The hepatobiliary system originates as a cluster of endodermal cells that forms a diverticulum from the duodenal region of the primitive embryonic gut. The diverticulum divides into 2 components between gestation weeks 18 and 22. (1) A solid cranial component (the pars hepatica) gives rise to the liver and intrahepatic portion of the biliary system, and (2) a hollow caudal component (the pars cystica) gives rise to the gallbladder (GB) and extrahepatic portion of the biliary system.

Cords of cells from the pars hepatica grow into the vascular mesenchyme and the adjoining septum transversum. The vasculature, lymphatics, and connective tissue of the liver develop from the vascular mesenchyme of this septum. Embryonic capillaries dilate to form the hepatic sinusoids. Cells in the walls of these capillaries differentiate into the reticuloendothelial cells of the liver. The hepatic parenchyma and lining cells of the intrahepatic bile ducts develop from endodermal cells of the pars hepatica.

During the eighth week of gestation, hepatic precursor cells in the hilar region form a sleeve-like layer of cells around portal veins (PVs), with subsequent extension into the periphery of the liver. This sleeve of tissue is termed the ductal plate. Intrahepatic bile ducts arise by way of remodeling and partial involution of these cylindrical ductal plates. The initial single-layer ductal plate soon becomes double-layered, thereby defining a slit-like primitive bile duct lumen between the 2 layers. There is subsequent extensive resorption of the ductal plate tissue leading to the formation of a network of fine bile ducts surrounding the PV. Bile duct formation by this process of ductal plate remodeling progresses from larger ducts to segmental and lobar branches and finally to small peripheral ductules.

The pars cystica gives rise to the GB, cystic duct, and extrahepatic bile ducts. In the early stages of development, endodermal cells fill the lumina of these structures. Canalization begins at approximately gestation week 7. The independently developing intrahepatic and extrahepatic components of the biliary system unite to establish continuity of the biliary drainage system by gestation month 3. Hepatic secretion of bile begins during gestation week 12. Secretion of bile into the duodenum occurs between weeks 13 and 16. Hematopoiesis occurs in the fetal liver and is still active at birth; this extramedullary hematopoietic activity ceases by approximately 6 weeks of age in normal infants.

Anomalies related to abnormal development of the ductal plates (i.e., ductal plate malformations) constitute a spectrum of hepatobiliary lesions, termed fibropolycystic liver disease. Congenital hepatic fibrosis and bile duct hamartomas are due to ductal plate malformations of the small interlobular bile ducts. Autosomal dominant polycystic disease results in ductal plate malformations of the medium-sized intrahepatic ducts. Ductal plate malformations of the large intrahepatic bile ducts occur in patients with Caroli disease. Some choledochal cysts (CCs) are apparently related to ductal plate malformations of the main bile duct. In some patients, manifestations of more than one of these pathological patterns coexist.¹

The liver is the largest solid organ in the body. At birth, the normal liver weighs approximately 175 g and accounts for nearly 5% of total body weight. Hepatic growth is disproportionately slower than that of the remainder of the body, such that the liver accounts for approximately 2% of body weight in normal adults. The equation L = 3.8 + 0.46A provides an estimate of the normal craniocaudal length of the liver normal children, where L is the span of the liver in centimeters at the midclavicular line and A is the age in years. The liver receives 25% to 30% of the cardiac output. Between 70% and 80% of the blood supply to the liver is via the portal venous system.

The main anatomic divisions of the liver are 2 main lobes (right and left) and 2 small lobes (caudate and quadrate). There are 2 lesser divisions of the right lobe (anterior and posterior segments) and 2 lesser divisions of the left lobe (medial and lateral segments). Accurate localization of space-occupying lesions to appropriate lobar and segmental divisions with imaging studies is essential for assessing potential resectability of hepatic lesions. The hepatic vessels serve as landmarks for defining the lobar and segmental anatomy of the liver on imaging studies. However, the conventional division into right and left lobes does not coincide exactly with the intrahepatic pattern of vascular and ductile branching.

The portal venous branches, hepatic artery branches, and biliary radicles generally run parallel to each other within the liver and are situated in the centers of the hepatic segments. The hepatic veins course between the hepatic segments and, therefore, are particularly useful in defining the segmental anatomy on imaging studies. There are 3 major hepatic venous branches: right, middle, and left. An imaginary plane drawn between the middle hepatic vein and the long axis of the GB defines the separation between the right and left hepatic lobes. A line between the left hepatic vein and the inferior vena cava (IVC) divides the medial and lateral segments of the left lobe. This line also passes through the intersegmental fissure, which contains the falciform ligament and the ligamentum teres hepatis. Division of the right lobe into anterior and posterior segments is by a line drawn between the right hepatic vein and the IVC. A line drawn between the middle hepatic vein and the IVC separates the anterior segment of the right hepatic lobe from the medial segment of the left lobe. The caudate lobe is located between the IVC and the ligamentum venosum. The fissure for the ligamentum venosum separates the caudate lobe from the quadrate lobe.

Supernumerary hepatic fissures that create accessory lobes are rare developmental variations that are generally of no clinical significance. Horizontal grooves along the anterior surface of the liver related to invaginations of the diaphragm and peritoneum are additional variations that are sometimes visible on cross-sectional imaging studies. These do not, however, represent true supernumerary fissures. Elongation of the right lobe of the liver is termed a Riedel lobe; this represents a normal variation that is occasionally mistaken for pathological hepatomegaly on physical examination and diagnostic imaging.

Myriad local and systemic diseases affect the liver. These include vascular, metabolic, toxic, obstructive, and neoplastic disorders. The most common clinical consequences of liver disease are jaundice and hepatic failure. In some instances, hepatomegaly or a palpable right upper quadrant mass detected in a patient with no overt symptoms provides the initial clinical indication of liver pathology. There is enormous functional reserve of the liver. Although obstructive jaundice can occur due to a small lesion, most other hepatic pathology must cause extensive parenchymal damage before symptoms occur.

Jaundice is the clinical term for yellow-green discoloration of the skin and sclera caused by hyperbilirubinemia. Bilirubin is the final degradation product of porphyrin metabolism. The breakdown of red blood cell hemoglobin accounts for approximately 85% of bilirubin production; additional sources include myoglobin, cytochromes, and catalase. The metabolic pathway for normal bilirubin clearance consists of (1) extraction from plasma by hepatocytes, (2) conjugation to glucuronic acid in hepatocytes, (3) excretion of conjugated bilirubin into biliary canaliculi, and (4) passage through the biliary system into the GI tract. The pathophysiology of jaundice is related to biliary duct obstruction, the overproduction of bilirubin, or any process that interferes with normal hepatic bilirubin metabolism.

The major classification of hyperbilirubinemia is based on the relative levels of conjugated and unconjugated serum bilirubin. In unconjugated hyperbilirubinemia, at least 85% of the total bilirubin is of the indirectly reacting type. If at least 30% of the total bilirubin is of the directly reacting type, there is conjugated hyperbilirubinemia. Mixed hyperbilirubinemia refers to directly reacting bilirubin levels between 15% and 30%.

Because elevation of indirectly reacting bilirubin usually indicates the presence of biliary obstruction, the terms cholestatic jaundice or obstructive jaundice are often used synonymously with conjugated hyperbilirubinemia. Likewise, unconjugated hyperbilirubinemia can be referred to as noncholestatic or nonobstructive jaundice. The type of jaundice is an important consideration in the differential diagnosis of liver disorders; however, there is variability in the expression of jaundice in different patients with the same disease and in the same patient during the course of a disease. Tables 41-1 and 41-2 provide general guidelines for the differential diagnosis of jaundice based on the type of hyperbilirubinemia and patient age. Jaundice due to hemolysis, sepsis, hepatic infection, bile plug syndrome, adrenal hemorrhage, or medications is often transient. Biliary atresia, neonatal hepatitis, choledochocele, and Alagille syndrome are associated with persistent jaundice.

The eventual result of severe liver dysfunction is the clinical syndrome of hepatic failure. Experimental evidence indicates that maintenance of clinically normal liver function requires as little as 10% to 20% of the hepatic parenchyma. Therefore, hepatic failure usually indicates the presence of severe diffuse liver disorders such as fulminant hepatitis and is only rarely associated with a focal lesion.

The clinical expression of hepatic failure relates to disturbance of any of the multiple normal hepatic metabolic functions. Metabolic hepatic encephalopathy refers to a constellation of personality alterations, confusion, and mental obtundation that occurs with severe hepatic dysfunction. Renal insufficiency frequently accompanies fulminant hepatic failure; this is termed hepatorenal syndrome. Pruritus is a common clinical complaint of patients with hepatic disease. Defective hepatic protein synthesis may lead to hypoalbuminemia, hypoglobulinemia, or hypoprothrombinemia.

Because of the extensive functional reserve of the liver, hepatomegaly is often the only clinical sign of liver disease. Generally, hepatomegaly is suggested on physical examination when the liver edge is palpable more than 3 cm below the right costal margin in infants or beyond 2 cm in older children. Table 41-3 lists important considerations in the differential diagnosis of hepatomegaly in infants and children.

There are 4 major types of liver injury: hepatocellular, autoimmune, cholestatic, and infiltrative. These categories are not mutually exclusive; more than 1 type of liver injury can occur in the same patient. Laboratory findings can help determine the predominant pattern of liver injury. Hepatocellular injury is characterized biochemically by elevation of serum transaminases. The most common causes of liver injury that lead to isolated or predominant elevation of serum transaminases include celiac disease, hepatitis B, hepatitis C, hemochromatosis, and nonalcoholic steatohepatitis; alcohol abuse is the most common cause in adults. The cholestatic and infiltrative types of liver injury are associated with elevations of serum alkaline phosphatase and normal or only mildly elevated serum transaminases. The cholestatic diseases result in markedly elevated bilirubin levels. Autoimmune liver diseases can produce a hepatocellular pattern if there is predominant involvement of the hepatocytes (e.g., autoimmune hepatitis) or a cholestatic pattern if the bile ducts are predominantly involved (e.g., primary biliary cirrhosis).

