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The study aims\u00a0were to evaluate fatigue and its associations in <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> and investigate whether overt autonomic dysfunction contributes to the expression of fatigue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> patients under active follow\u2010up at a regional liver centre were sent disease\u2010 and symptom\u2010assessment tools. Three control groups were utilized; unselected community controls, patients with inflammatory bowel disease (<jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>) without <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content>, and cholestatic controls with primary biliary cirrhosis (<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>). A representative subgroup of <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> patients and normal controls underwent formal autonomic assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Symptom\u2010assessment tools were returned by 40 non\u2010transplanted patients. <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content>\u00a0patients had significantly worse fatigue than population controls (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.005). Fatigue was significant compared to population controls whether or not patients had accompanying <jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>, although was more marked in those with both <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>. In patients with <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">IBD<\/jats:styled-content>, fatigue severity and autonomic symptoms were significantly increased in those with prior significant surgical intervention. Clinically significant autonomic dysfunction was seen in 22.5% of <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> patients, and of those, 78% had significant fatigue. Neurally mediated hypotension was found in 60% of <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> patients compared to 8% in the control group. The <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> group had increased sympathetic activity and reduced parasympathetic activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Fatigue is a significant problem in a minority of <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> patients and appears to be associated with autonomic dysfunction. Fatigued <jats:styled-content style=\"fixed-case\">PSC<\/jats:styled-content> patients should be screened for autonomic dysfunction and targeting such dysfunction represents a potential approach to treatment which warrants further exploration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12709","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T07:51:18Z","timestamp":1414828278000},"page":"1633-1641","source":"Crossref","is-referenced-by-count":33,"title":["Fatigue in primary sclerosing cholangitis is associated with sympathetic over\u2010activity and increased cardiac output"],"prefix":"10.1111","volume":"35","author":[{"given":"Jessica K.","family":"Dyson","sequence":"first","affiliation":[{"name":"The Liver Unit Freeman Hospital Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Elsharkawy","sequence":"additional","affiliation":[{"name":"The Liver Unit University Hospitals Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Lamb","sequence":"additional","affiliation":[{"name":"The Liver Unit Freeman Hospital Newcastle Upon Tyne UK"},{"name":"Institute for Cellular Medicine Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Al\u2010Rifai","sequence":"additional","affiliation":[{"name":"Salford Royal NHS Foundation Trust Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Newton","sequence":"additional","affiliation":[{"name":"UK NIHR Biomedical Research Centre in Ageing Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Jones","sequence":"additional","affiliation":[{"name":"The Liver Unit Freeman Hospital Newcastle Upon Tyne UK"},{"name":"Institute for Cellular Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"UK NIHR Biomedical Research Centre in Ageing Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hudson","sequence":"additional","affiliation":[{"name":"The Liver Unit Freeman Hospital Newcastle Upon Tyne UK"},{"name":"Institute for Cellular Medicine Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.155"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24351"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/egh.10.33"},{"key":"e_1_2_8_5_1","first-page":"55","volume-title":"Primary Sclerosing Cholangitis. 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