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

Journal of Hepatology

Volumn 65, Issue 3, 2016, Pages 601-607

  D'Agnolo, Hedwig M A ^a   Kievit, Wietske ^a   Takkenberg, R Bart ^b   Riaño, Ioana ^c   Bujanda, Luis ^c   Neijenhuis, Myrte K ^a   Brunenberg, Ellen J L ^a   Beuers, Ulrich ^b   Banales, Jesus M ^c   Drenth, Joost P H ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c HOSPITAL DONOSTIA   (Spain)

Author keywords

Autosomal dominant polycystic kidney disease; CT volumetry; Polycystic liver disease; Quality of life; Ursodeoxycholic acid

Indexed keywords

GAMMA GLUTAMYLTRANSFERASE; URSODEOXYCHOLIC ACID;

ADULT; ARTICLE; AUTOSOMAL DOMINANT DISORDER; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; FEMALE; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HUMAN; KIDNEY POLYCYSTIC DISEASE; KIDNEY SIZE; LIVER CYST; LIVER POLYCYSTIC DISEASE; LIVER WEIGHT; MALE; MEDICATION COMPLIANCE; MULTICENTER STUDY; PATIENT COMPLIANCE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SHORT FORM 36; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; CLINICAL TRIAL; CYST; LIVER DISEASE;

CYSTS; HUMANS; LIVER DISEASES; POLYCYSTIC KIDNEY, AUTOSOMAL DOMINANT; QUALITY OF LIFE; URSODEOXYCHOLIC ACID;

EID: 84977668235     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2016.05.009     Document Type: Article

References (31)

