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

D’Agnolo, Hedwig M. A.; Kievit, Wietske; Takkenberg, R. Bart; Riaño, Ioana; Bujanda, Luís; Neijenhuis, Myrte K.; Brunenberg, E.; Beuers, Ulrich; Bañales, Jesús M.; Drenth, Joost P.H.

doi:10.1016/j.jhep.2016.05.009

Cited by 44 publications

(47 citation statements)

References 31 publications

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“…Ursodeoxycholic acid (UDCA) has also been proposed as medical therapy for PLD, as it inhibits cholangiocyte proliferation in vitro and in murine models . However, a phase‐2 randomized controlled trial showed no benefit on growth of total liver volume . We were unable to find any data on the effect of UDCA on ascites or portal hypertension in PLD.…”

Section: Management Of Portal Hypertension In Pldmentioning

confidence: 92%

Management of portal hypertension and ascites in polycystic liver disease

Bernts

Drenth

Tjwa

2019

Liver International

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Patients suffering from polycystic liver disease may develop Hepatic Venous Outflow Obstruction, Portal Vein Obstruction and/or Inferior Caval Vein Syndrome because of cystic mass effect. This can cause portal hypertension, leading to ascites, variceal haemorrhage or splenomegaly. For this review, we evaluate the evidence to provide clinical guidance for physicians faced with this complication. Diagnosis is made with imaging such as ultrasound, computed tomography or magnetic resonance imaging. Therapy includes conventional therapy with diuretics and paracentesis, and medical therapy using somatostatin analogues. Based on disease phenotype various (non‐)surgical liver‐volume reducing therapies, hepatic or portal venous stenting, transjugular intrahepatic portosystemic shunts and liver transplantation may be considered. Because of complicated anatomy, use of high‐risk interventions and lack of empirical evidence, patients should be treated in expert centres.

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Section: Management Of Portal Hypertension In Pldmentioning

confidence: 92%

Management of portal hypertension and ascites in polycystic liver disease

Bernts

Drenth

Tjwa

2019

Liver International

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“…Total liver volume was measured by assessing CT or MRI scans using (semi‐) automatic software as available in the participating centres. In the Netherlands, TLV on CT was measured by 3D measurement of CT scan slices using Pinnacle3 ® version 8.0 (Philips, Eindhoven, The Netherlands) . TLV measuring on MRI was performed with Analyze 11 software (AnalyzeDirect Inc, Overland Park, KS, USA) using a stereology method .…”

Section: Methodsmentioning

confidence: 99%

“…All imaging was performed as part of routine clinical care (eg, symptomatic disease, incidental finding, and familial screening) or in clinical trials. All liver volumes measured for trial purposes were measured blindly according to the study protocol . Liver volumetry for routine clinical care was performed by a trained physician (RvA).…”

Section: Methodsmentioning

confidence: 99%

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Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Aerts

Kievit

Jong

et al. 2018

Liver International

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“…In addition, the proliferation of ADPKD human cholangiocytes stimulated by the toxic and pro-mitotic bile acid GDCA was blocked by both UDCA and TUDCA. As a consequence of these beneficial effects and the safety of UDCA administration to humans, an International Multicenter Randomized Control Phase II Clinical Trial (CURSOR) was performed [44] . Thirty-two highly symptomatic PLD patients (16 ADPKD and 16 APLD) with >20 cysts and TLV ≥ 2,500 ml were included and randomized in the study (15 with UDCA-treatment and 17 without treatment).…”

Section: Udca As a Novel Therapeutic Strategy For Pldsmentioning

confidence: 99%

Bile Acids in Polycystic Liver Diseases: Triggers of Disease Progression and Potential Solution for Treatment

Labiano¹,

Esparza-Baquer²,

Marzioni³

et al. 2017

Dig Dis

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Polycystic liver diseases (PLDs) are a group of genetic hereditary cholangiopathies characterized by the development and progressive growth of cysts in the liver, which are the main cause of morbidity. Current therapies are based on surgical procedures and pharmacological strategies, which show short-term and modest beneficial effects. Therefore, the determination of the molecular mechanisms of pathogenesis appears to be crucial in order to find new potential targets for pharmacological therapy. Ductal plate malformation during embryogenesis and abnormal cystic cholangiocyte growth and secretion are some of the key mechanisms involved in the pathogenesis of PLDs. However, the discovery of the presence of bile acids in the fluid collected from human cysts and the intrahepatic accumulation of cytotoxic bile acids in an animal model of PLD (i.e. polycystic kidney (PCK) rat) suggest a potential role of impaired bile acid homeostasis in the pathogenesis of these diseases. On the other hand, ursodeoxycholic acid (UDCA) has emerged as a new potential therapeutic tool for PLDs by promoting the inhibition of cystic cholangiocyte growth in both PCK rats and highly symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD: most common type of PLD), and improving symptoms. Chronic treatment with UDCA normalizes the decreased intracellular calcium levels in ADPKD human cholangiocytes in vitro, which results in the reduction of their baseline-stimulated proliferation. Moreover, UDCA decreases the liver concentration of cytotoxic bile acids in PCK rats and the bile acid-dependent enhanced proliferation of cystic cholangiocytes. Here, the role of bile acids in the pathogenesis of PLDs and the potential therapeutic value of UDCA for the treatment of these diseases are reviewed and future lines of investigation in this field are proposed.

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

Cited by 44 publications

References 31 publications

Management of portal hypertension and ascites in polycystic liver disease

Management of portal hypertension and ascites in polycystic liver disease

Severity in polycystic liver disease is associated with aetiology and female gender: Results of the International PLD Registry

Bile Acids in Polycystic Liver Diseases: Triggers of Disease Progression and Potential Solution for Treatment

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