Isolated polycystic liver disease

Isolated polycystic liver disease (PCLD), also known as autosomal dominant polycystic liver disease (ADPLD), is a rare genetic condition characterized by the progressive development of multiple fluid-filled cysts throughout the liver. Unlike autosomal dominant polycystic kidney disease (ADPKD), which also features liver cysts, isolated PCLD occurs without significant kidney involvement. The cysts arise from biliary epithelium (cholangiocytes) and gradually increase in number and size over time, predominantly affecting women more severely than men, likely due to the influence of estrogen on cyst growth. Factors such as pregnancy, oral contraceptive use, and estrogen replacement therapy have been associated with more extensive cystic disease. The condition is caused by pathogenic variants in several genes, including PRKCSH (encoding hepatocystin), SEC63, LRP5, ALG8, ALG9, SEC61B, and GANAB. These genes are involved in protein processing, folding, and quality control within the endoplasmic reticulum. Most affected individuals remain asymptomatic for decades, with cysts typically becoming clinically apparent in adulthood. When symptoms occur, they are usually related to massive hepatomegaly (liver enlargement) and include abdominal distension, early satiety, dyspnea (shortness of breath), abdominal pain, and gastroesophageal reflux. Complications can include cyst infection, cyst hemorrhage, cyst rupture, and rarely portal hypertension or inferior vena cava compression. Treatment depends on symptom severity. Asymptomatic patients generally require monitoring only. For symptomatic patients, options include cyst aspiration with sclerotherapy, laparoscopic or open fenestration (surgical unroofing of cysts), and in severe cases, liver resection of the most affected segments. Somatostatin analogues such as lanreotide and octreotide have shown modest efficacy in reducing liver volume in clinical trials and represent an emerging medical therapy. Liver transplantation is reserved for patients with severely debilitating symptoms refractory to other interventions. Avoidance of exogenous estrogen is generally recommended for affected women.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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