Congenital Lobar Agenesis and Hypoplasia

Agenesis or hypoplasia of a hepatic lobe is an uncommon developmental anomaly. Recognition of these anomalies is important to prevent misinterpretation of imaging studies and for preoperative planning. The right lobe is most commonly affected. The uninvolved lobe undergoes compensatory hypertrophy. Anomalies of GB morphology and position frequently accompany hepatic lobar agenesis or hypoplasia. The imaging diagnosis of lobar agenesis or hypoplasia is based on recognition of the abnormal hepatic contour, the orientation of hepatic landmarks (e.g., the GB and ligamentum teres hepatis), and the vascular anatomy (e.g., the presence or absence of the right or left hepatic vein).

Situs Abnormalities

A left upper quadrant position of the liver in a mirror-image orientation relative to the normal situation occurs with abdominal situs inversus. Hepatic malposition also is common in patients with heterotaxy syndrome. This usually occurs in the form of an abnormal symmetric configuration of the liver across the upper abdomen (i.e., a “transverse liver”); this appearance is present in approximately 80% of patients with asplenia and 50% with polysplenia (see Chapter 43). Visualization of this abnormal hepatic contour on chest and abdominal radiographs is an important initial imaging clue to the presence of visceral heterotaxy. Scintigraphy or cross-sectional imaging provides confirmation and characterization of suspected hepatic malpositions.

Diaphragmatic Herniation

Portions of the liver can protrude into the thorax through a congenital diaphragmatic hernia or eventration. The large congenital diaphragmatic hernias that present in the neonatal period almost always occur on the left side, so that herniation of hepatic tissue does not occur or is minimal. Large right-sided diaphragmatic hernias are uncommon; most or all of the liver can migrate into the thorax in these children. Smaller hernias or eventrations in which only a portion of the liver extends into the hemithorax may be mistaken for pulmonary pathology or a primary thoracic neoplasm on chest radiographs. Anterior herniation of the liver can occur through the foramen of Morgagni; this is nearly always unilateral. Supplemental evaluation with scintigraphy, sonography, CT, or MR readily demonstrated the variant anatomy in children with liver herniation.

Gallbladder Anomalies

The GB is absent in most patients with biliary atresia. Isolated congenital absence of the GB is a very rare anomaly that is usually associated with developmental lesions of other organ systems. Duplication anomalies of the GB are also rare; these can be partial or complete (Figure 41-1). Complete duplication includes the presence of 2 cystic ducts. Developmental septations can also occur in the GB. There are 5 positional anomalies of the GB: intrahepatic, suprahepatic, retrohepatic, left-sided, and floating. A congenitally floating or mobile GB is at some risk for torsion.

Biliary Atresia

Biliary atresia refers to absence of a variable portion of the biliary system. This is the most common congenital abnormality of the biliary system. The prevalence is approximately 1 in 15,000 newborns. This disorder is the most frequent cause of early childhood death due to hepatic dysfunction in industrialized nations. Biliary atresia is somewhat more common in girls than in boys (1.4:1). The cause of biliary atresia is unknown; proposed etiologies include injury to the vascular supply to bile ducts, abnormal bile acids, and viral infection. Genetic factors may be important in the pathogenesis in some patients. Some instances (approximately 35%) of biliary atresia appear to be of fetal or embryonic origin and, therefore, are true congenital lesions; others are acquired due to an insult in the perinatal or late fetal periods of development.^2,3

The pattern of bile duct obstruction in children with biliary atresia varies between patients. By definition, there is absence of some portion of the bile ducts between the ampulla of Vater and the second-order intrahepatic branches. There is considerable variability among patients in the pattern of involvement of atresia in the biliary system, and various classification schemes are utilized in this regard. The main clinical significance of these classifications is in guiding surgical therapy. The pathophysiological consequence of this disorder is the complete inability to excrete bile.

At least 10% of patients with biliary atresia have some or all of a complex of congenital anomalies that includes heterotaxy, polysplenia, azygos continuation of the IVC, bilateral bilobed lungs, preduodenal PV, and anomalous origin of the hepatic artery. The congenital heart diseases that are typically associated with polysplenia generally do not occur in this group of patients.

The typical clinical presentation of biliary atresia is prolonged neonatal jaundice, with persistence beyond the usual duration of physiological jaundice. Conjugated hyperbilirubinemia is present at birth in 75% to 80% of infants with biliary atresia and develops within the first month in the remainder. Hepatomegaly, acholic stools, and elevated serum transaminase and alkaline phosphatase values are additional common clinical features. The clinical findings in infants with biliary atresia are usually very similar to those of idiopathic neonatal hepatitis.

The ultrastructure of intrahepatic biliary canaliculi, as determined by transmission electron microscopy, has important prognostic significance in biliary atresia. The survival rate for patients with well-developed intrahepatic biliary canaliculi is greater than 90%, whereas those with poorly developed intrahepatic biliary canaliculi have a survival rate of approximately 33%.⁴ Disease severity and prognosis can also be assessed with sonographic criteria. Doppler findings indicative of a poor prognosis include a maximum portal flow velocity of lower than 16 cm/s, flattening of the normal triphasic hepatic vein flow curve, or a hepatic artery resistive index of 0.8 or more.⁵ The presence of 1 or more of these findings indicates a heightened risk for rapid deterioration and death; these patients require early intervention and listing for transplantation. If on serial examinations the resistive index increases to higher than 1.0, upgrading of the priority for transplantation may be indicated.⁶

In most infants with biliary atresia, there is no sonographically demonstrable GB or bile main bile duct (Figure 41-2). Others have a small GB that has an irregular contour and lacks a normal echogenic mucosal lining. There is usually absent or diminished postprandial GB contraction in patients with biliary atresia. A relatively specific sonographic finding in biliary atresia is the triangular cord sign. This refers to a triangular or band-like periportal echogenicity in a cone-shaped periportal fibrous mass at the bifurcation of the PV in the porta hepatis. This is most often identified cranial to the PV. In the differentiation between biliary atresia and infantile intrahepatic cholestasis, the triangular cord sign is reported to have a positive predictive value of more than 95%; however, the sensitivity is limited, as this finding is not identifiable in many children. An alternative technique is measurement of the thickness of the echogenic anterior wall of the right PV; a thickness of greater than 4 mm indicates biliary atresia with a sensitivity of 80% to 95%. Additional sonographic criteria of biliary atresia are lack of visualization of the common bile duct, enlargement of the hepatic artery, and a spherical or teardrop cyst in the porta hepatis (remnant of the extrahepatic duct). Proposed criteria for the diagnosis of biliary atresia based on measurements of the proximal right hepatic artery include a diameter of greater than 1.5 mm and a ratio of hepatic artery diameter to adjacent PV diameter greater than 0.45.^7–12

Hepatobiliary scintigraphy of patients with biliary atresia shows a lack of tracer excretion into the bowel (Figure 41-3). Excretion of radiopharmaceutical into the bowel effectively rules out the diagnosis of biliary atresia. Lack of excretion, however, occurs with various hepatic abnormalities in addition to biliary atresia; therefore, the specificity of this finding is limited. There is additional discussion of the scintigraphic evaluation of jaundiced infants in the following section on neonatal cholestasis.

MR cholangiography can be utilized to supplement standard imaging in patients with suspected biliary atresia. Typically, MR cholangiography in a patient with biliary atresia fails to demonstrate patent bile ducts. In some patients, there is periportal thickening, apparently related to fibrosis. The demonstration of an intact extrahepatic biliary tract effectively rules out the diagnosis of biliary atresia.¹³

Cholangiography shows 70% of biliary atresia patients to have totally obliterated extrahepatic bile ducts, 22% to have patency of the GB and distal common duct, and 8% to have obliterated extrahepatic ducts and patent proximal ducts (Figure 41-3). Contrast introduced via percutaneous transhepatic cholangiography, percutaneous cholecystography, or intraoperative cholangiography sometimes produces a coarse “stain” in the central aspect of the liver due to numerous small proliferated bile ducts.¹⁴

Preoperative cholangiography is usually not required for children who have classic clinical and imaging features of biliary atresia. However, in those jaundiced infants with a sonographically visible GB, percutaneous puncture of this structure is a safe and effective technique for contrast visualization of the biliary system. Percutaneous transhepatic cholangiography is another option, but has a lower success rate; Hashimoto reported successful visualization of the intrahepatic biliary system by the transhepatic technique in 47% of 19 infants between 30 and 90 days of age. If cholangiography demonstrates patent intrahepatic and extrahepatic bile ducts, biliary atresia is ruled out.¹⁵

There are reports on the use of endoscopic retrograde cholangiopancreatography (ERCP) for the evaluation of infants with suspected biliary atresia. Ohnuma et al described 4 ERCP patterns of biliary atresia: (1) visualization of the pancreatic duct alone or the pancreatic duct and a choledochal cyst with no other bile duct (35 of 46 patients); (2) visualization of a short and dilated blind ending common bile duct (1 of 46); (3) visualization of a thin common bile duct and narrow intrahepatic ducts (2 of 46); and (4) visualization of a thin common bile duct and small GB, without intrahepatic ducts (8 of 46). A common channel with the pancreatic biliary duct was observed in 11 of the 46 patients.¹⁶ Guelrud et al described 3 patterns: (1) no bile duct opacification (35% of patients); (2) opacification of the GB and common bile duct, without visualization of the main hepatic duct (35%); and (3) opacification of the GB, common bile duct, and a portion of the main hepatic duct, with bile lakes at the porta hepatis (30%). A normal biliary tree was present in all patients with neonatal hepatitis.¹⁷

