Isolated Polycystic Liver Disease

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

SEC63, PRKCSH, LRP5, ALG8, ALG9, PKD2, PKHD1, PKD1, GANAB, TMEM216, MKS1, WDPCP, TMEM231, CEP55, RPGRIP1L, RPGRIP1, B9D1, TCTN2, CSPP1, CEP290, B9D2, TMEM107, FBN1, TMEM67, CC2D2A, SST, GPBAR1, SIL1, NXN, CDC25A

Drugs

Menadione sodium bisulfite, Sodium ascorbate and menadione sodium bisulfite

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Isolated polycystic liver disease (PCLD) is a genetic disorder characterized by the appearance of numerous cysts spread throughout the liver and that in most cases is described as autosomal dominant polycystic liver disease (ADPCLD).

Epidemiology

The prevalence of ADPCLD is 1/100, 000.

Clinical description

Women are predominantly affected and have a larger number of cysts than affected males. Cysts are undetectable early in life and usually appear after the age of 40 years. Their number and size increases with age. Symptoms depend on the mass (compression effect) and can include abdominal distension, gastro-esophageal reflux, early satiety, dyspnea, decreased mobility and back pain due to hepatomegaly. Some patients are asymptomatic. Other complications (intracystic hemorrhage or infection, torsion or rupture of cysts) can cause acute abdominal pain. Liver function is usually normal. There is no portal hypertension. Extrahepatic manifestations are very rare and may include intracranial aneurysms (usually small sized and at a low risk of rupture) and mitral leaflet abnormalities. In rare cases hepatomegaly can lead to malnutrition which can be lethal.

Etiology

Liver cysts result from overgrowth of biliary epithelium or from dilatation of peribiliary glands. Some cases occur sporadically, but most are inherited as an autosomal dominant trait (ADPCLD). ADPCLD is caused in 1/3-1/2 of cases by mutations in the PRKCSH or SEC63 genes. As not all cases of PCLD have a mutation in one of these genes, other not yet discovered genes and modes of transmission may exist.

Diagnostic methods

Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) is used for diagnosis. Among patients at risk (belonging to a family known to be affected), diagnostic criteria include more than one cyst in patients below the age of 40 years, and more than three cysts in those over 40. For patients with no known affected relatives, the usual criterion is more than 20 cysts.

Differential diagnosis

Differential diagnoses include multiple liver cysts, found in association with autosomal dominant polycystic kidney disease (ADPKD; see this term), but PCLD is genetically distinct from ADPKD with liver cysts. Simple liver cysts are also a differential diagnosis. Caroli disease (see this term), characterized by cysts communicating with the biliary tract, is differentiated by using imaging with contrast agents specifically excreted into the bile.

Management and treatment

Most patients are asymptomatic and do not require treatment. For those with symptoms, management depends on the extent, distribution, and anatomy of the cysts and may include percutaneous cyst aspiration, alcohol sclerosis, cyst fenestration, partial hepatectomy, and even liver transplantation (in rare cases where the massively enlarged liver considerably alters the quality of life). Any form of estrogen therapy should be stopped immediately. Recently, lanreotide and long acting octreotide (somatostatin analogues) have been shown to be safe and effective treatments for PCLD that reduce moderate polycystic liver volume and prevent its growth.

Prognosis

Most patients with PCLD have good prognosis and do not require treatment.