1. [1] Gevers, T.J., Drenth, J.P., Diagnosis and management of polycystic liver disease. Nat Rev Gastroenterol Hepatol 10 (2013), 101–108.
2. [2] Bae, K.T., Zhu, F., Chapman, A.B., Torres, V.E., Grantham, J.J., Guay-Woodford, L.M., et al. Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol 1 (2006), 64–69.
3. [3] Wijnands, T.F., Neijenhuis, M.K., Kievit, W., Nevens, F., Hogan, M.C., Torres, V.E., et al. Evaluating health-related quality of life in patients with polycystic liver disease and determining the impact of symptoms and liver volume. Liver Int 34 (2014), 1578–1583.
4. [4] Hoevenaren, I.A., Wester, R., Schrier, R.W., McFann, K., Doctor, R.B., Drenth, J.P., et al. Polycystic liver: clinical characteristics of patients with isolated polycystic liver disease compared with patients with polycystic liver and autosomal dominant polycystic kidney disease. Liver Int 28 (2008), 264–270.
5. [5] Drenth, J.P., Chrispijn, M., Nagorney, D.M., Kamath, P.S., Torres, V.E., Medical and surgical treatment options for polycystic liver disease. Hepatology 52 (2010), 2223–2230.
6. [6] Caroli, A., Antiga, L., Cafaro, M., Fasolini, G., Remuzzi, A., Remuzzi, G., et al. Reducing polycystic liver volume in ADPKD: effects of somatostatin analogue octreotide. Clin J Am Soc Nephrol 5 (2010), 783–789.
7. [7] Gevers, T.J., Hol, J.C., Monshouwer, R., Dekker, H.M., Wetzels, J.F., Drenth, J.P., Effect of lanreotide on polycystic liver and kidneys in autosomal dominant polycystic kidney disease: an observational trial. Liver Int 35 (2015), 1607–1614.
8. [8] Chrispijn, M., Nevens, F., Gevers, T.J., Vanslembrouck, R., van Oijen, M.G., Coudyzer, W., et al. The long-term outcome of patients with polycystic liver disease treated with lanreotide. Aliment Pharmacol Ther 35 (2012), 266–274.
9. [9] Cnossen, W.R., te Morsche, R.H., Hoischen, A., Gilissen, C., Chrispijn, M., Venselaar, H., et al. Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis. Proc Natl Acad Sci U S A 111 (2014), 5343–5348.
10. [10] Perugorria, M.J., Masyuk, T.V., Marin, J.J., Marzioni, M., Bujanda, L., LaRusso, N.F., et al. Polycystic liver diseases: advanced insights into the molecular mechanisms. Nat Rev Gastroenterol Hepatol 11 (2014), 750–761.
11. [11] Banales, J.M., Masyuk, T.V., Gradilone, S.A., Masyuk, A.I., Medina, J.F., LaRusso, N.F., The cAMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD). Hepatology 49 (2009), 160–174.
12. [12] Harris, P.C., Torres, V.E., Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J Clin Invest 124 (2014), 2315–2324.
13. [13] Masyuk, T.V., Masyuk, A.I., Torres, V.E., Harris, P.C., Larusso, N.F., Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3′,5′-cyclic monophosphate. Gastroenterology 132 (2007), 1104–1116.
14. [14] Beuers, U., Nathanson, M.H., Isales, C.M., Boyer, J.L., Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes extracellular Ca++ mechanisms defective in cholestasis. J Clin Invest 92 (1993), 2984–2993.
15. [15] Marzioni, M., Francis, H., Benedetti, A., Ueno, Y., Fava, G., Venter, J., et al. Ca2+-dependent cytoprotective effects of ursodeoxycholic and tauroursodeoxycholic acid on the biliary epithelium in a rat model of cholestasis and loss of bile ducts. Am J Pathol 168 (2006), 398–409.
16. [16] Banales, J.M., Masyuk, T.V., Bogert, P.S., Huang, B.Q., Gradilone, S.A., Lee, S.O., et al. Hepatic cystogenesis is associated with abnormal expression and location of ion transporters and water channels in an animal model of autosomal recessive polycystic kidney disease. Am J Pathol 173 (2008), 1637–1646.
17. [17] Munoz-Garrido, P., Marin, J.J., Perugorria, M.J., Urribarri, A.D., Erice, O., Saez, E., et al. Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease. J Hepatol 63 (2015), 952–961.
18. [18] Hempfling, W., Dilger, K., Beuers, U., Systematic review: ursodeoxycholic acid–adverse effects and drug interactions. Aliment Pharmacol Ther 18 (2003), 963–972.
19. [19] Pei, Y., Obaji, J., Dupuis, A., Paterson, A.D., Magistroni, R., Dicks, E., et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol 20 (2009), 205–212.
20. [20] Chrispijn, M., Gevers, T.J., Hol, J.C., Monshouwer, R., Dekker, H.M., Drenth, J.P., Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: results from a randomized controlled trial. J Hepatol 59 (2013), 153–159.
21. [21] Gevers, T.J., Chrispijn, M., Wetzels, J.F., Drenth, J.P., Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease. BMC Nephrol, 13, 2012, 17.
22. [22] Ruggenenti, P., Remuzzi, A., Ondei, P., Fasolini, G., Antiga, L., Ene-Iordache, B., et al. Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int 68 (2005), 206–216.
23. [23] Perona, P., Malik, J., Scalespace and edge detection using anisotropic diffusion. IEEE Trans Pattern Anal Mach Intell 12 (1990), 629–639.
24. [24] N O. A threshold selection method from gray-level histogram. IEEE Transactions on SMC 8 1978:62–66.
25. [25] Neijenhuis, M.K., Gevers, T.J., Hogan, M.C., Kamath, P.S., Wijnands, T.F., van den Ouweland, R.C.P.M., et al. Development and validation of a disease-specific questionnaire to assess patient-reported symptoms in polycystic liver disease. Hepatology, 2016, 10.1002/hep.28545.
26. [26] van Marrewijk, C.J., Mujakovic, S., Fransen, G.A., Numans, M.E., de Wit, N.J., Muris, J.W., et al. Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial. Lancet 373 (2009), 215–225.
27. [27] Bovenschen, H.J., Janssen, M.J., van Oijen, M.G., Laheij, R.J., van Rossum, L.G., Jansen, J.B., Evaluation of a gastrointestinal symptoms questionnaire. Dig Dis Sci 51 (2006), 1509–1515.
28. [28] van Keimpema, L., Nevens, F., Vanslembrouck, R., van Oijen, M.G., Hoffmann, A.L., Dekker, H.M., et al. Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology 137 (2009), 1661–1668 e1–e2.
29. [29] Iijima, T., Hoshino, J., Suwabe, T., Sumida, K., Mise, K., Kawada, M., et al. Ursodeoxycholic acid for treatment of enlarged polycystic liver. Ther Apher Dial 20 (2016), 73–78.
30. [30] Beuers, U., Drug insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol 3 (2006), 318–328.
31. [31] Urribarri, A.D., Munoz-Garrido, P., Perugorria, M.J., Erice, O., Merino-Azpitarte, M., Arbelaiz, A., et al. Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases. Gut 63 (2014), 1658–1667.