Of note, changes in total liver volumes on octreotide strongly correlated with concomitant changes in total kidney volumes. Evidence that this correlation was observed CHIR99021 CAS during octreotide therapy, but not during placebo, corroborates the hypothesis that octreotide-associated changes in liver and kidney volumes reflected a specific treatment effect rather than the natural history of the disease. Treatment was also well tolerated and was not associated with any clinically relevant change in any considered safety parameter. Indeed, only two patients prematurely withdrew from the trial because of asthenia reported after 3 months of placebo treatment in one case and detection of two nonsymptomatic gallstones at per-protocol ultrasound evaluation after 5 months of treatment with octreotide in the second case.

Notably, this adverse event fully recovered with the dissolution of the gallstones over 2 months of treatment with ursodeoxycholate acid. Two patients with ADPKD and liver cysts were previously reported to have reduction in liver volumes during 4 and 8 months of octreotide therapy, respectively (14); however, data were uncontrolled and, most important, were confounded by concomitant treatments such as cyst aspiration or fenestration/ablation, which conceivably contributed to the reduction in liver volumes. Another clinical trial run in parallel with and independent of the study presented here found that a treatment period of the same duration (6 months) with another long-acting somatostatin analogue (lanreotide) achieved a reduction of liver volume in patients with autosomal-dominant polycystic liver disease or ADPKD (15) similar to the reduction we observed in ADPKD patients.

Finding that lanreotide also limited the growth of kidney volumes in the subgroup of patients with ADPKD confirmed and extended our previous data that the growth of ADPKD kidneys can be prevented by octreotide therapy (6). Of interest, in the study presented here octreotide-induced reduction in total liver volume was explained by the concomitant reduction in parenchyma volume without appreciable changes in macroscopic cyst volumes. We speculate that apparently normal parenchymal volume might include overgrown bile ductules and cysts with volumes smaller than the detection threshold of the CT scan evaluation (6), and that the reduction of these volumes might explain the reduction in the parenchymal volume we observed during octreotide treatment.

This is consistent with in vitro Entinostat evidence that octreotide-inhibited proliferation of cholangiocytes from rats with polycystic liver disease reduced the circumferential area of bile ducts and of new cysts even before the development of macroscopic cysts (4). However, larger studies are needed to confirm or reject the hypothesis that octreotide might reduce liver parenchyma volume because of its effects on smaller cysts.