Risk Factors for the Development of Hepatic Cysts in Autosomal Dominant Polycystic Kidney Disease PATRICIA zyxwvut A. GABOW, A" M. JOHNSON, WILLIAM D. KAEHNY, MICHAEL L. MANCO-JOHNSON, zy Department zyxwvutsr of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262 IRENE T. DULEY AND GREGORY T. EVERSON Hepatic cysts are a m&or manifestation zyxwv of auto- somal dominant polycystic kidney disease. This study examined 239 autosomal dominant polycystic kidney disease patients and 189 unaffected family members to define the factors that influence the presence and severity of hepatic cysts. Autosomal dominant poly- cystic kidney disease patients with hepatic cysts were older than autosomal dominant polycystic kidney disease patients without such cysts (44.6 f 1.1 yr vs. 32.9 zyxwvutsrq & 1.1 yr; p < 0.0001). The number of hepatic cysts increased with age (r = 0.43; p < 0.0001). Women were more likely to have massive hepatic cystic disease (>15 cysts) than men (p < 0.04). Women also had larger maximal cyst size (4.2 f 0.4 cm vs. 2.7 f 0.3 cm; p < 0.004). Women with hepatic cysts were more likely to have been pregnant (p < 0.001) and to have had more pregnancies (2.9 f 0.3 pregnancies vs. 1.6 f 0.2 pregnancies; p < 0.0009). Kidney volume (p < O.OOOl), number of cysts (p < zyxwvu 0.004), percen- tage of cystic parenchyma (p < 0.001) and predom- inant cyst size (p < 0.001) were greater and creatinine clearance was lower (64.5 f 3.1 mUmid1.73 mp vs. 94.5 -C 3.4 mlimi41.73 ma; p < 0.001) in autosomal dominant polycystic kidney disease patients with he- patic cysts. By logistic regression, the frequency of hepatic cysts was related to increased age, increased severity of renal cystic disease and decreased crea- tinine clearance. Number and size of hepatic cysts correlated with the occurrence of pregnancy, female gender, increased age and severity of the renal lesion. In conclusion, the hepatic expression of the autosomal dominant polycystic kidney disease gene appears to be modulated by age, female gender, pregnancy, severity Received September 19, 1989; accepted January 22, 1990. This research was supported by grant 5 PO1 DK34039, Human Polycystic Kidney Disease (PKD), awarded by the Department of Health and Human Services, Public Health Service, National Institute of Diabetes and Digestive and Kidney Diseases and grant RR-00051, General Clinical Research Centers Program from the Division of Research Resources, National Institutes of Health. These data were presented at the 1989 National Meeting of the American Gastroenterology Association and the 1987 National Meeting of the American Society of Nephrology. These data were published in zyxwvutsrq Gastroenterology and Kidney International in abstract form. Address reprint requests to: Patricia Gabow, M.D., UCHSCBox C283,4200 East Ninth Avenue, Denver, CO 80262. 31/1/20961 of the renal lesion and kidney function. (&PATOLOGY 1990; 11:1033-1037.) Polycystic liver is a common manifestation of auto- somal dominant polycystic kidney disease (ADPKD) (1-3). Previous reports have suggested that the preva- lence of hepatic cysts increases with age (2, 3) and may correlate with kidney dysfunction (3). Although women may be more susceptible to development of hepatic cystic disease (4, 5), no information exists regarding the relationship of pregnancy to hepatic cyst formation. No systematic assessment has been made of these factors or of their potential interactions in regulating expression of hepatic cysts. Moreover, no data exist on the rela- tionship of hepatic cyst formation to renal cysts and to other common extrarenal manifestations. In addition, familial clustering occurs in intracranial aneurysms in ADPKD but has not been examined for hepatic cysts (6). Thus we tested for the presence of familial clustering of hepatic cystic disease. We used multinomial and multivariate logistic regression analysis to determine the relationships of age, gender, pregnancy, kidney function, degree of renal cystic disease and presence of other extrarenal manifestations to hepatic cystic disease in a prospectively studied population of 239 subjects with ADPKD and 189 unaffected family members. MATERIALS AND METHODS All subjects were studied in the Clinical Research Center of the University of Colorado Health Sciences Center from June 1985 to August 1988 as part of a large, ongoing study of polycystic kidney disease in families. The study was approved by the Human Subjects Committee and the Clinical Research Center of the University of Colorado Health Sciences Center. All subjects gave written, informed consent. Each subject underwent a formal interview, physical examination and abdominal ultrasonography. No subject entered the study for primary diagnosis of polycystic liver disease. Blood was obtained in most ADPKD subjects for measurement of bilirubin (n = 2281, AST (n = 229) and y-glutamyltransferase (n = 218) to determine whether he- patic cysts altered routine tests of liver function. A serum creatinine measurement (n = 234) and two consecutive 24-hr urine collections were obtained for determination of creatinine 1033