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Cystic Diseases of the Biliary Tract and Liver
Cystic lesions of liver may be initially recognized during infancy and childhood. Hepatic fibrosis can also occur as part of an associated developmental defect ( Table 392.1 ). Cystic renal disease is usually associated and often determines the clinical presentation and prognosis. Virtually all proteins encoded by genes mutated in combined cystic diseases of the liver and kidney are at least partially localized to primary cilia in renal tubular cells and cholangiocytes.
Table 392.1
Syndromes Associated With Congenital Hepatic Fibrosis
| DISORDER | ASSOCIATED FEATURES |
|---|---|
| Autosomal recessive polycystic kidney disease | Ductal plate malformation, Caroli syndrome |
| Autosomal dominant polycystic kidney disease | Ductal plate malformation, Caroli syndrome |
| Autosomal dominant polycystic liver disease | Rarely, congestive heart failure |
| Jeune syndrome | Asphyxiating thoracic dystrophy, with cystic renal tubular dysplasia, Caroli syndrome |
| Joubert syndrome | Central nervous system defects, cardiac malformations |
| COACH syndrome | C erebellar vermis hypoplasia, o ligophrenia, congenital a taxia, ocular c oloboma, h epatic fibrosis |
| Meckel-Gruber syndrome | Cystic renal dysplasia, abnormal bile duct development with fibrosis, posterior encephalocele, polydactyly |
| Carbohydrate-deficient glycoprotein syndrome type 1b | Phosphomannose isomerase 1 deficiency chronic diarrhea, protein-losing enteropathy |
| Ivemark syndrome type 2 | Autosomal-recessive renal-hepatic-pancreatic dysplasia |
| Nephronophthisis type 3 | Tapetoretinal degeneration |
| Bardet-Biedl syndrome | Retinal degeneration, obesity, limb deformities, hypogonadism |
| Oral-facial-digital syndrome type 1 | Oral clefts, hamartomas or cysts of the tongue, digital anomalies pancreatic cysts |
| Miscellaneous syndromes | Intestinal lymphangiectasia, enterocolitis, cystic short rib (Beemer-Langer) syndrome, osteochondrodysplasia |
After Suchy FJ, Sokol RJ, Balistreri WF, editors: Liver disease in children, ed 3, New York, 2014, Cambridge University Press, p. 713.
A solitary, congenital liver cyst (nonparasitic) can occur in childhood and has been identified in some cases on prenatal ultrasound. Abdominal distention and pain may be present, and a poorly defined right-upper-quadrant mass may be palpable. These benign lesions are best left undisturbed unless they compress adjacent structures or a complication occurs, such as hemorrhage into the cyst. Operative management is generally reserved for symptomatic patients and enlarging cysts.
Choledochal Cysts
Choledochal cysts are congenital dilatations of the common bile duct that can cause progressive biliary obstruction and biliary cirrhosis. Cylindrical (fusiform) and spherical (saccular) cysts of the extrahepatic ducts are the most common types (see Table 392.1 ). Choledochal cysts are classified according to the Todani method ( Fig. 392.1 ). Type 1 choledochal cysts, the most common variant, involve a saccular or fusiform dilation of the common bile duct. Type II cysts are congenital diverticula protruding from the common bile duct. Type III cysts or choledochoceles involve a herniation of the intraduodenal segment of the common bile duct into the duodenum. Type IVa cysts or Caroli disease involve multiple intrahepatic and extrahepatic cysts. Type IVb cysts involve only the extrahepatic duct. Solitary liver cysts (type V) are very rare.
The pathogenesis of choledochal cysts remains uncertain. Some reports suggest that junction of the common bile duct and the pancreatic duct before their entry into the sphincter of Oddi might allow reflux of pancreatic enzymes into the common bile duct, causing inflammation, localized weakness, and dilation of the duct. It has also been proposed that a distal congenital stenotic segment of the biliary tree leads to increased intraluminal pressure and proximal biliary dilation. Other possibilities are that choledochal cysts represent malformations of the common duct or that they occur as part of the spectrum of an infectious disease that includes neonatal hepatitis and biliary atresia.
