Background:Somatostatin analogues (SAs) reduce liver volume and relief symptoms in polycystic liver disease (PLD). Its effect wears off after continuing therapy suggesting development of SA tolerance in patients on chronic therapy. We postulate that a drug holiday resensitizes the liver to its acute pharmacological effects. Therefore, this study examines the liver volume-reducing effect of SAs after a drug holiday.Methods:Patients were identified from the International PLD Registry and included in our analysis when (1) treated with SAs during two cycles separated by a drug holiday and (2) height-adjusted total liver volume (hTLV) was available at start and end of each cycle. For our primary outcome we compared the effect of SAs (in % per 6 months) on hTLV between the first and second treatment cycle.Results:In 34 patients, initial liver volume-reducing effect was similar to that after rechallenge [−2.6% per 6 months (interquartile range, −3.8–0.8) versus −1.6% per 6 months (interquartile range, −3.1–1.1), p = 0.510]. Cessation of treatment led to a rebound effect, but liver volume remained stable compared with the baseline with intermittent therapy in responders to SA [−0.6% (interquartile range, −7.4–5.7) after 46.5 months].Conclusions:PLD patients treated with SAs benefit from retreatment after a drug holiday. The significant increase of liver volume after cessation of treatment complicates widespread use of a drug holiday as new treatment strategy. Our results contribute to a better understanding of the pharmacological effect of SAs and help to identify patients who might benefit.

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