title: Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial.
abstract: Ursodeoxycholic acid (UDCA) inhibits proliferation of polycystic human cholangiocytes in vitro and hepatic cystogenesis in a rat model of polycystic liver disease (PLD) in vivo. Our aim was to test whether UDCA may beneficially affect liver volume in patients with advanced PLD.
  
  
  
  We conducted an international, multicenter, randomized controlled trial in symptomatic PLD patients from three tertiary referral centers. Patients with PLD and total liver volume (TLV) ⩾2500ml were randomly assigned to UDCA treatment (15-20mg/kg/day) for 24weeks, or to no treatment. Primary endpoint was proportional change in TLV. Secondary endpoints were change in symptoms and health-related quality of life. We performed a post-hoc analysis of the effect of UDCA on liver cyst volume (LCV).
  
  
  
  We included 34 patients and were able to assess primary endpoint in 32 patients, 16 with autosomal dominant polycystic kidney disease (ADPKD) and 16 with autosomal dominant polycystic liver disease (ADPLD). Proportional TLV increased by 4.6±7.7% (mean TLV increased from 6697ml to 6954ml) after 24weeks of UDCA treatment compared to 3.1±3.8% (mean TLV increased from 5512ml to 5724ml) in the control group (p=0.493). LCV was not different after 24weeks between controls and UDCA treated patients (p=0.848). However, UDCA inhibited LCV growth in ADPKD patients compared to ADPKD controls (p=0.049).
  
  
  
  UDCA administration for 24weeks did not reduce TLV in advanced PLD, but UDCA reduced LCV growth in ADPKD patients. Future studies might explore whether ADPKD and ADPLD patients respond differently to UDCA treatment.
  
  
  
  Current therapies for polycystic liver disease are invasive and have high recurrence risks. Our trial showed that the drug, ursodeoxycholic acid, was not able to reduce liver volume in patients with polycystic liver disease. However, a subgroup analysis in patients that have kidney cysts as well showed that liver cyst volume growth was reduced in patients who received ursodeoxycholic acid in comparison to patients who received no treatment. Trial registration number https://www.clinicaltrials.gov/: NCT02021110. EudraCT Number https://www.clinicaltrialsregister.eu/: 2013-003207-19.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Hedwig M A
authors.initials: HM
authors.lastname: D'Agnolo
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
authors.forename: Wietske
authors.initials: W
authors.lastname: Kievit
authors.affiliation: Department of Gastroenterology and Hepatology, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: R Bart
authors.initials: RB
authors.lastname: Takkenberg
authors.affiliation: Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), IKERBASQUE, CIBERehd, San Sebastián, Spain.
authors.forename: Ioana
authors.initials: I
authors.lastname: Riaño
authors.affiliation: Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), IKERBASQUE, CIBERehd, San Sebastián, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Myrte K
authors.initials: MK
authors.lastname: Neijenhuis
authors.affiliation: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ellen J L
authors.initials: EJ
authors.lastname: Brunenberg
authors.affiliation: Department of Gastroenterology and Hepatology, Amsterdam Medical Center, Amsterdam, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.affiliation: Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), IKERBASQUE, CIBERehd, San Sebastián, Spain.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Banales
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: joostphdrenth@cs.com.
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
mesh_terms: D003560:Cysts; D006801:Humans; D008107:Liver Diseases; D016891:Polycystic Kidney, Autosomal Dominant; D011788:Quality of Life; D014580:Ursodeoxycholic Acid
chemical_list: D014580:Ursodeoxycholic Acid
keywords: Autosomal dominant polycystic kidney disease; CT volumetry; Polycystic liver disease; Quality of life; Ursodeoxycholic acid