Radiology_Aug04 Abstract A 65-year-old man was referred to the Gastroenterology Department with complaints of longstanding upper abdominal discomfort and hepato- megaly. Ultrasound of the liver revealed a massively enlarged liver with multiple cystic areas. Aspiration of the largest cyst revealed 15 ml of yellow fluid without any organisms or malignant cells. A diagnosis of autoso- mal-dominant polycystic kidney dis- ease was suspected, but could not ini- tially be confirmed on ultrasound/ computed tomography imaging. Magnetic resonance imaging con- firmed the multiple hepatic cysts and revealed multiple smaller cysts in both kidneys. Symptomatology subsided after aspiration of the largest cyst and the patient was discharged. The patient has subsequently been fol- lowed up and is currently symptom free. The case illustrates the impor- tance of screening for associated kid- ney disease in patients with polycystic liver disease. Introduction Polycystic liver disease (PCLD) occurs most commonly as a manifes- tation of all forms of polycystic kidney disease, but especially autosomal- dominant polycystic kidney disease (ADPKD).1-5 It also occurs much more rarely as a disease entity on its own and is termed autosomal- dominant polycystic liver disease (ADPLD).4-6 The association of multi- ple hepatic cysts with kidney disease and the clinical implications thereof are, however, of primary relevance, as is demonstrated by our clinical case. Radiologically, PCLD must be dif- ferentiated from common hepatic cysts that occur in at least 2.5% of the population, multiple echinococcus cysts, cystic metastases, acquired cysts from trauma or infection, biliary cyst- adenoma and the clinically insignifi- cant and rare Von Meyenburg com- plexes.7,8 Case report A 65-year-old man was referred from a general practitioner to the Gastroenterology Department with vague complaints of longstanding upper abdominal discomfort and hepatomegaly. Past history was unre- markable other than the intake of tra- ditionally brewed beer. Clinical exam- ination revealed 21 cm hepatomegaly and the initial suspicion was that of alcoholic liver cirrhosis or haemo- siderosis. Biochemical investigations done before the ultrasound appoint- ment were aimed at excluding infec- tions, neoplasms and impaired liver and kidney function. Liver enzymes and liver function tests were all nor- mal other than a raised gamma- glutamyl transpeptidase of 176 IU/l and a serum albumin slightly below normal at 35 g/dl. Uric acid was increased to 0.48 mmol/l. Protein electrophoresis was normal, as were tests for haemostasis. The erythrocyte sedimentation rate was 31 mm/h and C-reactive protein below 5 mg/l. Virology for hepatitis A, B and C were all negative and serology was negative for echinococcus and bilharzia. Tumour markers including carcino- embryonic antigen, alpha-fetoprotein and prostate- specific antigen were in the normal reference range. Ultrasound (Fig. 1) of the liver revealed a massively enlarged liver 10 cm below the ribs in the midaxil- lary line distending across the midline to the left hypochondrium. Multiple cystic areas with posterior enhance- ment were visible without any obvi- ous characteristics of echinococcus 34 SA JOURNAL OF RADIOLOGY • August 2004 CASE REPORTS Polycystic liver disease — a disease entity presenting as part of autosomal- dominant polycystic kidney disease H Boonzaier-Botha MB ChB Department of Diagnostic Radiology University of the Free State and Universitas Hospital Bloemfontein C Cock MB ChB, MMed (Int) Department of Gastroenterology University of the Free State and Universitas Hospital Bloemfontein cysts. A single simple cortical cyst measured 21 mm x 20 mm in the lower pole of the left kidney. Helical computed tomography (CT) scan (GE Prospeed SX Advan- tage Helical) pre IV contrast (Fig. 2a) and post IV contrast (Fig. 2b) with oral contrast confirmed the multiple hepatic cysts and single simple cortical cyst in the lower pole of the left kid- ney. The multiple liver cysts varied in size with a maximum diameter of approximately 8 cm and no enhance- ment post intravenous contrast injec- tion. A single enlarged pre-aortic node was visible without notable abnor- malities in the rest of the abdominal structures. Aspiration of the largest cyst revealed 15 ml of yellow fluid without any organisms or malignant cells. Magnetic resonance imaging (MRI, GE Signa Twinspeed 1.5 T unit) confirmed the multiple hepatic cysts with low signal on T1-weighted images (Fig. 3a) and high signal on T2-weighted images (Figs 3b and 3c) without enhancement post gadolini- um injection. The hepatic cysts were initially accurately imaged with ultra- sound and no extra information regarding the characteristics of the hepatic cysts was revealed with CT or MR investigations. These investiga- tions were done for comparative pur- poses and confirmation of initial diag- nosis of PCLD. MR imaging, however, revealed multiple smaller cysts in both kidneys (Fig. 3d). A diagnosis of ADPKD, which had not been suspect- ed on clinical features or ultra- sound/CT imaging, was made. Based on the MRI findings a 24- hour urine protein concentration and creatinine clearance were done, but were found to be within normal lim- its. The patient was not hypertensive and fundoscopic examination was normal. Symptomatology subsided after aspiration of the largest cyst and the patient was discharged with the addi- tion of a short course of sucralfate. He has subsequently been followed up at the Gastroenterology Clinic and is CASE REPORTS 35 SA JOURNAL OF RADIOLOGY • August 2004 Fig.1. Ultrasound of enlarged liver. Fig. 2a. Helical computerised tomography pre IV contrast confirming hepatic and cortical cysts. Fig. 2b. Helical computerised tomography post IV contrast confirming hepatic and cortical cysts. Fig. 3a. MRI confirming multiple hepatic cysts with low signal on T1-weighted images. Fig. 3b. MRI confirming multiple hepatic cysts with high signal on T2-weighted images. Fig. 3c. MRI confirming multiple hepatic cysts with high signal on T2-weighted images. currently symptom free. Screening of his living relatives, by ultrasound and biochemistry, has revealed active ADPKD in one of his three children. Discussion PCLD usually occurs as a manifes- tation of ADPKD and can occur with ADPKD-1 (type 1) and ADPKD-2 (type 2).1-5 It can, however, also rarely occur as a separate entity distinct from ADPKD4-6 or a manifestation of auto- somal recessive polycystic kidney dis- ease.2,9,10 In adult patients PCLD is most commonly associated with ADPKD types 1 and 2. In these disorders there is abnormal formation of the protein polycystin, coded for by chromosome 16 (ADPKD type 1) and chromosome 4 (ADPKD type 2).3-5 In primary PCLD there is abnormal formation of hepatocystin coded for by chromo- some19.11-13 Polycystin and hepato- cystin play a role in the processing of secretary and transmembrane pro- teins that include receptors for the control of cell proliferation in the liver, kidneys, pancreas and spleen (and abnormalities thereof may lead to cyst formation in these organs).4,14,15 In children PCLD may be associa- ted with congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. The disease process in the recessive form is much more malignant and survival into adult- hood is rare.4 Radiologically the disease is char- acterised by the presence of multiple (4 or more) cysts imaged on ultra- sound, CT or MRI.7 Hepatic cysts are presumed to occur in 2.5% of the population and can be single or mul- tiple as part of ADPKD-1 and 2. They are developmental anomalies origi- nating from hamartomatous tissue. The cysts contain serous fluid and are lined by a thin wall of cuboidal epithe- lium, identical to that of the bile ducts, with a fibrous stroma underneath.7 Most cysts are asymptomatic but one- sixth of them cause symptoms due to liver enlargement or pressure on sur- rounding organs.16 Malignant degeneration of hepatic cysts is very rare but has to be exclud- ed by means of aspiration cytology before diagnosis is confirmed or symptomatic cysts are treated. Simple cysts are round, oval lesions with pos- terior enhancement and are echo-free. Thin septations can usually be seen on imaging.8 Associated cysts can be found in the kidneys in 50% of cases as well as in the pancreas, spleen and other organs.8 Ultrasound is usually superior to CT or MRI and depicts the well-defined, anechoic, round or oval lesions with imperceptible walls, thin septae and good posterior enhance- ment or through transmission. Ultrasound is also used for aspira- tion of cystic contents and interven- tional treatment of symptomatic cysts. The cysts can be inhomoge- neous due to haemorrhage inside and must then be differentiated from cys- tic metastasis.7 Haemorrhage and infection can cause debris-like echoes in the affected cysts on ultrasound which are then difficult to differentiate from cystic metastases that occur for example in squamous cell carcinoma and gastric stromal tumours.8 Hydatid disease of the liver can usually be dif- ferentiated by the typical sonographic appearance of the cyst wall and due to visible bands of delaminated endo- cysts. This is usually described as a ‘water-lily sign’.8 Calcification of the echinococcus cyst wall and daughter cysts that are surrounded by an echogenic debris, sometimes called hydatid sand, is frequently seen. On non-enhanced CT scans the multiple cysts appear mostly homogeneous and hypodense with no enhancement of the wall or cyst contents after con- trast administration.7,17 On MRI the hepatic cysts are char- acteristically of low image signal intensity on T1 and have very high signal intensity on T2-weighted images. No enhancement is seen of wall or cyst contents after injection of gadolinium chelates. Once again slight variations can occur in signal intensity due to intracystic haemor- rhage or infection. PCLD is most commonly a clini- cally benign condition and in most cases presents as vague upper abdom- inal discomfort or abnormal liver enzyme tests detected incidentally. There is often a positive family history or previous diagnosis of polycystic kidneys. In a large number of cases liver function tests remain normal. The disease usually occurs in older patients who often present with nodular liver enlargement and a nor- mal liver function test. When PCLD occurs in association with ADPKD the renal function may become CASE REPORTS 36 SA JOURNAL OF RADIOLOGY • August 2004 Fig. 3d. MRI confirming multiple smaller cysts in both kidneys. abnormal. In rare cases cysts may become massively enlarged or may become infected. Even rarer complications are Budd-Chiari syndrome, portal hyper- tension, or liver failure but these may be so severe that liver transplantation may be indicated.4,18 Treatment initially consists of treating symptomatic cysts, which are usually the largest cysts imaged, with unroofing, excision or hepatic resec- tion.16 In PCLD it is, however, advis- able to treat the symptomatic cyst with injection of 25 - 30% of the aspi- rated cyst volume using 99% ethanol, with re-aspiration after 20 minutes.16 Sonography is usually the most accu- rate imaging method for evaluation and treatment of symptomatic cysts under ultrasound-guided aspiration and ethanol injection.16 Arterial embolisation of liver disease repre- sents a new and exciting development in the treatment of patients in poor physical condition. In one case symp- tomatic relief was achieved as well as a reduction in hepatomegaly and ascites with improvement in physical condi- tion due to improved appetite.19 In summary, PCLD occurs as part of the manifestation of ADPKD in more than 50% of cases. Where the association occurs it is clinically rele- vant as the patient will much more likely suffer renal complications, with the liver disease running a relatively benign course. Radiologically, it must be distinguished from other cystic dis- eases of the liver. The most common of these are multiple metastases, hydatid disease, acquired cysts from trauma or infection and biliary cyst- adenoma.8 Radiological investigations play a crucial role in suggesting and con- firming the correct diagnosis and managing patients appropriately. References 1. Gabow PA. Autosomal dominant polycystic kidney disease. N Engl J Med 1993; 329: 332- 342. 2. D'Agata ID, Jonas MM, Perez-Atayde AR, Guay-Woodford LM. Combined cystic disease of the liver and kidney. Semin Liver Dis 1994; 14: 215-228. 3. Rizk D, Chapman AB. Cystic and inherited kid- ney diseases. Am J Kidney Dis 2003; 42: 1305- 1317. 4. Sherlock SA, Dooley J. Diseases of the Liver and Biliary System. 11th ed. Oxford: Blackwell Science, 2002: 584-586. 5. Feldman M, Friedman LS, Sleisenger MH. Sleisenger & Fordtran's Gastrointestinal and Liver Disease. 7th ed. Philadelphia: WB Saunders, 2002: 1596-1597. 6. Karhunen PJ, Tenhu M. Adult polycystic liver and kidney diseases are separate entities. Clin Genet 1986; 30(1): 29-37. 7. Mortele KJ, Ros PR. Imaging of diffuse liver dis- ease. Semin Liver Dis 2001; 21: 195-212. 8. Ralls PW, Jeffrey RB Jr, Kane RA, Robbin M. Ultrasonography. Gastroenterol Clin North Am 2002; 31: 801-825. 9. Lai EC, Wong J. Symptomatic nonparasitic cysts of the liver. World J Surg 1990; 14: 452-456. 10. Summerfield JA, Nagafuchi Y, Sherlock S, Cadafalch J, Scheuer PJ. Hepatobiliary fibropolycystic diseases. 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Proc Natl Acad Sci USA 1997; 94: 6397-6402. 16. Tikkakoski T, Makela JT, Leinonen S, et al. Treatment of symptomatic congenital hepatic cysts with single-session percutaneous drainage and ethanol sclerosis: technique and outcome. J Vasc Interv Radiol 1996; 7: 235-239. 17. Murphy BJ, Casillas J, Ros PR, Morillo G, Albores-Saavedra J, Rolfes DB. The CT appear- ance of cystic masses of the liver. Radiographics 1989; 9: 307-322. 18. Uddin W, Ramage JK, Portmann B, et al. Hepatic venous outflow obstruction in patients with polycystic liver disease: pathogenesis and treatment. Gut 1995; 36: 142-145. 19. Ubara Y, Takei R, Hoshino J, et al. Intravascular embolization therapy in a patient with an enlarged polycystic liver. Am J Kidney Dis 2004; 43: 733-738. CASE REPORTS 37 SA JOURNAL OF RADIOLOGY • August 2004