Scoping Review on Polycystic Liver Disease in PKD1/PKD2 Gene Carriers: Genetic Aspects, Pathophysiology, and Therapeutic Approaches

Abstract

Polycystic liver disease (PLD) comprises hereditary disorders characterized by the progressive cystic replacement of liver parenchyma, leading to variable degrees of hepatomegaly and potential liver dysfunction. Depending on the affected gene, it may appear as isolated autosomal dominant polycystic liver disease (ADPLD) or in association with renal cysts as autosomal dominant or recessive polycystic kidney disease (ADPKD/ARPKD). This scoping review analyzed the genetic, pathophysiological, and therapeutic aspects of PLD in PKD1 and PKD2 mutation carriers, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and including 29 relevant studies published between 2014 and 2024. Several included studies suggested an association between PKD1 and PKD2 mutations and differences in disease severity and hepatic cyst burden, confirming their central role in the molecular pathogenesis of PLD. Current therapeutic strategies primarily rely on somatostatin analogs, which have demonstrated benefits in reducing liver volume and symptom burden in selected patients, whereas mechanistic target of rapamycin (mTOR) inhibitors have shown variable and modest results and remain under continued investigation. Surgical interventions, such as cyst fenestration, hepatic resection, or transplantation, are reserved for advanced cases. Emerging therapies targeting molecular pathways and personalized approaches show promise for future clinical application. Advances in genetics and molecular biology have enhanced the understanding of hepatic cystogenesis and provide the basis for the development of precision treatments and standardized clinical management protocols for patients with PLD.