Polycystic Liver Disease (PLD)/ Congenital Fibrosis

Structural Liver Disease

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Description

Polycystic liver disease (PLD) is characterized by the formation of fluid-filled cysts throughout the liver. It can occur as an isolated form in autosomal dominant polycystic liver disease (ADPLD), which was formerly abbreviated as polycystic liver disease (PCLD). It can also be present as an extra-renal manifestation in autosomal dominant polycystic kidney disease (ADPKD).

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Genetics

PLD is caused by mutations in the PRKCSH, SEC63, LRP5, SEC61B, ALG8 or PKHD1 gene in ADPLD, or in the PKD1, PKD2 or GANAB gene in ADPKD (Figure 1). All genetic mutations lead to reduced levels of functional polycystin-1. This ciliary protein is therefore considered to be the pivotal protein in the development of liver cysts.

Clinical presentation

The variation in PLD phenotype is broad. The majority of patients remain asymptomatic and might not even know that they are affected by the disease. However, persistent progression of cyst growth may lead to hepatomegaly with liver volumes ranging from 2 to 15 liters (normal: ~1.5 liter).

Risk factors

The size and number of hepatic cysts increase with age, and the disease typically becomes symptomatic in the fourth decade of life, which results in reduced quality of life.
Gender is the most defining risk factor associated with PLD severity. Although PLD has an autosomal dominant inheritance pattern, about 80% of patients in cohort studies are female. In addition, pre-menopausal use of estrogen-containing oral contraceptives, and post-menopausal use of hormonal replacement therapy with estrogens is associated with larger liver volumes. We stress that it is important to avoid any exogenous estrogen use in patients with PLD. The effect of progestins on PLD severity has not been investigated.

Symptoms

The growth and accumulation of cysts may cause hepatomegaly and compression of adjacent anatomical structures. Patient-reported symptoms include abdominal fullness, lack of appetite, early satiety, gastro-esophageal reflux, nausea, pain, dyspnea, limitations in mobility, fatigue, anxiety and unhappiness with appearance, particularly due to abdominal distension or herniation of the abdominal wall.

Diagnosis

PLD is diagnosed through imaging with either ultrasound, CT or MRI.

Management

Treatment of hepatomegaly and large hepatic cysts should only be considered in case of symptomatic disease. For clinical guidance on decision making we refer to the following articles:
- “Clinical management of polycystic liver disease.” Van Aerts et al. (2018)
- “Treatment of polycystic liver disease. Update on the management” Aussilhou et al. (2018)
- “Diagnosis and management of polycystic liver disease.” Gevers et al. (2013)
- “Medical and surgical treatment options for polycystic liver disease.” Drenth et al. (2010)

Treatment options include:
- Aspiration sclerotherapy
- Laparoscopic fenestration
- Liver resection
- Liver transplantation
- Somatostatin analogues
- Complications of PLD

Important complications that can arise in PLD patients are:
- Hepatic cyst infections
- Portal hypertension and ascites
- Hepatic cyst rupture occurs very rarely, and can be caused by trauma or occur spontaneously. Patients can present with severe abdominal pain and hemodynamic instability.

CPMS

If you wish to discuss a PLD patient with experts from the ERN, you can upload cases to the CPMS.
The CPMS is essential for interaction between healthcare professionals and experts on clinical decision making, and was provided by the European Union to all ERNs. CPMS supports online multidisciplinary meetings (tele-boards) to discuss patients with diagnostic or therapeutic dilemmas in need of expert consultation. CPMS offers the opportunity to upload and share clinical data of patients and pictures such as histological slides or MRI images. Importantly, this is fully in line with European data protection law. It is obligatory to inform patients about CPMS and obtain their informed consent before their data are entered into the system (see CPMS Privacy Statement published by the European Commission on 14 December 2017). The consent form is available in all EU languages in the CPMS system.

Media

Figure 1: Schematic representation of the localization and function of proteins encoded by the genes involved in polycystic liver disease. ALG8, a-1,3-glucosyltransferase; Ca2þ, calcium; ER, endoplasmic reticulum; FC, fibrocystin/polyductin; GIIa, glucosidase II subunit a; GIIb, glucosidase II subunit b; LRP5, LDL receptor related protein 5; PC1, polycystin-1; PC2, polycystin-2; SEC61b, protein transport protein Sec61 subunit b; SEC63, translocation protein SEC63 homolog (© Lee-Law et al.).
Figure 1: Schematic representation of the localization and function of proteins encoded by the genes involved in polycystic liver disease. ALG8, a-1,3-glucosyltransferase; Ca2þ, calcium; ER, endoplasmic reticulum; FC, fibrocystin/polyductin; GIIa, glucosidase II subunit a; GIIb, glucosidase II subunit b; LRP5, LDL receptor related protein 5; PC1, polycystin-1; PC2, polycystin-2; SEC61b, protein transport protein Sec61 subunit b; SEC63, translocation protein SEC63 homolog (© Lee-Law et al.).

More information

Patient information with downloadable leaflets and information videos ERN Webinar on cyst infection Our partner, Radboud UMC has kindly provided us with a number of information videos, click here for the playlist ERN Webinar on the new EASL Clinical Practice Guidelines on the management of cystic liver diseases (2022)

Clinical practice guidelines

Please click here to view clinical practice guidelines for the diseases covered by ERN RARE-LIVER.