Approximately 75% of cases appear during childhood. The infant typically presents with cholestatic jaundice; severe liver dysfunction including ascites and coagulopathy can rapidly evolve if biliary obstruction is not relieved. An abdominal mass is rarely palpable. In an older child, the classic triad of abdominal pain, jaundice, and mass occurs in <33% of patients. Features of acute cholangitis (fever, right-upper-quadrant tenderness, jaundice, and leukocytosis) may be present. The diagnosis is made by ultrasonography; choledochal cysts have been identified prenatally using this technique. Magnetic resonance cholangiography is useful in the preoperative assessment of choledochal cyst anatomy.
Choledochal cysts have the potential to develop into cholangiocarcinoma; therefore the treatment of choice is primary excision of the cyst and a Roux-en-Y choledochojejunostomy. The postoperative course can be complicated by recurrent cholangitis or stricture at the anastomotic site. Long-term follow-up is necessary to ensure that no malignancy develops.
Autosomal Recessive Polycystic Kidney Disease
Autosomal recessive polycystic kidney disease (ARPKD) manifests predominantly in childhood (see Chapter 541.2 ). Bilateral enlargement of the kidneys is caused by a generalized dilation of the collecting tubules. The disorder is invariably associated with congenital hepatic fibrosis and various degrees of biliary ductal ectasia, discussed in detail later.
The polycystic kidney and hepatic disease 1 (PKHD1) gene, mutated in ARPKD, encodes a protein that is called fibrocystin/polyductin, which is localized to cilia on the apical domain of renal collecting cells and cholangiocytes. The primary defect in ARPKD may be ciliary dysfunction related to the abnormality in this protein. Fibrocystin/polyductin appears to have a role in the regulation of cellular adhesion, repulsion, and proliferation and/or the regulation and maintenance of renal collecting tubules and bile ducts, but its exact role in normal and cystic epithelia remains unknown. Kidney and liver disease are independent and variable in severity; they are not explainable by the type of PKHD1 mutation. Phenotypic variability among affected siblings suggests the importance of modifier genes as well as possibly environmental influences.
In ARPKD, the cysts arise as ectatic expansions of the collecting tubules and bile ducts, which remain in continuity with their structures of origin. ARPKD normally presents in early life, often shortly after birth, and is generally more severe than autosomal dominant polycystic kidney disease (ADPKD). Fetal ultrasound may visualize large echogenic kidneys, also described as bright, with low or absent amniotic fluid (oligohydramnios). However, in many instances the features of ARPKD are not visualized on sonography until the 3rd trimester or after birth.
Patients with ARPKD can die in the perinatal period owing to renal failure or lung dysgenesis. The kidneys in these patients are usually markedly enlarged and dysfunctional. Respiratory failure can result from compression of the chest by grossly enlarged kidneys, from fluid retention, or from concomitant pulmonary hypoplasia. The clinical pathologic findings within a family tend to breed true, although there has been some variability in the severity of the disease and the time for presentation within the same family. In patients surviving infancy because of a milder renal phenotype, liver disease may be a prominent part of the disorder. The liver disease in ARPKD is related to congenital malformation of the liver with varying degrees of periportal fibrosis, bile ductular hyperplasia, ectasia, and dysgenesis. Initial symptoms are liver related in approximately 26% of patients. This can manifest clinically as variable cystic dilation of the intrahepatic biliary tree with congenital hepatic fibrosis. Congenital hepatic fibrosis and Caroli disease likely result from an abnormality in remodeling of the embryonic ductal plate of the liver. Ductal plate malformation refers to the persistence of excess embryonic bile duct structures in the portal tracts. ARPKD patients with recurrent cholangitis or complications of portal hypertension may require combined liver-kidney transplant.
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