BACKGROUND & AIMS:Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by approximately 5% when given for 6-12 months. A pilot trial in 16 ADPKD patients demonstrated that sirolimus, an mTOR inhibitor, reduced PLD volume by 26%. The aim of this study was to assess the PLD volume reducing effect of everolimus and octreotide relative to octreotide monotherapy. METHODS: We designed a randomized controlled trial that compared 48 weeks of everolimus 2.5 mg daily, combined with octreotide 40 mg intramuscularly every 4 weeks, to octreotide monotherapy. We included PCLD and ADPKD patients. Exclusion criteria were MDRD-GFR <60 ml/min/1.73 m(2) and liver volume <2500 ml. Primary outcome was change in liver volume measured with CT-volumetry. RESULTS: We randomized 44 PLD patients (29 PCLD, 15 ADPKD, 89% female) to treatment withoctreotide (n=23) or octreotide-everolimus (n=21). Liver volume decreased by 3.5% (p<0.01) in the monotherapy arm, compared to 3.8% with combination therapy (p<0.01). The difference between treatment arms was not significant (p=0.73). CONCLUSIONS: Adding everolimus to octreotide in PLD does not increase the liver volume reducing effect of octreotide.
RCT Entities:
BACKGROUND & AIMS:Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by approximately 5% when given for 6-12 months. A pilot trial in 16 ADPKDpatients demonstrated that sirolimus, an mTOR inhibitor, reduced PLD volume by 26%. The aim of this study was to assess the PLD volume reducing effect of everolimus and octreotide relative to octreotide monotherapy. METHODS: We designed a randomized controlled trial that compared 48 weeks of everolimus 2.5 mg daily, combined with octreotide 40 mg intramuscularly every 4 weeks, to octreotide monotherapy. We included PCLD and ADPKDpatients. Exclusion criteria were MDRD-GFR <60 ml/min/1.73 m(2) and liver volume <2500 ml. Primary outcome was change in liver volume measured with CT-volumetry. RESULTS: We randomized 44 PLD patients (29 PCLD, 15 ADPKD, 89% female) to treatment with octreotide (n=23) or octreotide-everolimus (n=21). Liver volume decreased by 3.5% (p<0.01) in the monotherapy arm, compared to 3.8% with combination therapy (p<0.01). The difference between treatment arms was not significant (p=0.73). CONCLUSIONS: Adding everolimus to octreotide in PLD does not increase the liver volume reducing effect of octreotide.
Authors: Maria J Perugorria; Tatyana V Masyuk; Jose J Marin; Marco Marzioni; Luis Bujanda; Nicholas F LaRusso; Jesus M Banales Journal: Nat Rev Gastroenterol Hepatol Date: 2014-09-30 Impact factor: 46.802
Authors: Maria Lorenzo Pisarello; Tatyana V Masyuk; Sergio A Gradilone; Anatoliy I Masyuk; Jingyi F Ding; Pui-Yuen Lee; Nicholas F LaRusso Journal: Am J Pathol Date: 2018-01-31 Impact factor: 4.307
Authors: Myrte K Neijenhuis; Tom J G Gevers; Marie C Hogan; Patrick S Kamath; Titus F M Wijnands; Ralf C P M van den Ouweland; Marie E Edwards; Jeff A Sloan; Wietske Kievit; Joost P H Drenth Journal: Hepatology Date: 2016-04-15 Impact factor: 17.425