Polycystic
liver diseases (
PLD) are a group of
genetic disorders initiated by mutations in several
PLD-related genes and characterized by the presence of multiple cholangiocyte-derived hepatic
cysts that progressively replace liver tissue.
PLD co-exists with
Autosomal Dominant Polycystic Kidney Disease (
ADPKD) and Autosomal Recessive PKD as well as occurs alone (i.e., Autosomal Dominant
Polycystic Liver Disease [ADPLD]).
PLD associated with
ADPKD and
ARPKD belong to a group of disorders known as cholangiociliopathies since many disease-causative and disease-related
proteins are expressed in primary cilia of cholangiocytes. Aberrant expression of these
proteins in primary cilia affects their structures and functions promoting cystogenesis. Current medical
therapies for
PLD include symptomatic management and surgical interventions. To date, the only available drug treatment for
PLD patients that halt
disease progression and improve quality of life are
somatostatin analogs. However, the modest clinical benefits, need for long-term maintenance
therapy, and the high cost of treatment justify the necessity for more effective treatment options. Substantial evidence suggests that experimental manipulations with components of the signaling pathways that influence
cyst development (e.g., cAMP, intracellular
calcium,
receptor tyrosine kinase,
transient receptor potential cation channel subfamily V member 4 (TRPV4) channel, mechanistic target of
rapamycin (mTOR),
histone deacetylase (HDAC6),
Cdc25A phosphatase,
miRNAs and
metalloproteinases) attenuate growth of hepatic
cysts. Many of these targets have been evaluated in pre-clinical trials suggesting their value as potential new
therapies. This review outlines the current clinical and preclinical treatment strategies for
PLD.