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The goal of this study was to compare the clinical features of patients with isolated polycystic liver disease (PCLD) with those of patients with polycystic liver and autosomal dominant polycystic kidney disease (ADPKD).Cases were identified from clinical records at the University of Colorado Hospital in Denver (USA) and at the Radboud University Hospital in Nijmegen (the Netherlands) by ICD-10 codes. To be included in this analysis, patients had to have an initial diagnosis of PCLD within six years of presentation to our clinics. Medical records were reviewed for demographic information, medical history, physical examination, symptoms, complications, laboratory and imaging results, therapy and outcomes.Out of a total of 94, 53 patients met our criteria for entering this study, 19 with PCLD and 34 with ADPKD. The mean time interval from diagnosis of PCLD to presentation in our clinics was 1.21 years for PCLD and 2.76 years for ADPKD (P=NS). PCLD was associated with female gender in both PCLD and ADPKD. Patients with PCLD had greater numbers (P=0.031), and larger sizes of liver cysts (P=0.0051), but had less associated morbidities than patients with ADPKD. Liver cyst decompressions were performed more frequently in PCLD patients (57.9 vs. 23.5%, P=0.012). However, serious hepatic complications, sufficient to require consideration of liver transplantation, were more frequent in patients with ADPKD (0/19 vs. 6/34, P<0.0001).Although PCLD in patients with PCLD is characterized by larger and greater number of hepatic cysts, the clinical course is relatively benign compared with ADPKD.