title: Efficacy and safety of ursodeoxycholic acid composite on fatigued patients with elevated liver function and/or fatty liver: a multi-centre, randomised, double-blinded, placebo-controlled trial.
abstract: OBJECTIVE
  The aim of this study was to assess the effects of ursodeoxycholic acid composite (URSA-S) on fatigue in patients with elevated liver function tests and/or fatty liver disease.
  
  
  METHODS
  In this multi-centre randomised double-blinded placebo-controlled trial, 168 adults who were diagnosed with fatigue based on our criteria and had elevated liver function tests (but not > 5 times the normal level) and/or fatty liver on ultrasonography, were randomised to either the placebo or URSA-S administration group. The rate of improvement of checklist individual strength (CIS) using a cut-off of 76 points at the end of the study (8 weeks), the change in fatigue scale [CIS score and visual analogue scale (VAS)] were evaluated. The adverse effects of URSA-S were also recorded.
  
  
  RESULTS
  The rate of CIS improvement at the end-point was 79.76% and 45.68% in the therapy and placebo groups, respectively (p < 0.05). The fatigue recovery rate of the CIS score and VAS were higher in the therapy (-25.44 ± 18.57, -27.84 ± 2.70) than in the placebo group (-16.59 ± 17.29, -19.46 ± 2.81) (p < 0.05). The difference in fatigue recovery rate between the therapy and placebo groups was significant after 8 weeks. When analysed separately in patients with abnormal liver function tests and fatty liver disease, the fatigue recovery rate of the CIS score and VAS at 8 weeks was higher in the therapy than in the placebo group (p < 0.05). The frequency of adverse events in the therapy group was not significantly higher than that in the placebo group.
  
  
  CONCLUSIONS
  URSA-S is effective for alleviating fatigue in patients with liver dysfunction and/or fatty liver. The adverse effects of URSA-S are not significant. This study is registered at https://clinicaltrials.gov/ct2/show/NCT02415777.
authors.affiliation: Department of Family Medicine, SMG-SNU Boramae Hospital, School of Medicine, Seoul National University, Seoul, Korea.
authors.forename: B
authors.initials: B
authors.lastname: Oh
authors.affiliation: Department of Family Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: W S
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Family Practice and Community Health, Ajou University Hospital, School of Medicine, Ajou University, Suwon, Korea.
authors.forename: S B
authors.initials: SB
authors.lastname: Park
authors.affiliation: Department of Family Medicine, Seoul National University Hospital, School of Medicine, Seoul National University, Seoul, Korea.
authors.forename: B
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Health Promotion Center, Ilsan Paik Hospital, School of Medicine, Inje University, Goyang, Korea.
authors.forename: Y J
authors.identifier: http://orcid.org/0000-0003-3428-1587
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Health Promotion Center, Ilsan Paik Hospital, School of Medicine, Inje University, Goyang, Korea.
authors.forename: E S
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Health Promotion Center, Ilsan Paik Hospital, School of Medicine, Inje University, Goyang, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000328:Adult; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D004311:Double-Blind Method; D005221:Fatigue / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid