Clinical profile of autosomal dominant polycystic liver disease

Abstract

Most reports on the natural history, manifestations, and treatment of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The purpose of this study was to develop a clinical profile of isolated autosomal dominant polycystic liver disease (ADPLD) using nonaffected family members as controls. The study included 146 probands, known affected relatives, and first-degree relatives of affected individuals. Participants underwent a formalized medical history interview and physical examination, ultrasonographic examination of the liver and kidneys, magnetic resonance angiography of the brain, and echocardiography. Thirty-eight of the 49 individuals diagnosed with polycystic liver disease before participation in the study were or had been symptomatic. Of 97 previously undiagnosed at-risk individuals, 23 were affected, 39 were unaffected, and 35 were indeterminate. Compared with patients with a negative or indeterminate diagnosis, those with polycystic liver disease had slightly higher levels of serum alkaline phosphatase and total bilirubin and lower levels of total cholesterol and triglycerides. Female patients had a significantly higher mean cyst score than male patients. The cysts were found to arise from the dilatation of biliary microhamartomas and from peribiliary glands. Structural mitral leaflet abnormalities were detected more frequently in affected than in indeterminate or nonaffected individuals. A vascular phenotype was detected in 5.6% of the patients with isolated ADPLD diagnosed clinically and/or by linkage analysis but in none of the unaffected patients. In conclusion, isolated ADPLD is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis, manifestations, and management. (HEPATOLOGY 2003;37:164-171.)

Medical and surgical treatment options for polycystic liver disease1

“…These complexes can grow into cysts in adult life and become disconnected as they grow from von Meyenburg complexes. [14][15][16] Probably, abnormalities in biliary cell proliferation and apoptosis and enhanced fluid secretion are key elements in the pathogenesis of PLD. In cystic livers, activation of several signal transduction pathways is altered leading to hyperproliferation and hypersecretion.…”

Magnetic Resonance Imaging Evaluation of Hepatic Cysts in Early Autosomal-Dominant Polycystic Kidney Disease

“…The natural history of hepatic cysts in patients with ADPKD (2,6,9 -16) or isolated autosomal-dominant polycystic liver disease (12) has been studied extensively. Many of these studies focused on the prevalence of hepatic cysts associated with age, gender, and various clinical parameters such as renal function and hypertension (2,6,9 -12).…”

Disrupted cell adhesion but not proliferation mediates cyst formation in polycystic liver disease

“…47 This is significant as hepatic cyst growth is promoted by estrogen supplementation and pregnancies. 1,50,51 Nevertheless, we did not find overexpression of ERa in PCLD tissues (data not shown). This suggests Figure 3 Immunohistochemical staining of adhesion molecules in control and PCLD liver.…”

“…1 So far, two genes, PRKCSH and SEC63, have been linked to PCLD by genomewide linkage analyses and extensive sequencing. 2,3 The incriminated proteins, hepatocystin and Sec63p, respectively, are predicted to have their function in the glycosylation and transport of glycoproteins into and out of the endoplasmic reticulum (ER) (reviewed in Drenth et al 4 ).…”