The surgical management of infants with biliary atresia consists of the anastomosis of a roux-en-Y segment of jejunum to the hilum of the liver; this is the Kasai procedure or hepatoportoenterostomy. The surgical treatment should be undertaken as early in infancy as possible. Liver transplantation is the next-line therapy. According to the Biliary Atresia Registry of the Surgical Section of the American Academy of Pediatrics, predictors of a poor outcome following the Kasai procedure are white race, operative age of more than 60 days, evidence of cirrhosis by liver biopsy, completely obliterated extrahepatic ducts, absence of ducts at the level of transection of the liver hilus at operation, and subsequent development of varices or ascites.¹⁸ Doppler sonographic findings that predict poor survival without liver transplantation include diminished maximal portal venous velocities, elevated hepatic arterial resistive indices (≥0.8), and flattened hepatic venous waveforms.^5,19

Biliary scintigraphy serves to evaluate patency of a portoenterostomy in children with suspected obstruction following a Kasai procedure or transplantation. Visualization of the radiopharmaceutical within the bowel within 1 hour after IV administration suggests appropriate function. Patients with a portoenterostomy are at risk for ascending cholangitis. Cross-sectional imaging findings of cholangitis include irregular dilation of intrahepatic bile ducts and/or the formation of bile lakes.

Dynamic contrast-enhanced CT imaging of the liver can be useful in preparation for liver transplantation. Reported findings on CT imaging of children with end-stage biliary atresia, with or without a prior Kasai procedure, include hepatocellular nodules, intrahepatic biliary cysts, intrahepatic portosystemic shunts, intrahepatic communicating vessels between hepatic veins, and PV thrombosis. CT also assesses the PV diameter and detects hepatic artery anomalies.²⁰

Clinical Presentations: Neonatal Cholestasis

A broad spectrum of disorders causes cholestatic jaundice in the neonate or young infant. The differential diagnosis of neonatal jaundice includes a wide variety of parenchymal liver diseases that are caused by genetic disorders, metabolic abnormalities, or infectious diseases, as well as idiopathic conditions. Clinical and laboratory investigations provide a specific diagnosis for many of these conditions. When the clinical findings and laboratory studies for infectious, chemotoxic, or metabolic hepatocellular disorders fail to establish a specific etiology, the 2 most likely diagnoses are biliary atresia and idiopathic neonatal hepatitis (idiopathic hepatitis of infancy). Combined, these 2 disorders account for between 60% and 80% of cases of conjugated hyperbilirubinemia in neonates.

Both biliary atresia and neonatal hepatitis are idiopathic conditions. Some features of these disorders suggest that they are opposite extremes of the same or similar cholangiopathic processes. Viral infections may play a role in the pathophysiology. There are similarities between the 2 conditions on histological examinations; this overlap prevents a conclusive diagnosis on percutaneous liver biopsy in some cases. The diagnostic accuracy of liver biopsy for differentiating bile duct obstruction from parenchymal liver disease in infants with jaundice is approximately 85%.²¹

Despite the histological and clinical similarities of neonatal hepatitis and biliary atresia, the treatment strategies are substantially different. Early surgical intervention is essential for effective management of infants with biliary atresia, but surgery is not useful for those with idiopathic neonatal hepatitis. The lack of accurate clinical and laboratory criteria for the differentiation between these 2 disorders makes timely usage of appropriate imaging studies essential for proper patient management.

Sonography is the most appropriate initial imaging technique for the evaluation of infants with cholestatic jaundice. Sonography effectively detects many potential causes of obstructive jaundice that are included in the differential diagnosis, such as choledochal cyst, inspissated bile syndrome, ampullary stenosis, choledocholithiasis, biloma, and other obstructing masses. Although sonography does not allow an unequivocal diagnosis of neonatal hepatitis or biliary atresia, there are important findings on this examination nonetheless. The GB is sonographically normal in infants with neonatal hepatitis. The GB is small or absent in biliary atresia; the GB is not visible on sonographic studies in approximately 80% of neonates with biliary atresia. When the GB is identifiable, it has an abnormal rounded configuration in many cases of biliary atresia. Other potential sonographic findings in the jaundiced infant include hepatomegaly, splenomegaly, and alterations in hepatic parenchymal echogenicity; these findings, however, do not aid in the differentiation between biliary atresia and neonatal hepatitis. Careful examination of the spleen should be a part of the examination, because of the (uncommon) association of polysplenia with biliary atresia.

Hepatobiliary scintigraphy is the best available noninvasive diagnostic imaging technique for the assessment of hepatobiliary physiology. When properly performed biliary scintigraphy shows lack of excretion of radiolabeled bile into the bowel in a jaundiced infant, the most likely diagnosis is biliary atresia. The sensitivity of biliary scintigraphy for the diagnosis of biliary atresia approaches 100%. However, the specificity is much lower because several other conditions can have an identical scintigraphic appearance. Reported specificities for the scintigraphic diagnosis of biliary atresia range from 65% to 85%. Premedication with phenobarbital is important for optimizing hepatobiliary scintigraphy in the jaundiced infant. Phenobarbital is a potent inducer of hepatic microsomal enzymes and results in enhanced biliary excretion of conjugated bilirubin and other organic compounds, including the technetium-labeled iminodiacetic acid (IDA) derivatives that are used for biliary imaging.

Important factors in the interpretation of hepatobiliary scintigraphy in neonates with cholestasis include evaluation of the rapidity of clearance of the radiopharmaceutical from the blood pool, the degree and persistence of hepatic uptake, and the presence or absence of demonstrable passage of tracer into the bowel. The scintigraphic demonstration of excretion of tracer into the bowel effectively eliminates biliary atresia as a potential diagnosis. Excretion into the bowel is lacking in all patients with biliary atresia; however, this scintigraphic finding is not specific to this diagnosis, as there are various mimicking conditions. A lack of visible bowel activity during the initial phase of the study mandates the acquisition of additional images over a period of several hours. If GI activity is still absent on the delayed images, an additional injection of radiopharmaceutical can be given, with delayed imaging performed the following morning.

There are some instances of neonatal hepatitis in which polygonal cell function is compromised to the point that there is insufficient radiopharmaceutical extraction and excretion to allow visualization of bowel activity despite an anatomically patent biliary system. In these infants, evaluation of the dynamics of radiopharmaceutical extraction provides clues to the correct diagnosis. Infants who have marked polygonal cell dysfunction due to neonatal hepatitis characteristically have relatively slow accumulation of tracer within the liver parenchyma and slow clearance from the blood pool. In this situation, hepatic activity in the early phase after injection primarily represents hepatic blood pool rather than extracted radiopharmaceutical. The heart serves as the standard for blood pool activity in the quantitative and qualitative assessment of hepatic uptake. In infants with severe polygonal cell dysfunction, comparison of hepatic and cardiac activities with computer-generated time-activity curves shows slow clearance of activity from both areas, resulting in curves that have a similar shape and slope. In infants with preserved liver function, there is rapid increase in hepatic activity and rapid decrease in cardiac blood pool activity during the first several minutes of the study because of rapid extraction of radiopharmaceutical by the hepatic polygonal cells. Slow decrease in hepatic activity follows this initial phase, due to excretion into the biliary system and passage into the bowel.

In young infants with biliary atresia, preserved polygonal cell function usually allows rapid clearance of tracer from the blood pool and prompt hepatic uptake. Therefore, the time-activity curves of infants with biliary atresia initially show a rapid increase in hepatic activity similar to that seen in normal individuals. Subsequently, however, there is only a slow decrease in activity and the curve slope is similar to that of cardiac clearance; this pattern is due to the failure of excretion into the bowel (Figure 41-4).

Untreated biliary atresia leads to progressive liver damage early in infancy. After approximately 3 months, cirrhosis in an untreated infant may be associated with liver dysfunction of sufficient severity to compromise hepatic extraction of tracer. In this situation, an imaging pattern identical to that of severe neonatal hepatitis can occur, including nonvisualization of tracer in the bowel. The pattern of hepatic and cardiac clearance identified on time-activity curves in these infants may substantially overlap that of neonatal hepatitis. Therefore, scintigraphy of infants who are older than 3 months is only accurate for the differentiation between biliary atresia and neonatal hepatitis if there is excretion of tracer in the GI tract. If tracer accumulation in the bowel is lacking and hepatic extraction of tracer is poor, the scintigraphic findings are indeterminate.

Cholangiography is useful for evaluating selected infants with neonatal cholestasis. If a GB is present, percutaneous puncture of this structure provides a simple and safe pathway for biliary system contrast opacification. In patients with neonatal hepatitis, cholangiography shows patent intrahepatic and extrahepatic ducts, although the ducts may be small. With biliary atresia, various patterns of ductile anatomy may occur; however, at least a portion of the biliary system is absent. In those infants with a GB, there may be a hypoplastic common duct and absence of the major intrahepatic ducts. Therefore, cholecystocholangiography does not rule out the diagnosis of biliary atresia unless there is opacification of the common hepatic duct and intrahepatic biliary system (Figure 41-5).

