Congenital cystic lesions of the biliary tree

Fibropolycystic liver diseases (FPLDs) encompass a heterogeneous group of rare, congenital disorders of the biliary tree deriving from an abnormal embryogenesis of the primordial ductal plate caused by a genetically determined dysfunction of morphogenetic proteins expressed in the primary cilia of cholangiocytes ("ciliopathies"). Among this group, it is important to notice three different clusters of disease: polycystic liver diseases (PLDs), fibrocystic liver diseases (FLDs), and choledochal cysts (CCs). PLDs are characterized by the development of multiple (>20) fluid-filled biliary cysts widespread throughout liver parenchyma and disconnected from biliary tree. The natural history of PLDs is characterized by growth of cyst during adult age, leading to debilitating hepatomegaly. The ductal dysgenesis may affect, in FLDs, the biliary system at multiple levels, from the small intrahepatic bile ducts (congenital hepatic fibrosis) to the larger intrahepatic bile ducts (Caroli's disease or Caroli's syndrome, when Caroli's disease coexists with congenital hepatic fibrosis), leading to biliary microhamartomas and segmental bile duct dilations, accompanied by progressive fibrogenesis. These fundamental lesions are the hallmark of FLDs and are responsible for the major complications, such as portal hypertension, cholestasis, recurrent cholangitis, sepsis, and cholangiocarcinoma. CCs are congenital alterations resulting from ductal plate malformation, involving the largest intra or extrahepatic bile ducts that mainly affect a paediatric population. Early surgical intervention is pivotal to avoid complications related to obstructive frame, ab extrinseco compression, rupture or malignant evolution. FPLDs often associate with a spectrum of disorders affecting many organs, primarily the kidney, and thus they are collectively termed hepatorenal fibrocystic disease (HRFCD). Among them, the autosomal-dominant and recessive polycystic kidney disease (ARPKD) is the most frequently associated disease, respectively to PLD and CHF, and the renal function impairment is central in disease progression. Since FPLDs are still orphan diseases, liver transplantation represents the only curative approach in advanced cases. Recent experimental evidence supports the strong translational relevance of these diseases as models for understanding the mechanisms of liver repair and unveiling potential therapeutic targets.