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Last updated: 03/31/2023
Years published: 1989, 1990, 1996, 1998, 2005, 2018, 2023
NORD gratefully acknowledges Etienne Leveille, MD, and Joost PH Drenth, MD, PhD, Professor of Gastroenterology and Hepatology, Head, Department of Gastroenterology and Hepatology, Radboud UMC, and Dr. Lucas Bernts, Radboud UMC, The Netherlands, for assistance in the preparation of this report.
Summary
Polycystic liver disease, also called autosomal dominant polycystic liver disease (ADPLD) is an inherited disorder estimated to affect less than 1 in 10,000 people. It is characterized by the progressive growth of cysts of various sizes scattered throughout the liver. People affected by this condition tend to have more and larger cysts as they age and usually start to have symptoms as early as age 30. However, many affected individuals do not have symptoms. Enlargement of the liver (hepatomegaly) can cause abdominal pain and discomfort, shortness of breath (dyspnea), early satiety and gastro-esophageal reflux. Rare complications are hepatic cyst hemorrhage, infection or rupture. Surgical and medical treatment is available to manage the symptoms, but the only definitive treatment for this condition is liver transplant. Most cases are inherited in an autosomal dominant pattern, but some occur in families with no family history of the condition. Sometimes, cysts are found in the liver in association with ADPKD. In fact, most people who have ADPKD have liver cysts.
Polycystic liver disease is characterized by the growth of more than 10 cysts in the liver, ranging in size from a few millimeters to over 15 cm in diameter. Symptoms usually begin to show in the third decade, as cysts grow and increase in number with age. Some people begin to have symptoms in early adulthood, but many affected individuals do not have symptoms. The growth and accumulation of cysts can cause enlargement of the liver (hepatomegaly) and compression of adjacent anatomical structures, leading to abdominal pain and discomfort, shortness of breath (dyspnea), indigestion (dyspepsia), gastro-esophageal reflux and limited mobility. More rarely, liver cysts can also compress the bile duct and lead to yellowing of the skin (jaundice). Compression of the blood vessels of the liver by cysts can lead to accumulation of fluid in the abdomen (ascites), bleeding and high blood pressure in the blood flow from intestines to the liver (portal hypertension). In rare cases, patients can suffer from cyst bleeding (hepatic cyst hemorrhage) or a cyst can be infected by bacteria (hepatic cyst infection), causing pain and fever. Infrequently, large liver cysts may rupture, causing severe abdominal pain. Even with the presence of many cysts, the liver of individuals with polycystic liver disease functions normally.
Changes (mutations or pathogenic variants) in many different genes can cause ADPLD. Mutations in PRKCSH cause about 20% of cases and mutations in SEC6 cause about 15% of cases. Other genes associated with ADPLD include ALG8, GANAB, LRP5, PKHD and SEC61B3. However, less than 50% of individuals with polycystic liver disease have a mutation in one of these genes, so other genes may be involved in this condition.
Pathogenic variants in SEC63 and PRKCSH lead to defects in processing, folding and translocation of newly synthesized glycoproteins. This is associated with embryological malformations which contributes to the formation of fluid-filled cysts throughout the liver.
Most cases of polycystic liver disease are inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
Polycystic liver disease is estimated to affect less than 1 in 10,000 people. This is likely an underestimate because many people with the condition do not have symptoms. Males and females are affected in equal numbers, but most patients with symptoms and with severe disease are women. The suggested cause of this difference is that female sex hormones, such as estrogen, contribute to growth of liver cysts. Oral contraceptives and estrogen replacement therapy are also associated with more severe disease]. Cysts can begin to grow at any age but are rare in childhood and more common with age. The age at which symptoms begin to occur varies with individuals but is usually after 30 years old.
Magnetic resonance imaging (MRI) computed tomography (CT) scan and ultrasound (US) are used to take pictures of the liver to see if cysts are present. The images are used for diagnosis and monitoring of cysts growth. Molecular genetic testing is available to look for mutations in the SEC63, LRP5 and PRKCSH genes and may be particularly helpful in individuals that inherited the disease from one of their parents. It is also possible to test for blood levels of two markers of liver and bile duct disease: gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP). These two markers might be elevated in patients with severe polycystic liver disease.
Treatment
Treatment may not be necessary in many cases of polycystic liver disease and is only indicated in severely affected or symptomatic patients. Large cysts (>5 cm) can be treated with aspiration sclerotherapy, which includes puncture of the cyst, removal of the fluid and treatment of the cyst wall with a chemical allowing tissues to harden, (sclerosing agent) such as ethanol. When multiple large cysts are causing symptoms, keyhole surgery can be a treatment option. The surgeon punctures and then removes the โroofโ of the cysts. This procedure is called laparoscopic fenestration. It is also possible to remove parts of the liver (hepatic resection) to reduce symptoms related to hepatomegaly. The only definitive treatment of PLD, used in only the most severe cases, is liver transplant.