After biliary atresia, the most common causes of obstructive jaundice in infants are choledochal cyst, bile plug syndrome, and spontaneous perforation of the common bile duct. In general, sonography differentiates between these lesions; supplemental information with other noninvasive techniques, such as scintigraphy, is helpful for select patients. Cholangiography is sometimes required, however, for a definitive diagnosis of some forms of biliary tract obstruction and is therapeutic for conditions such as bile plug syndrome.²²

Intrahepatic Biliary Hypoplasia

Intrahepatic biliary hypoplasia refers to absence or reduction in the number of interlobular bile ducts. The major clinical consequence is chronic cholestasis. By definition, the cause of intrahepatic biliary hypoplasia is unknown; similar histological findings occur in association with various other diseases of the liver, including genetic disorders such as α_r-antitrypsin deficiency and impaired cholic acid synthesis, chromosomal abnormalities such as Down syndrome, and (rarely) intrauterine infections due to viruses such as rubella and cytomegalovirus. The idiopathic type of intrahepatic biliary hypoplasia occurs in 2 forms: a syndromic form (Alagille syndrome or arteriohepatic dysplasia) and a nonsyndromic form.

Alagille syndrome is due to mutations in the JAG1 or NOTCH2 genes. JAG1 encodes a ligand in the notch intercellular signaling pathway that is crucial in fetal development. Notch signaling is involved in the regulation of fetal intrahepatic biliary development. Most affected patients have neonatal jaundice or chronic cholestasis. Other features include abnormal facial development (i.e., prominent forehead, small pointed chin, hypertelorism, deep-set eyes, and poorly developed nasal bridge), pulmonary artery hypoplasia or stenosis, anterior vertebral defects (e.g., butterfly vertebrae), and growth retardation. Inner ear abnormalities (semicircular canal dysplasia), chronic otitis media, and deafness can occur. The liver involvement in Alagille syndrome causes a propensity for deficiencies of fat-soluble vitamins. Vitamin D deficiency can lead to rickets or osteomalacia.^23–25

Infants with intrahepatic biliary hypoplasia usually develop jaundice during the first 3 months of life. The syndromic variety may present somewhat later in infancy. Hepatomegaly is invariably present, and splenomegaly occurs in approximately half of patients with this disorder. Individuals with the syndromic form of intrahepatic biliary atresia may live into early adulthood with appropriate therapy. The prognosis with the nonsyndromic variety is less favorable; most of these patients succumb to liver failure during the first few years of life.

The clinical presentation and imaging characteristics of intrahepatic biliary hypoplasia are similar to those of biliary atresia. An accurate diagnosis is essential, however, since early surgical intervention is beneficial in biliary atresia but is not indicated in biliary hypoplasia. Clinical and radiographic recognition of the extrahepatic characteristics that are associated with the syndromic form of biliary hypoplasia is important. However, the presence and severity of these associated abnormalities vary considerably between patients.

There are no specific features of intrahepatic biliary hypoplasia on standard radiographs. Hepatomegaly and splenomegaly may be present in older children. In patients with the syndromic form, potential radiographic findings include butterfly thoracic vertebrae, short distal phalanges, short ulnae, and retarded bone age. Chest radiographs may show manifestations of pulmonary artery stenosis or pulmonic atresia.

The GB may or may not be sonographically visible in children with biliary hypoplasia. The bile ducts are normal or small. In older children, hepatic echogenicity is often prominent due to cirrhosis; regenerating nodules are sometimes present. The liver is usually enlarged, particularly the left lobe. Associated splenomegaly is sometimes present.

The findings of intrahepatic biliary hypoplasia on hepatobiliary scintigraphy vary between patients. Some of these infants have mildly delayed hepatic uptake and a lack of tracer visualization within the biliary tree and bowel; this appearance is indistinguishable from that of biliary atresia. In others, there is excretion into the gut (typically with a prolonged parenchymal transit time), producing a scintigraphic pattern indistinguishable from that of idiopathic neonatal hepatitis.

Percutaneous or operative cholangiography of patients with intrahepatic biliary hypoplasia demonstrates patency of the extrahepatic biliary tree. The intrahepatic bile ducts are sparse. Documentation of patency of the entire extrahepatic biliary system with cholangiography or biliary scintigraphy, while not specific for biliary hypoplasia, absolutely excludes the diagnosis of biliary atresia. Liver biopsy typically allows a definitive diagnosis of intrahepatic biliary hypoplasia. Percutaneous biopsy usually provides a diagnostic specimen, although an open-wedge biopsy is sometimes needed to obtain sufficient tissue for a confident histological diagnosis.²⁶

Byler Disease

Byler disease (progressive intrahepatic cholestasis) is the second most common form of familial intrahepatic cholestasis, after Alagille syndrome. Unlike Alagille syndrome, Byler disease is not associated with anomalies of other organ systems. The pathological features of Byler disease include a paucity of bile ducts, giant cell transformation, periportal fibrosis, periportal cysts, and cirrhosis. The hepatic cysts that occur in these patients may represent retention cysts of the periductal glands. The clinical presentation of Byler disease is usually in infancy, with hepatomegaly, pruritus, and jaundice. Diagnostic imaging studies show enlargement of the liver and multiple intrahepatic cysts that do not communicate with the bile ducts. In some patients, CT shows enhancing vessels within the cystic lesions, that is, the “central dot sign.”

Choledochal Cyst

CC is a congenital biliary lesion in which there is fusiform or diverticular dilation of the common bile duct and/or common hepatic duct. In contradistinction to other cystic malformations of the biliary tract, CC is not accompanied by substantial hepatic fibrosis and is only rarely associated with cystic renal disease. There are rare instances of CC occurring in combination with extrahepatic biliary atresia. CC is more common in girls and in individuals of Asian descent.

There are various classification schemes for CC. The system proposed by Alonso-Lej recognizes 4 types and various subtypes. Type I is fusiform dilation of the common bile duct, type II is a diverticulum of the common bile duct, type III is cystic dilatation of the terminal portion of the common bile duct (choledochocele), and type IV is Caroli disease.²⁷ Todani et al developed an additional commonly utilized classification system that defines 5 major types and several subtypes of CC. Type I refers to dilation of the common bile duct; type II is a diverticulum of the common duct; type III is a choledochocele; type IV refers to multiple intrahepatic or extrahepatic communicating cysts; and type V is Caroli disease.²⁸

The Alonso-Lej type I CC is the most common. This type is more frequent in girls than in boys. The characteristic feature that is present in most, but not all, patients with a type I lesion is an anomalous pancreaticobiliary junction, with an elongated common pancreaticobiliary channel. The anomalous pancreaticobiliary junction likely is the key feature in the pathogenesis of the choledochocyst in these individuals. (1) The lack of a sphincter at the anomalous pancreaticobiliary junction allows reflux of pancreatic fluid into the common bile duct, inducing chronic cholangitis and ductal and periductal fibrosis; (2) scarring eventually leads to partial distal bile duct obstruction; and (3) the weakened duct wall bulges to form a CC.

Although the etiology of type II CC is unknown, the pancreaticobiliary junction is normal. Potential pathogenic mechanisms for the formation of a type III CC (choledochocele) include obstruction of the papilla due to inflammatory changes, diverticulum formation between contracting ampullary and common duct components of the sphincter of Oddi, and a congenital duodenal diverticulum that arises near the ampulla of Vater and subsequently communicates with the intramural portion of the common bile duct. There is no gender predilection with type III CC.

The age at clinical presentation defines 2 groups of CC patients. Approximately 30% of patients with CC present during infancy. These infants often have clinical findings that are clinically indistinguishable from those of biliary atresia, for example, cholestatic jaundice. Approximately 5% of cases of infantile jaundice are due to CC. The late-onset group (mean age of 9 years) presents with various combinations of the classic triad of pain, abdominal mass, and jaundice. Fever due to cholangitis is an additional common finding. Biliary obstruction in infants with CC is sometimes due to the presence of a bile plug (i.e., tumefactive sludge); this can be associated with spontaneous perforation of the common duct. In untreated patients, intermittent biliary stasis can lead to recurrent bouts of ascending cholangitis, progressive biliary cirrhosis, portal hypertension, varices, and hepatic failure. There is a case report of a young child with life-threatening hematobilia due to pseudoaneurysm formation adjacent to a CC. There is a 20-fold increase in the prevalence of carcinoma of the biliary tree in individuals with CC compared to the normal population. The prevalence in these patients is approximately 1% during the first 2 decades of life and 14% during adulthood.^29,30

Abdominal radiographs of children with CC are often normal. In some patients, there is fullness or a soft tissue mass in the right upper quadrant. Upper GI barium studies may show extrinsic compression of the first and second portions of the duodenum. Rarely, calcifications are visible in the cyst wall. Intraluminal calculi may develop in a CC in older children and adults. A type III CC appears as a filling defect in the medial aspect of the contrast-opacified C-sweep of the duodenum on an upper GI study or CT (Figure 41-6).

Sonography is generally the initial imaging modality for the evaluation of children with obstructive jaundice or a suspected hepatobiliary mass. A CC is readily demonstrable with sonography. A type I cyst is imaged as replacement of the main bile duct with a fusiform cystic lesion that extends into the porta hepatis (Figure 41-7). There is often a branching pattern at the upper margin of the lesion due to associated dilation of central intrahepatic ducts. Echogenic biliary tract calculi are sometimes present.

Sonographic examination shows a type II CC as a round, anechoic, right upper quadrant mass. Communication with the dilated common bile duct may or may not be demonstrable with sonography. The intrahepatic bile ducts are often somewhat dilated. Choledochocele has a sonographic appearance similar to that of type II CC; the relationship of the cyst to the duodenum may be difficult to demonstrate sonographically. Gas in the duodenal lumen sometimes obscures the cyst.³¹

Although sonography is quite sensitive for the detection of a CC, the specificity is limited by the mimicking appearances of various other right upper quadrant cystic lesions. These include duodenal duplication cyst, pancreatic pseudocyst, mesenteric cyst, and hydrops of the GB. In those instances of CC in which there is intrahepatic bile duct dilation, appreciation of the more prominent nature of dilation in the extrahepatic ducts is important to avoid a misdiagnosis of Caroli disease.

