Polycystic Liver Disease: Pathophysiology, Diagnosis and Treatment

Abstract

Polycystic liver disease (PLD) is a clinical condition characterized by the presence of more than 10 cysts in the liver. It is a rare disease Of genetic etiology that presents as an isolated disease or assoc\iated with polycystic kidney disease. Ductal plate malformation, ciliary dysfunction, and changes in cell signaling are the main factors involved in its pathogenesis. Most patients with PLD are asymptomatic, but in 2-5% of cases the disease has disabling symptoms and a significant reduction in quality of life. The diagnosis is based on family history of hepatic and/or renal polycystic disease, clinical manifestations, patient age, and polycystic liver phenotype shown on imaging examinations. PLD treatment has evolved considerably in the last decades. Somatostatin analogues hold promise in controlling disease progression, but liver transplantation remains a unique curative treatment modality.

Heterozygosity of ALG9 in Association with Autosomal Dominant Polycystic Liver Disease

“…Gene identification may be facilitated by using the principle of the two-hit disease model [ 15 , 16 , 23 , 24 , 60 , 64 , 65 ]. This model proposes a second (somatic) variant and the resulting loss of heterozygosity as the mechanism underlying cyst formation [ 15 , 16 , 23 , 24 , 60 , 64 , 65 ]. Indeed, loss of heterozygosity has been shown for PRKCSH- and SEC63 -affected ADPLD individuals [ 60 , 64 , 65 ].…”

“…Other available treatment options, such as surgical fenestration or treatment with somatostatin analogues, are aimed at an individual cyst or total liver volume reduction, respectively [ 15 , 16 , 23 , 24 ].…”

Novel α-1,3-Glucosyltransferase Variants and Their Broad Clinical Polycystic Liver Disease Spectrum

“…The exact pathophysiology of liver cyst development remains elusive [ 2 , 3 , 8 , 9 , 10 , 11 ]. The genetic underpinnings of PLD suggest the presence of a primary pathogenic germline variant in a PLD gene, and a secondary pathogenic somatic variant [ 1 , 3 , 9 , 12 , 13 , 14 , 15 ].…”

“…The genetic underpinnings of PLD suggest the presence of a primary pathogenic germline variant in a PLD gene, and a secondary pathogenic somatic variant [ 1 , 3 , 9 , 12 , 13 , 14 , 15 ]. The consequences of these variants involve many molecular pathways, and a wide range of factors have been suggested including (but not limited to) cAMP, estrogen, primary cilia dysfunction, bile acid levels, cell–matrix remodeling, epigenetics, post-translational modifications, autophagy, and aberrant proteostasis [ 2 , 3 , 8 , 9 , 10 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. This range of factors has resulted in a large variety in the potential targets for therapeutic treatment [ 2 , 3 , 8 , 9 , 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

“…The exact pathophysiology of liver cyst development remains elusive [2,3,[8][9][10][11]. The genetic underpinnings of PLD suggest the presence of a primary pathogenic germline variant in a PLD gene, and a secondary pathogenic somatic variant [1,3,9,[12][13][14][15]. The consequences of these variants involve many molecular pathways, and a wide range of factors have been suggested including (but not limited to) cAMP, estrogen, primary cilia dysfunction, bile acid levels, cell-matrix remodeling, epigenetics, post-translational modifications, autophagy, and aberrant proteostasis [2,3,[8][9][10][16][17][18][19][20][21][22][23][24][25][26].…”