Lanreotide Reduces Liver/Kidney Volume in Polycystic Liver Disease: Presented at EASL

By Walter Alexander

VIENNA, Austria -- April 16, 2019 -- Treatment with somatostatin analogues should be considered in patients with enlarged liver and/or kidneys to prevent further disease progression, according to a subanalysis of the DIPAK 1 trial presented here at The International Liver Meeting, the 54th Annual Meeting of the European Association for the Study of the Liver (EASL).

Polycystic liver disease is the most frequent extra-renal manifestation of autosomal dominant polycystic kidney disease, said Joost P. H. Drenth, MD, Radboudumc, University Medical Center, Rotterdam, The Netherlands, on April 12, adding that there is an unmet need for treatment of the resultant hepatomegaly, which leads to symptomatic disease and reduced quality of life.

The processes involved with hepatic cell proliferation and fluid secretion that cause cyst formation and growth involve cyclic adenosine monophosphate. Somatostatin analogues inhibit cyclic adenosine monophosphate production, reducing liver volume.

Earlier trials of somatostatin analogues in polycystic liver disease have been limited by short follow-up and small sample sizes. Also, 6 to 12 months of treatment has been shown to bring only 3% to 5% reductions in combined liver and kidney volume, with effects achieved in the first months of treatment and diminishing thereafter.

The goal of DIPAK 1 was to investigate the long-term effect of the somatostatin analogue lanreotide on combined liver and kidney volume. DIPAK 1, an investigator-driven randomised, controlled, open-label trial with blinded endpoint analysis, included in this subanalysis 175 patients with autosomal dominant polycystic kidney disease, liver volume >2,000 mL, and an estimated glomerular filtration rate of 30 to 60 ml/min/1.73 m2. Included subjects received lanreotide 120 mg subcutaneously every 4 weeks or standard of care (blood pressure reduction). The primary outcome was change in height-adjusted total liver volume from baseline to the end of treatment at 120 weeks.

At 120 weeks, height-adjusted total liver volume decreased by 140 mL (-1.99%; 95% confidence interval [CI], -4.21 to 0.24) in the lanreotide treatment group, whereas it increased by 3.92% (95% CI, 1.56-6.28) in the standard-of-care group (treatment difference, -5.91%; 95% CI, -9.18 to -2.63; P< .001). Four months after the final lanreotide injection, a beneficial treatment effect was still evident (liver volume reduction, -3.87%; 95% CI, -7.55 to -0.18; P = .04). An even greater reduction in height-adjusted total liver and kidney volume of >350 mL was shown for lanreotide than for standard-of-care treatment (-7.18%; 95% CI, -10.25 to -4.12; P < .001).

“Long-term treatment with lanreotide resulted in a significant treatment effect of 5.91% on height-corrected total liver volume,” concluded Dr. Drenth, noting that the >350-mL reduction in combined liver and kidney volume is even more clinically important.

[Presentation title: Lanreotide Reduces Liver Growth in Autosomal Dominant Polycystic Kidney Disease: Data From a 120-Week Randomized Clinical Trial. Abstract PS-192]

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