CT readily demonstrates the location, morphology, and cystic character of CCs. A type I CC appears as a fusiform cystic structure that extends into the porta hepatis, with an abrupt change in caliber at the junction with the normal bile ducts. If the lesion involves the distal aspect of the common bile duct, the inferior aspect of the cyst is surrounded by the head of the pancreas (Figure 41-8). A type II lesion appears as a discrete round cyst in the porta hepatis region (Figure 41-9). In some patients, there is visualization of an adjacent normal or slightly dilated common bile duct; communication with the duct is sometimes discernable. The cyst wall may enhance with IV contrast. The CT appearance of a choledochocele consists of a cystic mass that is contiguous with the distal common bile duct and prolapses into the contrast-opacified duodenum.

Radionuclide biliary imaging in the diagnostic evaluation of CCs is particularly helpful for the unequivocal demonstration of communication of the cyst with the biliary system. The hepatocyte phase of biliary scintigraphy in these patients is normal or demonstrates extrinsic mass effect. The visualized proximal bile ducts on subsequent images may or may not be dilated. If the CC is large, it produces a photopenic area on the initial (hepatocyte phase) images. Unless there is proximal obstruction, subsequent images usually show appearance of tracer in the CC commensurate with tracer filling of the normal ducts. Because some degree of cholestasis is common in these patients, delayed images over a period of several hours may be required to demonstrate tracer accumulation in the cyst.

Although usually not required prior to surgery, cholangiography provides a definitive diagnosis and classification of CCs. With a type I CC, cholangiography shows fusiform or saccular dilatation of a portion or all of the main bile duct (Figure 41-10). The anomalous insertion of the common bile duct into the main pancreatic duct is often visible. Typically, there is an elongated common pancreaticobiliary channel, resulting in a T-shaped configuration (Figure 41-11). There is usually some degree of dilation of the pancreatic duct and the anomalous common pancreaticobiliary duct. The GB and intrahepatic bile ducts may also be dilated. Cholangiography shows types II and III CCs to have normal anatomic relationships at the pancreaticobiliary junction. The type II cyst consists of 1 or more diverticula of the extrahepatic bile ducts. The type III cyst is a focal dilation of the intraduodenal portion of the common bile duct.³²

The features of CC on MR are similar to those on other cross-sectional imaging studies. The signal intensity of the contents is identical or similar to that of fluid in the remainder of the biliary system (i.e., low signal on T1-weighted images and high signal on T2-weighted images). MR cholangiopancreatography (MRCP) shows similar findings as contrast cholangiography (Figure 41-12). In some patients, particularly older children, MRCP allows documentation of the anomalous ductal anatomy with a type I CC.³³

Caroli Disease

Caroli disease is a developmental disorder characterized by nonobstructive saccular dilatations of the first- and second-order branches of the intrahepatic bile ducts. Other terms for this condition include congenital biliary tract ectasia and congenital cystic dilatation of the biliary tract. Caroli disease is an autosomal recessive disorder. The saccular dilation of the bile ducts in patients with Caroli disease predisposes these patients to recurrent cholangitis, biliary lithiasis, liver abscess, and sepsis. In contradistinction to congenital hepatic fibrosis, portal hypertension does not occur in the pure form of Caroli disease. There is an elevated risk for development of cholangiocarcinoma within the abnormal biliary tract in patients with Caroli disease. As with congenital hepatic fibrosis, Caroli disease is frequently associated with cystic renal abnormalities, such as renal tubular ectasia.

Caroli disease and congenital hepatic fibrosis apparently represent opposite poles of a single cholangiopathic lesion. Based on the clinical, radiologic, and histologic characteristics, individual cases can be classified as congenital hepatic fibrosis, Caroli disease, or intermediate forms. Arrested remodeling of the ductal plates of large intrahepatic ducts apparently causes pure Caroli disease (“Caroli disease proper”). Intermediate forms of this disorder, sometimes termed “Caroli syndrome,” may be due to arrested remodeling both in the early period of bile duct embryogenesis and later during the development of more peripheral biliary ramifications.¹

The clinical features of the pure form of Caroli disease include recurrent bouts of cholangitis and hepatic abscesses related to bile stasis and gallstone formation in the ectatic bile ducts. Patients with an acute episode may have fever, pruritus, jaundice, liver tenderness, and modest elevations in serum bilirubin, transaminases, and alkaline phosphatase levels. Although the clinical onset can be at any age, the initial diagnosis of Caroli disease is usually during childhood or adolescence.

Congenital biliary ectasia associated with hepatic fibrosis is much more common than the pure form of Caroli disease. Portal hypertension is an important component of this form of congenital biliary tract ectasia. These children most commonly present in late childhood with hepatosplenomegaly. Upper GI bleeding is a common overt clinical manifestation of this disorder and is occasionally the presenting feature. Portal hypertension and hypersplenism due to the congenital hepatic fibrosis can lead to thrombocytopenia. Laboratory studies of liver function are frequently normal or only minimally abnormal. Potential complications of congenital biliary ectasia include cholangitis, biliary tract stones, and liver abscess.

In keeping with the pathologic spectrum of Caroli disease and congenital hepatic fibrosis, the findings on imaging studies are variable as well. With classic Caroli disease, there are multiple saccular lesions of the intrahepatic bile ducts. When hepatic fibrosis occurs in the absence of macroscopic biliary duct ectasia, imaging studies typically demonstrate nonspecific hepatosplenomegaly and heterogeneity of the liver parenchyma. The identification of the renal cystic abnormalities that frequently accompany this condition provides an important clue to the correct diagnosis.

In the presence of macroscopic biliary tract ectasia in children with Caroli disease or hepatic fibrosis, sonography demonstrates multiple anechoic cysts associated with the intrahepatic bile ducts (Figure 41-13). The visualization of communication between the cystic structures and the bile ducts aids in the differentiation from multicystic liver disease. The ectatic ducts frequently have irregular internal margins. Shadowing due to calculi is sometimes present.

Sludge or infection-related debris appears as echogenic material that lacks acoustic shadowing. The extrahepatic bile ducts and the GB are frequently enlarged, although the intrahepatic abnormalities are proportionately greater than the mild extrahepatic dilation. Additional sonographic findings that can be present in Caroli disease include intraluminal bulbar protrusions of the ductal wall, bridge formation across dilated ducts, and partial or complete surrounding of portal radicles by dilated bile ducts.^34,35

The sonographic examination of children with suspected Caroli disease should include a careful examination of the kidneys. The spectrum of renal findings in these patients ranges from nearly normal to severe polycystic disease. There is often renal parenchymal hyperechogenicity that can predominantly involve the medulla or extend throughout the kidney.

CT imaging shows the ectatic bile ducts of Caroli disease as multiple low-attenuation, branching tubular structures that communicate with focal cystic areas (Figure 41-14). Biliary calculi are common. An abscess is suggested if a cystic area has higher attenuation values than the remainder of the biliary tract. As with sonography, extrahepatic bile duct dilation, GB enlargement, splenomegaly, and renal abnormalities are ancillary findings of Caroli disease on CT.

An occasional CT feature of Caroli disease is a small enhancing focus surrounded by fluid (“the central dot sign”). The intensely enhancing focus represents a small PV branch. The ectatic bile duct wraps around the vessel. This pattern is in keeping with the ductal plate malformation pathogenesis. Occasionally, a thin membrane of fibrovascular tissue extends from the “central dot” to the peripheral margin of the cyst.³⁶

The intrahepatic cystic lesions of Caroli disease are hyperintense on T2-weighted MR images. The central dot sign is sometimes visible on contrast-enhanced images, as with CT. The MR signal intensities of calculi are variable. Cholangitis can lead to intraluminal debris, ductal wall thickening, and prominent periductal enhancement. MR cholangiography is useful for the noninvasive assessment of extrahepatic ductal anatomy.¹

The sulfur colloid scintigraphic findings of congenital hepatic fibrosis and Caroli disease range from normal to inhomogeneous uptake to multiple focal defects, depending on the sizes of the ectatic segments of the biliary system. Hepatomegaly or splenomegaly may or may not be present; these findings are most frequent when hepatic fibrosis is the dominant feature.

The findings with hepatobiliary scintigraphy are relatively specific in most cases of Caroli disease. The important feature during the hepatocyte phase of the examination is the presence of focal defects that correspond to the ectatic segments of the biliary system. Sequential images demonstrate gradual accumulation of radiopharmaceutical in these areas (Figure 41-15). Delayed images show relatively intense activity in the ectatic biliary system superimposed on a background of decreasing hepatic parenchymal activity. Because some degree of cholestasis is frequently present in patients with Caroli disease, there can be delayed passage of tracer into the bowel and slow clearance of activity from the ectatic bile ducts.

Most often, noninvasive imaging studies, in concert with appropriate clinical investigations, provide an accurate diagnosis of Caroli disease. Cholangiography is useful for indeterminate cases; contrast opacification of the biliary system in these patients is achieved with percutaneous transhepatic, endoscopic retrograde, or operative cholangiographic techniques. The characteristic cholangiographic appearance consists of dilated intrahepatic bile ducts that communicate with multiple biliary cysts. The dilated portions of the hepatic ducts may be saccular or fusiform. Filling defects due to tumefactive sludge and calculi are usually present. The extrahepatic bile ducts are often (but not invariably) somewhat dilated.

Congenital Hepatic Fibrosis

Congenital hepatic fibrosis is a developmental disorder of the biliary tract that is related to Caroli disease. The characteristic pathologic features are bands of fibrous tissue that contain dysplastic cystic structures lined with columnar biliary epithelium. Congenital hepatic fibrosis usually leads to portal hypertension, but hepatocellular function is almost always preserved. Congenital hepatic fibrosis only rarely occurs as an isolated abnormality; the most frequently associated condition is autosomal recessive polycystic kidney disease. Other entities that occasionally are associated with congenital hepatic fibrosis include autosomal dominant polycystic kidney disease, Meckel syndrome, renal dysplasia, choledochal cyst, Ivemark familial dysplasia, nephronophthisis, and medullary sponge kidney. Congenital hepatic fibrosis has an autosomal recessive pattern of inheritance in most patients.

The most common early manifestations of congenital hepatic fibrosis are related to portal hypertension: splenomegaly, varices, and GI hemorrhage. Most patients with this disorder present in adolescence or early adulthood, although the potential age range of clinical onset is from early childhood to the sixth decade of life. Because hepatocellular function is relatively preserved, liver function tests are normal or only mildly altered. The severity of liver fibrosis is usually progressive; evolution to true cirrhosis occurs in some patients.³⁷

Sonographic examination of children with congenital hepatic fibrosis shows hepatomegaly. The size of the spleen helps determine if there is substantial portal hypertension. Hepatic parenchymal echogenicity is prominent, either with a homogeneous or heterogeneous pattern. Areas of fibrosis tend to be hyperechoic. Cystic areas are sometimes present in the liver. The GB may be enlarged, and mild intrahepatic bile duct dilation is present in some patients. Additional congenital abnormalities of the biliary tree occur in some patients. The kidneys should be carefully examined for associated cysts or other lesions (Figure 41-16).

The CT findings of congenital hepatic fibrosis are nonspecific. Hepatomegaly is a consistent finding. The parenchyma usually has a heterogeneous appearance, with intermixed areas of increased and decreased attenuation. Most often, the left lateral segment of the liver is hypertrophied, the right lobe is atrophic, and the left medial segment is normal or hypertrophied. In some patients, there is enlargement of the hepatic artery, usually occurring in association with large regenerative nodules. On MR, there is abnormally diminished signal intensity of the liver parenchyma on both T1- and T2-weighted images. Periportal fibrosis results in low signal intensity bands within the hepatic parenchyma.¹

Polycystic Disease

Polycystic disease of the liver occurs in association with polycystic kidney disease. This condition occurs in autosomal recessive and autosomal dominant forms. Hepatic involvement is usually more severe with the recessive type. The hepatic findings of autosomal recessive polycystic disease consist of innumerable parenchymal liver cysts, periportal fibrosis, and dilation of bile ductules. Although the renal symptoms usually dominate in these patients, progressive intrahepatic fibrosis can result in symptomatic portal hypertension. Hepatomegaly is nearly always present, sometimes most prominently affecting the left lobe. Some children with autosomal recessive polycystic kidney disease have associated congenital hepatic fibrosis without cystic liver involvement.

In autosomal dominant polycystic liver disease, the distribution of hepatic cysts may be diffuse or localized. The cysts can be intrahepatic or peribiliary (i.e., multiple small cysts within the hepatic hilum or in the connective tissue adjacent to large portal triads). The cysts vary in size, ranging from a few millimeters to several centimeters in diameter. As with the recessive type, the cysts do not communicate with the biliary system. The renal abnormalities usually dominate the clinical picture; clinical manifestations of liver involvement are often lacking. Hepatomegaly is demonstrable in some of these patients. Portal hypertension is rare in patients with autosomal dominant polycystic liver disease. There are occasional instances in which 1 or more large cysts cause symptomatic obstruction of a portion of the biliary system.

Sonography is usually the only imaging modality that is required for evaluation of children with suspected polycystic liver disease. Sonography typically shows multiple round noncommunicating hepatic cysts of varying diameters. The diagnosis is usually confirmed by the sonographic demonstration of the characteristic renal abnormalities, that is, enlarged, hyperechoic kidneys in the autosomal recessive type and multiple variable-sized renal cysts (sometimes with calcifications) in the autosomal dominant type.

Other cross-sectional imaging studies, such as CT and MR, also show variable patterns of cystic disease of the liver and kidneys in these patients, as well as hepatomegaly and/or nephromegaly. On MR, signal intensities vary between cysts, apparently due to the presence of blood products. Sulfur colloid hepatic scintigraphy shows cysts of sufficient size as photopenic lesions. Hepatobiliary scintigraphy demonstrates the cysts as photopenic areas during the hepatocyte phase of the examination, with no subsequent accumulation of tracer on delayed images; this technique serves to document a lack of communication between the cysts and the bile ducts. Unless a cyst causes biliary obstruction, the bile ducts are usually normal in caliber in patients with polycystic liver disease, and there is normal excretion of tracer into the GI tract. Biliary scintigraphy in autosomal recessive polycystic kidney disease frequently shows enlargement of the left lobe of the liver and delay in peak hepatocyte uptake. Other potential findings include delayed excretion into the bile ducts or bowel, and bile duct dilation.³⁸

Biliary Hamartomas

Biliary hamartomas (von Meyenburg complex) are ductal plate malformations that are composed of dilated duct-like structures lined by biliary epithelium and containing fibrous stroma. The ductile remnants do not communicate with the biliary tract. Biliary hamartomas are usually asymptomatic. Most often, these occur as multiple small lesions scattered throughout the liver. Biliary hamartomas tend to be relatively uniform in size. The hamartomas produce low-attenuation on contrast-enhanced CT. They are hypointense on T1-weighted MR images and hyperintense on T2-weighted images. Hamartomas do not substantially enhance with contrast, although a peripheral enhancing rim is visible in some instances.¹

Congenital Solitary Hepatic Cyst

Congenital solitary hepatic cyst is an uncommon lesion in the pediatric age group. These cysts are usually small and asymptomatic; most are discovered as incidental findings on imaging studies for an unrelated indication. Symptoms are present in occasional patients, due to mass effect that causes biliary obstruction, stretching of the liver capsule, or bowel obstruction. Cyst perforation and secondary infection are rare complications. There are rare instances in which a congenital solitary hepatic cyst is large enough to produce a palpable mass. In addition to congenital solitary hepatic cyst, the differential diagnosis of an isolated hepatic cyst includes echinococcal cyst, amebic cyst, and cystic neoplasm.

The origin of a congenital solitary hepatic cyst likely is from an aberrant bile duct. The lesion is typically round or oval, and surrounded by a well-formed capsule. The cyst is multilocular in approximately 10% of affected patients. The lesion may be totally intrahepatic, partially intrahepatic, or pedunculated. There is a predilection for occurrence of congenital solitary hepatic cyst in the inferior aspect of the right lobe. Congenital solitary hepatic cyst nearly always occurs as an isolated lesion, and is not associated with renal or pancreatic cysts. There is an increased prevalence of congential hepatic cysts in patients with von Hippel-Lindau disease and Peutz-Jeghers syndrome.

Cross-sectional imaging studies show congenital solitary cyst as a well-demarcated cystic mass (Figure 41-17). The walls are thin and well defined. The contents are usually homogeneous, with no hemorrhage or debris. On CT, the contents have attenuation values in the 0 to 10 HU range. The cystic nature is indicated on sonography by an anechoic character, with distal acoustic enhancement. There is no communication with the biliary system, which can be confirmed when clinically relevant with biliary scintigraphy. There are rare instances in which the cyst is extrahepatic and pedunculated; the intraperitoneal component in these infants may be quite large. This lesion is included in the differential diagnosis of a large cystic abdominal mass in an infant (e.g., giant ovarian cyst, choledochocyst, duplication cyst, and mesenteric cyst).³⁹

Liver Parenchyma

Hepatitis is a nonspecific term that encompasses any form of diffuse inflammation of the liver, usually in association with hepatocyte degeneration or necrosis. Hepatitis can be infectious, toxic, traumatic, metabolic, or idiopathic. When cholestasis occurs in these various forms of hepatitis, it is a manifestation of biliary system obstruction, severe hepatocytic dysfunction, or both. The healing process of hepatitis consists of hepatocyte regeneration and collagen formation. A return to normal hepatic function without significant long-term sequelae is the usual outcome in pediatric patients of infectious hepatitis. However, chronic liver abnormalities sometimes occur, either from manifestations of the healing process or due to an ongoing hepatocyte insult. Excessive production of fibrous tissue in patients with hepatitis can lead to cirrhosis.

Chronic hepatitis refers to hepatic inflammation that lasts beyond 6 months. Causes of chronic hepatitis include a persistent viral infection, drugs, or toxins; in some patients, the etiology is unknown. There are 2 clinicopathological subgroups of chronic hepatitis: chronic persistent hepatitis and chronic active hepatitis. Patients with chronic persistent hepatitis have mild symptoms; full recovery of liver function usually occurs within several months to 2 years. Chronic active hepatitis most commonly occurs as an idiopathic autoimmune disorder. Chronic active hepatitis due to hepatitis B virus infection is a progressive disease that can lead to cirrhosis and liver failure.

Idiopathic Neonatal Hepatitis

Idiopathic neonatal hepatitis is the most common symptomatic primary liver disorder in early infancy, accounting for 35% to 45% of cases of cholestasis in this age group. Idiopathic neonatal hepatitis is more common in boys, in contradistinction to the female predilection with biliary atresia. Jaundice is clinically evident during the first week of life in approximately 80% of infants with neonatal hepatitis. Hepatomegaly is also common. Diagnostic imaging studies are important in the differentiation from biliary atresia.

