M6> <mi>p</mi> <mo>=</mo> <mn>0.03</mn> </math> ). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 <math xmlns=http://www.w3.org/1998/Math/MathML id=M7> <mi>p</mi> <mo>=</mo> <mn>0.001</mn> </math> ). 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." @default.
• W4311652188 created "2022-12-27" @default.
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• W4311652188 date "2022-12-06" @default.
• W4311652188 modified "2023-10-17" @default.
• W4311652188 title "Neurosteroid Activation of GABA-A Receptors: A Potential Treatment Target for Symptoms in Primary Biliary Cholangitis?" @default.
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• W4311652188 doi "https://doi.org/10.1155/2022/3618090" @default.
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