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Discussion

Polycystic Liver Disease (PLD) can either exist as an isolated disease that is sporadic or dominantly inherited, or more commonly, is related to Adult Polycystic Kidney Disease (APKD). APKD is a systemic disorder characterized by cystic involvement of the kidneys, liver, pancreas, seminal vesicles, and meninges. APKD is inherited as an autosomal dominant trait (ADPKD) or an autosomal recessive trait (ARPKD). PLD in association with ARPKD presents in childhood with severe renal disease that is often fatal at a young age. More commonly, PLD presents in adulthood and in association with ADPKD. ADPKD is a common disease with an incidence of 1/500 to 1/1000 patients. Although ADPKD is fully penetrant, the phenotype is variable and the prevalence of extrarenal manifestations including hepatic cysts varies widely. PLD that is related to ADPKD is linked to either PKD1 (the main gene locus responsible for APKD) or PKD2 germline mutations. The genetic mechanisms are not completely understood but involve a two-hit tumor suppressor model of focal cyst formation.

In ADPKD, hepatic cysts generally develop later than renal cysts and increase in frequency with age. The prevalence of liver cysts in ADPKD increases from 20% in the third decade to nearly 70% in the seventh decade (compared to 4% in 70yr olds in the general population). Approximately one fourth of ADPKD patients will not develop liver cysts. Hepatic cystic involvement is more common in women, and women have larger and more numerous cysts compared to men. In addition, previous pregnancies and the use of estrogen may be associated with an increased number of hepatic cysts and increased cyst volume. Only a minority of APKD patients develop massive liver involvement with symptoms, most of which are women. A review of 37 ADPKD patients with massive hepatomegaly in 1997 by Chauveau et al showed that 35 of the 37 patients were female and that renal involvement in these patients was extremely heterogenous.

The pathogenesis of PLD is based on an abnormality of remodeling of the ductal plate. Liver cysts in ADPKD arise from two different structures. Intrahepatic cysts arise from biliary microhamartomas which are overgrowth of bile ductules. As the cyst grows, it becomes disconnected from the bile ducts but retains the single layer of cuboidal bile duct epithelium. The epithelium of the cyst wall is supported by an underlying basement membrane and a surrounding rim of fibrous stroma. These cysts are typically located peripherally in the liver and may grow up to 10cm in size. Adjacent liver tissue is typically normal. Hepatic cysts may also arise from peribiliary glands that surround intrahepatic bile ducts. These glands undergo cystic dilatation however, they tend to be smaller in size and located in the hepatic hilum or in the area surrounding a larger portal tract.

Hepatic cysts in ADPKD are usually asymptomatic and rarely cause liver failure. Consequently, symptoms of PLD typically indicate a complication or mass effect of a large cyst. Complications of a singe cyst include infection, rupture, hemorrhage, or torsion. Abdominal pain and fever may suggest an underlying cyst infection. Approximately half of cyst infections are noscomial, related to cyst aspiration however, patients are at risk for spontaneous infections as well, especially those patients who are on chronic hemodialysis. Hemorrhage into a cyst may present with abdominal pain and fever and as a result, may be misdiagnosed as cyst infection or cholecystitis. MRI can accurately distinguish hemorrhage from other cyst complications as the former will be associated with a hypertense signal on T1 and T2 images and a fluid-fluid level. Ruptured hepatic cysts often present as an acute abdomen with ascites.

Complications of multiple cysts include ascites from hepatic venous outflow obstruction, portal hypertension with variceal bleeding, inferior vena cava obstruction, and bile duct compression resulting in jaundice. Chronic symptoms of massive polycystic liver include abdominal fullness, distension, and pain. Mechanical compression by large cysts may present as early satiety, dyspnea, abdominal hernias, or uterine prolapse.

Unlike the progressive deterioration of renal function in ADPKD, hepatic function remains relatively stable due to preservation of the liver parenchyma. In massive PLD, up to one half of patients will have abnormal alkaline phosphatase and gamma-glutamyl transferase. Less than 20% of patients will have elevated aminotransferase or bilirubin levels. Jaundice secondary to bile duct compression in the porta hepatis is rare.

Ultrasound is the most accurate technique for diagnosing the cystic nature of a hepatic lesion. An uncomplicated cyst on ultrasound will present as an anechoic mass with smooth borders, no perceptible wall, and no septations. Cysts complicated by hemorrhage or infection may show septations or cyst debris. On CT, hepatic cysts are homogeneous and hypodense and show no enhancement following administration of contrast dye. Strands of increased density that represents the normal residual hepatic parenchyma surround the visualized cysts. On MRI, hepatic cysts will appear as a low signal on T1 weighted images and as a high signal of T2 weighted images.

There are several options for the treatment of PLD including cyst aspiration, cyst fenestraton, vascular stenting, liver resection, and liver transplantation. Cyst aspiration is recommended for symptoms caused by one or few dominant cysts. Frequent reaccumulation of cystic fluid after cyst aspiration requires that percutaneous aspiration always be combined with sclerotherapy using either alcohol or minocycline. Prior to injection with a sclerosing agent, contrast should be injected into the cyst to exclude communication between the cyst and the biliary tree. Aspiration with sclerotherapy results in sustained improvement in only 50% of cases. The success rate inversely correlates with cyst size. Complications include cyst infection and peritoneal or biliary leak of alcohol.

Resection or fenestration of hepatic cysts is used for treatment of symptomatic superficial cysts that have a portion of their wall accessible for cyst unroofing. Large cysts that are positioned anterior, lateral, or superior to liver parenchyma are optimal for cyst fenestration. After the cyst has been unroofed, cyst fluid is secreted into the peritoneal cavity and reabsorbed. Although fenestration is considered a low risk procedure, complications occur in 23-57% of cases. Complications of cyst fenestration include persistent ascites (especially in those patients with renal failure) and vascular or bile duct injury. Relief of symptoms is usually achieved initially; however, cyst recurrence is common. A laparoscopic approach is recommended in patients with cysts that are located in the anterior segments of the liver in order to reduce adhesions and to allow for repeated treatments. Open fenestration should be reserved for patients with multiple small cysts that are distributed throughout the liver, including posterior liver segments.

Percutaneous portal venous stenting and transhepatic portosystemic shunt has been used to reestablish flow and reduce pressure gradients in patients with portal or caval obstruction due to cyst compression. These techniques are often reserved for nonsurgical candidates with complications of portal obstruction such as variceal bleeding and ascites.

Liver resection as a treatment for PLD is often combined with cyst fenestration and subsequent fulguration of open cystic cavities using electrocautery or argon-beam coagulation. Symptomatic patients with small numerous cysts respond better to liver resection compared to individual cyst fenestration. Mortality has been reported to be as high as 42% and morbidity up to 84%. Complications of resection include ascites, biliary leak, infection, and pancreatitis. Despite early complications, most patients achieve sustained symptom improvement and cyst resolution.

Liver transplantation is rarely used for treatment of PLD as patients typically present with preserved hepatic function. Isolated liver transplantation is considered in patients with symptomatic diffuse cystic involvement in whom resection has failed or in patients with severely affected liver parenchyma and hepatic insufficiency. Combined liver/kidney transplant is performed in patients with PLD who have severe renal dysfunction due to cystic disease. Medical treatment includes avoidance of estrogens and proton pump inhibitors for symptomatic relief. Somatostatin analogues and estrogen antagonists have not been shown to be beneficial in reducing cyst size.