Chapter 18- Intrahepatic Biliary Tract Disease: ANOMALIES OF THE BILIARY TREES (INCLUDING LIVER CYSTS) Flashcards
What is ANOMALIES OF THE BILIARY TREES (INCLUDING LIVER CYSTS)?
A heterogeneous group of lesions exist in which the primary abnormality is altered architecture or paucity of the intrahepatic biliary tree.
Lesions may be found incidentally during radiographic
studies, surgery, or at autopsy.
Such conditions may become manifest as hepatosplenomegaly and portal hypertension in the absence of hepatic dysfunction, starting in late childhood or adolescence.
What are the five distinct conditions of ANOMALIES OF THE BILIARY TREES (INCLUDING LIVER CYSTS)?
- von Meyenburg complexes,
- polycystic liver disease,
- congenital hepatic fibrosis,
- Caroli disease, and
- Alagille syndrome
What is Von Meyenburg Complexes?
These are small clusters of modestly dilated bile ducts embedded in a fibrous, sometimes hyalinized, stroma located close to or within portal tracts.
These lesions are often referred to as
“bile duct hamartomas” ( Fig. 18-33 ).
Von Meyenburg complexes are common and without
clinical significance except in the differential diagnosis of metastases to the liver.
FIGURE 18-33 Bile duct hamartoma (von Meyenburg complexes).
Note the dilated and
irregularly shaped bile ducts.
What is Polycystic Liver Disease?
In this disease there are multiple diffuse cystic lesions in the liver, varying in number from a scattered few to hundreds ( Fig. 18-34 ).
The cysts, lined by cuboidal or flattened biliary
epithelium, contain straw-colored fluid.
FIGURE 18-34 Polycystic liver disease.
What is Congenital Hepatic Fibrosis?
In this condition portal tracts are enlarged by irregular, broad bands of collagenous tissue, forming septa that divide the liver into irregular islands.
Variable numbers of abnormally shaped
bile ducts are embedded in the fibrous tissue, and are in continuity with the biliary tree.
This anomaly arises because of persistence of the embryonic form of the biliary tree, with ensuing
portal tract fibrosis over the individual’s lifetime. Although individuals with congenital hepatic
fibrosis rarely develop cirrhosis, they may still face complications of portal hypertension,
particularly bleeding varices.
What is Congenital Hepatic Fibrosis?
In this condition portal tracts are enlarged by irregular, broad bands of collagenous tissue, forming septa that divide the liver into irregular islands.
Variable numbers of abnormally shaped
bile ducts are embedded in the fibrous tissue, and are in continuity with the biliary tree.
This anomaly arises because of persistence of the embryonic form of the biliary tree, with ensuing
portal tract fibrosis over the individual’s lifetime.
Although individuals with congenital hepatic
fibrosis rarely develop cirrhosis, they may still face complications of portal hypertension,
particularly bleeding varices.
What is Caroli Disease.
In this disease the larger ducts of the intrahepatic biliary tree are segmentally dilated and may
contain inspissated bile.
Pure forms are rare; this disease is usually associated with portal tract fibrosis of the congenital hepatic fibrosis type.
The disease is frequently complicated by intrahepatic cholelithiasis (described later), cholangitis, hepatic abscesses, and portal hypertension.
Persons with Caroli disease and congenital hepatic fibrosis have an increased
risk of developing cholangiocarcinomas.
These four conditions are associated with what disease?
Von Meyenburg Complexes.
Polycystic Liver Disease
Congenital Hepatic Fibrosis
Caroli Disease
Each of the four conditions discussed above can be associated with polycystic kidney disease .
Single or multiple liver cysts are the most frequent extrarenal manifestation of autosomaldominant
polycystic kidney disease caused by a mutation in PKD1 ( Chapter 20 ), and occur in
75% to 90% of patients with this type of kidney disease. [60]
A form of polycystic liver disease
caused by mutations of the PRKCSH gene (which encodes a protein kinase C substrate 80K-H)
does not coexist with polycystic kidney disease. [61]
Congenital hepatic fibrosis is strongly
associated with the autosomal recessive form of polycystic kidney disease, which is caused by
mutations of the PKHD1 (polycystic kidney and hepatic disease) gene. [62]
The exact
pathogenesis of these biliary lesions and the basis of their association with polycystic kidney
disorders remain unclear.
What is Alagille Syndrome (Syndromatic Paucity of Bile Ducts; Arteriohepatic Dysplasia)?
This is a rare autosomal dominant multi-organ disorder, in which the liver pathology is
characterized by absence of bile ducts in portal tracts.
The syndrome is caused by mutations
or deletion of the gene encoding Jagged1, which is located on chromosome 20p.
Jagged1 is a cell surface protein that functions as a ligand for Notch receptors ( Chapter 3 ).
Mutations in Jagged can be detected in as many as 94% of individuals with a clinical diagnosis of Alagille
syndrome, and some of the remaining patients have mutations in the Notch 2 receptor. [63]
The Jagged1-Notch signaling pathway regulates cell fate and is involved in the development of the
organ systems affected in Alagille syndrome.
What are the five major clinical features: Alagille Syndrome (Syndromatic Paucity of Bile Ducts; Arteriohepatic Dysplasia)?
- chronic cholestasis,
- peripheral stenosis of the pulmonary artery,
- butterfly-like vertebral arch defects,
- an eye defect known as posterior embryotoxon, and
- a peculiar hypertelic facies.
Patients can survive into adulthood but are at risk for hepatic failure and hepatocellular
carcinoma.
