Hedwig M A D'Agnolo1, Wietske Kievit2, R Bart Takkenberg3, Ioana Riaño4, Luis Bujanda4, Myrte K Neijenhuis1, Ellen J L Brunenberg5, Ulrich Beuers3, Jesus M Banales4, Joost P H Drenth6. 1. Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. 2. Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. 3. Department of Gastroenterology and Hepatology, Amsterdam Medical Center, Amsterdam, The Netherlands. 4. Department of Liver and Gastrointestinal Diseases, Biodonostia Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), IKERBASQUE, CIBERehd, San Sebastián, Spain. 5. Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands. 6. Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: joostphdrenth@cs.com.
Abstract
BACKGROUND & AIMS: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. METHODS: 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). RESULTS: 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). CONCLUSIONS: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. LAY SUMMARY: 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.
RCT Entities:
BACKGROUND & AIMS: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. METHODS: 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). RESULTS: 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 ADPKDpatients compared to ADPKD controls (p=0.049). CONCLUSIONS:UDCA administration for 24weeks did not reduce TLV in advanced PLD, but UDCA reduced LCV growth in ADPKDpatients. Future studies might explore whether ADPKD and ADPLD patients respond differently to UDCA treatment. LAY SUMMARY: 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: Paula Olaizola; Pedro M Rodrigues; Francisco J Caballero-Camino; Laura Izquierdo-Sanchez; Patricia Aspichueta; Luis Bujanda; Nicholas F Larusso; Joost P H Drenth; Maria J Perugorria; Jesus M Banales Journal: Nat Rev Gastroenterol Hepatol Date: 2022-05-13 Impact factor: 73.082
Authors: René M M van Aerts; Lucas H P Bernts; Tom J G Gevers; Wietske Kievit; Lisanne Koopmans; Theodoor E Nieboer; Frederik Nevens; Joost P H Drenth Journal: Clin Pharmacol Ther Date: 2019-07-23 Impact factor: 6.875
Authors: René M M van Aerts; Marieke Kolkman; Wietske Kievit; Tom J G Gevers; Frederik Nevens; Joost P H Drenth Journal: Therap Adv Gastroenterol Date: 2018-10-03 Impact factor: 4.409