{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T16:13:18Z","timestamp":1794672798946,"version":"4.9.1"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,2,13]],"date-time":"2008-02-13T00:00:00Z","timestamp":1202860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p><jats:bold>Abstract\u2002<\/jats:bold> Fatigue is one of the most common non\u2010specific symptoms associated with several disease states including liver diseases. Recently, it was reported that levels of progesterone metabolites such as allopregnanolone (3\u03b1,5\u03b1\u2010tetrahydroprogesterone; 3\u03b1,5\u03b1\u2010THP) and isopregnanolone (3\u03b2,5\u03b1\u2010THP) were increased in plasma of patients with chronic fatigue syndrome. We hypothesize that THP metabolites might be associated with fatigue commonly observed in chronic liver diseases. We evaluated fatigue scores and plasma levels of five progesterone metabolites in 16 patients with primary biliary cirrhosis (PBC), 12 patients with chronic hepatitis C (CHC) and 11 age\u2010matched controls. The fatigue impact scale (FIS) ratio was significantly increased (<jats:italic>P\u2003<\/jats:italic>&lt;\u20030.01) in patients with PBC and CHC compared to controls. Plasma levels of 3\u03b1,5\u03b1\u2010THP and pregnanolone (3\u03b1,5\u03b2\u2010THP) were significantly increased in PBC and CHC patients. The other progesterone metabolites, i.e. 3\u03b2,5\u03b1\u2010THP, 3\u03b2,5\u03b2\u2010THP and 3\u03b1,5\u03b1\u2010tetrahydrodeoxycorticosterone were either undetectable or detected only in some patients. Plasma levels of 3\u03b1,5\u03b1\u2010THP and 3\u03b1,5\u03b2\u2010THP were found to be significantly higher in patients with fatigue (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05), while those of patients without fatigue were not significantly different from controls. Both 3\u03b1,5\u03b1\u2010THP and 3\u03b1,5\u03b2\u2010THP are positive allosteric modulators of the gamma\u2010aminobutyric acid type A (GABA\u2010A) receptor and readily cross the blood\u2013brain barrier. The present preliminary findings suggest that increased inhibition through GABA\u2010A receptors due to the accumulation of neuroinhibitory steroids may represent an important pathophysiological mechanism of fatigue in chronic liver diseases.<\/jats:p>","DOI":"10.1111\/j.1365-2982.2007.01080.x","type":"journal-article","created":{"date-parts":[[2008,2,13]],"date-time":"2008-02-13T08:38:50Z","timestamp":1202891930000},"page":"671-679","source":"Crossref","is-referenced-by-count":28,"title":["Neuroactive steroids and fatigue severity in patients with primary biliary cirrhosis and hepatitis C"],"prefix":"10.1111","volume":"20","author":[{"given":"S.","family":"Ahboucha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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