On sonographic evaluation, there is a visible GB in at least 90% of patients with neonatal hepatitis. With severe hepatocellular disease, there is a collapsed GB due to poor bile excretion. In most infants with neonatal hepatitis, there is sufficient hepatic function for excretion of radiopharmaceutical into the gut. Cholangiographic studies demonstrate a normal patent biliary system in children with neonatal hepatitis. There is additional discussion of the imaging principles of neonatal hepatitis in the Neonatal Cholestasis section earlier in this chapter.

Viral Hepatitis

Cytomegalovirus and hepatitis B virus are the most common agents to cause acute viral hepatitis in the newborn. Cytomegalovirus hepatitis tends to produce chronic inflammation and fibrosis; clinically evident cirrhosis often occurs in these patients. Consequences of perinatal hepatitis B virus infection include development of a persistent carrier state and (rarely) fatal fulminant necrotic hepatitis. Perinatal herpesvirus, Coxsackie B virus, and echovirus infections are rare potential causes of fatal fulminant hepatic necrosis. Congenital rubella infection is sometimes associated with a perinatal hepatitis that is clinically indistinguishable from idiopathic neonatal hepatitis.

Viral agents that cause hepatitis in children beyond the neonatal age include hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, herpes simplex virus, Epstein-Barr virus, mumps, varicella, influenza, adenovirus, and coxsackievirus. Most of these agents produce a self- limited acute hepatitis. Potential short- and long-term sequelae of viral hepatitis (particularly hepatitis B virus infections) include a chronic carrier state, chronic persistent hepatitis, chronic active hepatitis, fulminant hepatitis, cirrhosis, and hepatocellular carcinoma. Virus-related hepatitis is a major health problem worldwide. Between 1% and 3% of individuals in the developed world are chronically infected with hepatitis C virus; infection rates in other countries are up to 35%.⁴⁰

Sonography of children with acute viral hepatitis is sometimes normal, or shows only mild nonspecific hepatomegaly. GB wall thickening can occur (Figure 41-18). An additional common sonographic finding in these patients is the centrilobular pattern: the walls of the portal venules are more clearly identified than normal, an increased number of portal venule walls are visualized, and the echogenicity of the walls is prominent. With severe disease, there is generalized diminution of parenchymal echogenicity. The fatty-fibrotic pattern is often identified in patients with chronic hepatitis, cirrhosis, and fatty infiltration: the echogenicity of the hepatic parenchyma is prominent, the walls of portal venules are poorly defined, and there may be accentuated attenuation of the beam.

In patients with acute uncomplicated hepatitis, CT often shows hepatomegaly and subtly diminished attenuation of the parenchyma. Regional lymphadenopathy may be present. In some patients, the GB wall is thickened and there is periportal hepatic hypoattenuation due to edema.

Sulfur colloid scintigraphy of patients with acute viral hepatitis is usually normal, aside from mild to moderate hepatomegaly. Additional potential findings include splenomegaly, mild redistribution of tracer to the spleen and bone marrow, and minimal parenchymal inhomogeneity. In those patients with fulminant hepatitis, the scintigraphic demonstration of marked colloid redistribution to the spleen and bone marrow is a sign of a grave prognosis; hepatomegaly and less severe colloid redistribution are more common with nonfatal cases.

Imaging of patients with chronic persistent hepatitis is either normal or demonstrates minimal hepatomegaly. A variable degree of hepatosplenomegaly may also be present in cases of chronic active hepatitis. Sulfur colloid scintigraphy of chronic active hepatitis often demonstrates redistribution of tracer to the spleen, bone marrow, and lungs (i.e., colloid shift). Progression of disease to cirrhosis and portal hypertension is indicated scintigraphically by heterogeneous hepatic uptake. Focal defects are sometimes present, due to regenerating nodules or localized areas of inflammation, necrosis, or fibrosis. Patients with cirrhosis usually have marked colloid shift and splenomegaly. Cross-sectional imaging studies of these patients may show ascites. With severe cirrhosis, the liver is small and irregular, and has a heterogeneous pattern of enhancement.

Bacterial Infection

Pathways for bacterial infections of the liver parenchyma include hematogenous inoculation via the PV, umbilical vein, or hepatic artery, extension from ascending cholangitis, and direct inoculation due to trauma or surgery. Umbilical vein catheterization is a predisposing factor for many instances of pyogenic liver infection in neonates. Infants can also develop liver infection due to Escherichia coli bacteremia. Most bacterial liver infections in older children are associated with an immunodeficiency state or biliary tract obstruction. Spread from an intra-abdominal infectious process, such as appendicitis, is responsible for hepatic infection in some patients.

The clinical manifestations of bacterial liver infection are often nonspecific. Potential findings include fever, leukocytosis, hepatomegaly, and upper abdominal pain. Liver function tests are usually normal. Staphylococcus aureus is the most common causative organism; infections with gram-negative organisms and anaerobic organisms can also occur. Neonates with bacterial liver infection often are jaundiced. The most common infectious agents involved in neonatal bacterial liver infection include E coli, Listeria monocytogenes, Streptococcus species, and S aureus.

The characteristic imaging feature of bacterial liver infection is the presence of 1 or more hepatic abscesses. Abscesses are more common in the right lobe than the left. Prior to the development of a true abscess, imaging studies show relatively nonspecific hepatomegaly and alterations in the parenchyma due to inflammation.⁴¹

Sonography usually shows a hepatic abscess as a moderately hypoechoic lesion that is surrounded by a zone of edematous parenchyma. Purulent material usually results in scattered internal echoes; a purely anechoic abscess is uncommon. Occasionally, there are echogenic foci within the abscess due to gas bubbles. Early in the course, a liver abscess often lacks the thick irregular wall that is typical of abscesses in other organs. The wall increases in thickness with maturation. Septations and fluid levels are sometimes visible. Prior to the formation of an abscess, sonography demonstrates a focus of hepatic bacterial infection as a hypoechoic lesion without an anechoic center and lacking acoustic enhancement. Sonography is sometimes equivocal in distinguishing a solid from a purulent lesion.

CT is more sensitive than sonography for the detection of bacterial liver infection. An abscess is demonstrated as a focus that lacks contrast enhancement (Figure 41-19). A mature abscess has a thick peripheral wall that undergoes contrast enhancement. In some cases, there is a cluster of small abscesses. The attenuation characteristics of the abscess vary with the nature of the contents, such as, pus, debris, or hemorrhage. In about one-third of patients with a pyogenic liver abscess, dynamic CT shows a low-attenuation central area surrounded by a high-attenuation ring that is surrounded by a lower attenuation peripheral zone; this is termed the “double target sign.” Gas is occasionally present in a hepatic abscess. As with sonography, the CT findings do not consistently allow differentiation of a round focus of bacterial hepatitis from a debris-laden abscess.⁴²

A liver abscess typically produces low signal intensity on T1-weighted MR images and high signal intensity on T2-weighted images. The wall produces intermediate signal intensity. Occasionally, proteinaceous material within the abscess causes elevation of T1 signal intensity. There is usually prominent contrast enhancement in the tissue surrounding the abscess. Delayed images sometimes show diffusion of gadolinium into the cavity.

Epstein-Barr Virus Infection

Hepatomegaly occurs in 10% to 30% of patients with infectious mononucleosis, and splenomegaly in approximately 50%. Less than 5% develop jaundice. Potential biliary manifestations of Epstein-Barr virus infection include cholecystitis, GB wall thickening, and GB hydrops (Figure 41-20).^43,44

Fungal Infection

Children with a fungal infection of the liver nearly always have a predisposing immune compromising condition. Candida organisms are responsible for most hepatic fungal infections; other potential infections include aspergillosis, mucormycosis, cryptococcosis, and histoplasmosis. In most instances, hepatic involvement occurs in the setting of disseminated fungal disease, with the liver and spleen representing common sites of involvement.

Fungal lesions of the liver are usually hypoechoic on sonography. There are 4 classic sonographic patterns of a hepatic abscess due to Candida infection. (1) The most common is a uniformly hypoechoic lesion, representing fibrous tissue. (2) Early in the course of the disease, a “wheel-within-a-wheel” pattern may occur. This consists of an outer hypoechoic zone (fibrosis) surrounding an echogenic zone (inflammatory cells) and a central hypoechoic nidus (necrosis). (3) The bull’s-eye lesion consists of a central hyperechoic area that is surrounded by a zone of decreased echogenicity. The central echogenic focus represents inflammatory cells. (4) Late in the course of the disease, a fourth pattern consisting of echogenic foci (scars ± calcification) with a variable degree of posterior acoustic shadowing may be present.

The most common CT appearance of fungal hepatic abscesses is that of multiple low-attenuation lesions of variable size, scattered throughout the liver. Lesion size is quite variable between patients. A “salt-and-pepper” pattern may occur when there are innumerable tiny abscesses. In most instances, the abscesses are most conspicuous on contrast-enhanced images. There are, however, unusual instances in which the reverse is true. In some patients, 1 or more of the abscesses contain a central high-attenuation focus, representing hyphae. Rim enhancement is sometimes present. Rarely, unenhanced or enhanced CT scans demonstrate a low-attenuation rim of edema surrounding the abscess cavity, producing a target lesion. Late in the course of the disease, calcifications at the site of a healing abscess are sometimes visible on CT. Calcification is particularly common with fungal infections in chronic granulomatous disease patients.

Candida abscesses of the liver usually are hyperintense to normal parenchyma on T1-weighted MR images. T2-weighted sequences show prominent signal intensity due to increased fluid within the abscess as compared to normal liver. The adjacent reactive edema is of intermediate T2 signal intensity. Most often, there is diffuse enhancement on early images and peripheral rim enhancement on delayed images.

