Research ArticleUrsodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial

Background & AimsUrsodeoxycholic 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.MethodsWe conducted an international, multicenter, randomized controlled trial in symptomatic PLD patients from three tertiary referral centers. Patients with PLD and total liver volume (TLV) ⩾2500 ml were randomly assigned to UDCA treatment (15-20 mg/kg/day) for 24 weeks, 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).ResultsWe 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 6697 ml to 6954 ml) after 24 weeks of UDCA treatment compared to 3.1 ± 3.8% (mean TLV increased from 5512 ml to 5724 ml) in the control group (p = 0.493). LCV was not different after 24 weeks between controls and UDCA treated patients (p = 0.848). However, UDCA inhibited LCV growth in ADPKD patients compared to ADPKD controls (p = 0.049).ConclusionsUDCA administration for 24 weeks 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 summaryCurrent 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.

Graphical abstractDownload high-res image (137KB)Download full-size image