Medication to slow down cyst growth and fluid secretion in the liver (somatostatin analogs, namely octreotide and lanreotide) is also useful in reducing liver volume. Because they are very expensive, these medications are typically reserved for patients with moderate to severe disease with reduced quality of life. Referral to a specialized center is recommended. As estrogen promotes cysts growth, it is recommended for women diagnosed with polycystic liver disease to stop hormonal contraceptives or estrogen replacement therapy.
Genetic counseling is recommended for patients and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Duijzer R, Barten TRM, Staring CB, Drenth JPH, Gevers TJG. Treatment of ppolycystic liver disease: impact on patient-reported symptom severity and health-related quality of life. J Clin Gastroenterol. 2022;Oct 1 56(9):731-739. doi: 10.1097/MCG.0000000000001749. Epub 2022 Aug 19. PMID: 35997709; PMCID: PMC9432811.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of cystic liver diseases. J Hepatol. 2022;Oct 77(4):1083-1108. doi: 10.1016/j.jhep.2022.06.002. Epub 2022 Jun 18. PMID: 35728731.
Olaizola P, Rodrigues PM, Caballero-Camino FJ, Izquierdo-Sanchez L, Aspichueta P, Bujanda L, Larusso NF, Drenth JPH, Perugorria MJ, Banales JM. Genetics, pathobiology and therapeutic opportunities of polycystic liver disease. Nat Rev Gastroenterol Hepatol. 2022; Sep19(9):585-604. doi: 10.1038/s41575-022-00617-7. Epub 2022 May 13. PMID: 35562534.
Suwabe T, Chamberlain AM, Killian JM, King BF, Gregory AV, Madsen CD, et al. Epidemiology of autosomal-dominant polycystic liver disease in Olmsted county. JHEP Rep. 2020;2:100166. doi: 10.1016/j.jhepr.2020.100166
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Porath B, et al., Mutations in GANAB, Encoding the glucosidase IIalpha subunit, cause autosomal-dominant polycystic kidney and liver disease. Am J Hum Genet. 2016;98(6):1193-1207.
Hogan MC, et al., Liver involvement in early autosomal-dominant polycystic kidney disease. Clin Gastroenterol Hepatol. 2015;13(1):155-64 e6.
Cnossen WR Drenth JP. Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management. Orphanet J Rare Dis. 2014 9:69.
Cnossen WR, et al., Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis. Proc Natl Acad Sci USA. 2014;111(14):5343-8.
Leao RN, Salustio R, and Ribeiro JV. Polycystic liver disease. BMJ Case Rep. 2014.
Perugorria MJ, et al., Polycystic liver diseases: advanced insights into the molecular mechanisms. Nat Rev Gastroenterol Hepatol. 2014;11(12):750-61.
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Bakoyiannis A, et al., Rare cystic liver lesions: a diagnostic and managing challenge. World J Gastroenterol. 2013;19(43):7603-19.
Gevers TJ and Drenth JP. Diagnosis and management of polycystic liver disease. Nat Rev Gastroenterol Hepatol. 2013;10(2):101-8.
Long-Xian Z, et al., Treatment of polycystic liver disease: a hypothesis, patient characteristics, short and long-term results. Ann Hepatol. 2013;12(5):782-90.
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Van Keimpema L, et al., Patients with isolated polycystic liver disease referred to liver centres: clinical characterization of 137 cases. Liver Int. 2011;31(1):92-8.
Drenth JP, et al., Medical and surgical treatment options for polycystic liver disease. Hepatology. 2010;52(6):2223-30.
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Hoevenaren IA, et al., Polycystic liver: clinical characteristics of patients with isolated polycystic liver disease compared with patients with polycystic liver and autosomal dominant polycystic kidney disease. Liver Int. 2008;28(2):264-70.
Delis SG, et al., Rare localizations of the hydatid disease. Experience from a single center. J Gastrointest Surg. 2007;11(2):195-8.
Alvaro D, et al., Estrogens and the pathophysiology of the biliary tree. World J Gastroenterol. 2006;12(22):3537-45.
Davila S, et al., Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat Genet. 2004;36(6):575-7.
Sayek I, Tirnaksiz MB and Dogan R. Cystic hydatid disease: current trends in diagnosis and management. Surg Today. 2004;34(12):987-96.
Li A, et al., Mutations in PRKCSH cause isolated autosomal dominant polycystic liver disease. Am J Hum Genet. 2003;72(3):691-703.
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