Polycystic liver diseases: Genetics, mechanisms, and therapies

Polycystic liver disease (PLD), a genetic cholangiociliopathy, is characterized by the presence of multiple liver cysts of different shape and size filled with cystic fluid. This chapter discusses the knowledge related to the genetics of PLD, the mechanisms involved, and potential therapeutic targets identified. PLD exists as an extra-renal manifestation of autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease or as isolated autosomal dominant PLD. Considerable progress in understanding of the genetic landscape in PLD and identification of dysregulated signaling pathways and abnormal cellular functions of hepatic cystogenesis facilitated the discovery of multiple potential therapeutic targets for disease treatment. The chapter also discusses promising monotherapies and combinational therapies in PLD treatment. Mounting evidence suggests that drug combinations might be more effective that monotherapies in PLD treatment. In PLD, a dysregulated mammalian target of rapamycin signaling network contributes to disease progression by affecting a spectrum of intracellular pathways, including growth factor signaling.