{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:38:08Z","timestamp":1789562288833,"version":"build-2803163510"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T00:00:00Z","timestamp":1537574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T00:00:00Z","timestamp":1537574400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue, which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the antimitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B\u2010cell depletion therapy will improve fatigue. In our single\u2010center phase 2 randomized controlled trial, 57 participants aged 18 years or older with PBC and moderate to severe fatigue were randomized to receive two doses of either rituximab (1000 mg) or saline (placebo). The primary outcome measure was fatigue severity assessed using the PBC\u201040 fatigue domain at 3 months. Secondary outcome measures included patient\u2010reported outcomes and immunological and bioenergetics disease parameters. Experimental outcomes included biochemical markers of disease severity. Improvement in fatigue score at 3 months was seen in both arms, with no significant difference (adjusted mean difference \u22120.9 [95% confidence interval \u22124.6 to 3.1]). Little difference was observed in other patient\u2010reported outcomes or physical activity. Significant anaerobic threshold improvement was seen in the rituximab group, only but this was not associated with fatigue improvement. No treatment\u2010emergent serious adverse events were seen. <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic> Rituximab was safe over the 12\u2010month study period but showed no evidence of effectiveness for the treatment of fatigue in PBC. Anaerobic threshold improvement was seen, potentially linking AMA with muscle bioenergetics dysfunction; however, this was not related to improvement in fatigue. Rituximab had some evidence of a beneficial effect on alkaline phosphatase levels in this largely ursodeoxycholic acid (UDCA)\u2013responding, early\u2010disease stage cohort. (H<jats:sc>epatology<\/jats:sc> 2018; 00:000\u2010000).<\/jats:p>","DOI":"10.1002\/hep.30099","type":"journal-article","created":{"date-parts":[[2018,5,23]],"date-time":"2018-05-23T09:01:04Z","timestamp":1527066064000},"page":"1646-1657","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":66,"title":["Rituximab Is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A Phase 2 Randomized Controlled Trial"],"prefix":"10.1097","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7714-5409","authenticated-orcid":false,"given":"Amardeep","family":"Khanna","sequence":"first","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle upon Tyne,United Kingdom"},{"name":"NIHR Biomedical Research Center,Newcastle University,Newcastle upon Tyne,United Kingdom"},{"name":"Freeman Hospital,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Jopson","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle upon Tyne,United Kingdom"},{"name":"NIHR Biomedical Research Center,Newcastle University,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-548X","authenticated-orcid":false,"given":"Denise","family":"Howel","sequence":"additional","affiliation":[{"name":"Institute of Health & Society,Newcastle University,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bryant","sequence":"additional","affiliation":[{"name":"Institute of Health & Society,Newcastle University,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Blamire","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle upon Tyne,United Kingdom"},{"name":"NIHR Biomedical Research Center,Newcastle University,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Newton","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle upon Tyne,United Kingdom"},{"name":"NIHR Biomedical Research Center,Newcastle University,Newcastle upon Tyne,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle upon Tyne,United Kingdom"},{"name":"NIHR Biomedical Research Center,Newcastle University,Newcastle upon Tyne,United 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