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

Autor: Ulrich Beuers, Jesus M. Banales, Hedwig M. A. D'Agnolo, E. Brunenberg, Luis Bujanda, Ioana Riaño, Myrte K. Neijenhuis, Wietske Kievit, R. Bart Takkenberg, Joost P.H. Drenth
Přispěvatelé: Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology
Rok vydání: 2016
Předmět:
medicine.medical_specialty
Autosomal dominant polycystic kidney disease
Kidney cysts
Gastroenterology
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Internal medicine
Clinical endpoint
medicine
Polycystic kidney disease
Humans
Gamma-glutamyltransferase
Hepatology
biology
business.industry
Cysts
Polycystic liver disease
Liver Diseases
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Ursodeoxycholic Acid
medicine.disease
Polycystic Kidney
Autosomal Dominant
Ursodeoxycholic acid
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]
Endocrinology
030220 oncology & carcinogenesis
Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]
biology.protein
Quality of Life
030211 gastroenterology & hepatology
medicine.symptom
business
medicine.drug
Zdroj: Journal of Hepatology, 65, 601-7
Journal of Hepatology, 65, 3, pp. 601-7
Journal of hepatology, 65(3), 601-607. Elsevier
ISSN: 1600-0641
0202-1110
0168-8278
Popis: Contains fulltext : 171894.pdf (Publisher’s version ) (Closed access) 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.
Databáze: OpenAIRE
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