The scintigraphic findings of hepatic fungal infection are generally indistinguishable from those of other focal or multifocal liver lesions. Sulfur colloid scintigraphy shows either hepatomegaly and colloid shift or focal defects. Extensive microabscesses may result in uniform decrease in parenchymal tracer accumulation; larger lesions produce discernible focal defects.

Liver infections due to blastomycosis, cryptococcosis, and histoplasmosis often lead to granuloma formation. The original infection is sometimes asymptomatic or associated with nonspecific symptoms. A granuloma is a localized collection of chronic inflammatory cells. Granuloma formation can also occur with nonfungal infections (bacterial, parasitic, and viral), in response to drugs, and in various systemic disorders (e.g., chronic granulomatous disease, Hodgkin lymphoma, sarcoidosis, and connective tissue disorders). Sonography typically demonstrates a granuloma as an echogenic lesion with a surrounding hypoechoic halo. Focal echogenic calcifications are common as residual sequelae (Figure 41-21). Liver granulomas are hypoattenuating on contrast-enhanced CT in the acute phase of the disease. Calcified scarring is often present as a residual finding. Caseating granulomas produce intermediate to high signal on T2-weighted MR images, low signal on T1-weighted images, and variable contrast enhancement. Noncaseating granulomas are usually of intermediate signal intensity on both T1- and T2-weighted sequences, and have prominent enhancement on arterial phase images that persists on late phase images.

Cat Scratch Disease

Cat scratch disease is a bacterial infection caused by the gram-negative bacillus Bartonella henselae. This is most often a self-limited illness limited to regional lymph nodes. Patients with disseminated infection can develop hepatitis or hepatic granulomas. Hepatic granulomas in these patients appear on imaging studies as multiple focal parenchymal liver lesions. They are usually hypoechoic on sonography and hypoattenuating on contrast-enhanced CT. Larger lesions sometimes have prominent peripheral enhancement. The lesions may accumulate radiogallium or ¹¹¹indium-labeled leukocytes. Coexistent splenic lesions are present in some patients.⁴⁵

Tuberculosis

The liver is a common site of involvement in patients with disseminated tuberculosis. This form of tuberculosis is most common in infants and malnourished or immuno-suppressed children and adults. The clinical onset usually is approximately 2 to 6 months after the primary infection. In patients with miliary tuberculosis, CT shows multiple low-attenuation parenchymal liver lesions, usually 1 to 2 cm in size.

Patients with tuberculosis can also develop isolated granulomas. On sonography, these are echogenic lesions that usually are less than 1 cm in size. Frequently, a hypoechoic halo surrounds the lesion. The granuloma is hypoattenuating to normal liver on contrast-enhanced CT. In the healing phase, punctate calcifications are common.

Parasitic Infections

Echinococcosis

Echinococcosis (hydatid disease) is caused by infection with Echinococcus granulosus (most common), E multilocularis, or E vogeli (rare). Canids (e.g., dogs, wolves, and fox) are the definitive hosts of hydatid disease. Humans are occasional intermediate hosts in the life cycles of these parasites. Tapeworms in the intestine of the definitive host produce eggs, which are excreted in the feces. Humans develop infection after accidental ingestion of eggs. The parasites penetrate the bowel mucosa and predominantly pass through the portal circulation to the liver. The host defense mechanisms destroy most embryos, but those that survive develop within the liver or other tissue such as the lung.^41,46

The larvae of E granulosus develop within the liver into cysts that, after 5 to 6 months, are approximately 10 mm in diameter. A hydatid cyst is composed of an outer pericyst produced by the host response and 2 inner layers produced by the parasite: a middle laminated acellular layer and a thin inner germinal layer. The cysts contain clear fluid, sometimes with sedimentary precursors to the scolices of adult worms (hydatid sand). The infection stimulates an inflammatory and fibroblastic reaction in the surrounding hepatic parenchyma. Approximately 70% of affected patients have a single cyst. Daughter cysts sometimes form around the main lesion; multiloculated cysts may develop. Most symptoms are due to mass effect: pain, abdominal distention, and a palpable mass. Rupture of a cyst may lead to an acute clinical presentation, with biliary colic, jaundice, and eosinophilia. Approximately one-fourth of patients diagnosed with E granulosus hydatid disease are children. E granulosus is most common in areas of the world where sheep and cattle are raised, including regions of the Mediterranean, Australia, New Zealand, Argentina, Utah, Arizona, New Mexico, and California; in Africa, this disorder is endemic in Uganda and Kenya.

Hydatid cysts due to E granulosus infection are detected easily with sonography. There are 1 or more well-defined anechoic cysts, frequently with adjacent smaller cysts. Internal septations may be present due to formation of daughter cysts or internal collapse of a ruptured laminated membrane. In some cases, internal debris results in a variable increased echogenicity. Shadowing due to cyst wall calcification is an occasional finding. Hydatid cyst rupture may occur in 3 forms: (1) contained, when the endocyst ruptures and the contents remain within the pericyst; (2) communicating, when the cyst contents escape into the biliary radicles; and (3) direct, when both the endocyst and the pericyst tear, allowing the contents to spill into the pleural or peritoneal spaces. Potential sonographic findings of cyst rupture include increased echogenicity of the cyst contents, visualization of echogenic or nonechogenic daughter vesicles, echogenic fragmented membranes in the biliary system, and direct visualization of a communication between a cyst and a bile duct. If there is internal collapse of the ruptured middle membrane of the cyst, floating membranes or a water lily sign may be present.

The CT appearance of a hydatid cyst is often identical or similar to that of a simple hepatic cyst: a low-attenuation nonenhancing mass with a well-defined wall. The attenuation characteristics of the contents vary somewhat between patients. Progressive disease can lead to calcification, membrane detachment, or daughter cysts. Most often, there is a single dominant mother cyst that is surrounded by smaller daughter cysts. The attenuation values of the daughter cysts are usually lower than those of the mother cyst. CT findings of hydatid cyst rupture include interruption of the cyst wall, fluid–fluid levels, and intrabiliary hydatid components.⁴²

On MRI, hydatid cysts due to E granulosus are usually hypointense on T1-weighted images and hyperintense on T2-weighted images. Occasionally, the cyst wall can be discerned as a hypointense rim. The rim often enhances with IV contrast. Wall calcification, when present, is hypointense. The contents of daughter cysts are usually isointense or minimally hypointense to the mother cyst on T1-weighted images. A detached membrane may be visualized as a thin intraluminal structure. With membrane detachment, the pericyst becomes visible as a peripheral low signal intensity structure on T2-weighted images.⁴⁷

Hydatid liver disease due to E multilocularis differs in several respects from that due to E granulosus. Well-defined membranes usually do not form, and the disease tends to infiltrate large areas of the liver. The growth of the larval tissue may resemble that of a malignant tumor; this is termed alveolar hydatid disease. Destruction of liver tissue may slowly progress to involve contiguous structures, such as the hepatic veins, PV, IVC, and biliary tract. Central necrosis is common as the mass enlarges. Hematogenous dissemination can result in infections of the heart, lungs, or brain.⁴⁸

Foxes, dogs, and other canids are the primary hosts in the life cycle of E multilocularis. Humans are occasional intermediate hosts after exposure by handling infected animals or ingesting contaminated food or water. Common presenting clinical features of this disorder include hepatomegaly and jaundice. Most patients with this infection come to clinical attention as adults. The imaging appearance of E multilocularis liver disease is distinct from that of the classic hydatid cyst produced by E granulosus. Sonography usually shows a solid, heterogeneous echogenic liver mass with multiple hyperechoic nodules. The border between the lesion and adjacent normal liver parenchyma is ill-defined. Occasionally, necrosis results in an irregular cystic mass or a mixed lesion that contains both hyperechoic nodules and cystic areas. Bile duct dilatation is frequently present.

CT in cases of E multilocularis liver disease also shows an aggressive, infiltrative abnormality, which may be indistinguishable from that of a malignant tumor. Invasion of adjacent structures can occur. The lesions are usually hypoattenuating to normal liver on contrast-enhanced images and the enhancement character is often heterogeneous. Ill-defined cystic areas of necrosis may be present, particularly with a large lesion. Calcifications are visible in most cases (65%).⁴⁹

Fibrosis and parasitic tissue produce relatively low signal intensity on T1- and T2-weighted MR sequences. There is usually no or minimal contrast enhancement; this is an important feature in the differentiation from a neoplasm. Cystic and necrotic areas are hyperintense on T2-weighted images. Large areas of calcification, when present, result in hypointense foci.^47,50

Amebiasis

Amebiasis refers to infection with the protozoan Entamoeba histolytica. This disorder is common in the developing world. The typical cause of amebiasis is the ingestion of contaminated water or food. Hepatic amebiasis occurs after invasion of the bowel wall by trophozoites and vascular dissemination via the portal venous system. Liver abscess is the most common extraintestinal manifestation of amebiasis. Multiple abscesses occur in many of these patients.^51,52

The major clinical consequences of infection with E histolytica are amebic dysentery (most common in children) and amebic liver abscess (most common in young adult males). Some infected individuals are asymptomatic, and serve as disease carriers. Potential clinical findings of amebic liver abscess include fever, tender hepatomegaly, and abdominal distention. Diarrhea is sometimes present. Jaundice occurs in approximately 10% of patients. Laboratory studies may demonstrate a normocytic-normochromic anemia, erythrocyte sedimentation rate elevation, and leukocytosis.⁵³

The sonographic findings of E histolytica infection of the liver vary with the stage of the disease. Early in the course, a focus of infection often has a solid character and is hyperechoic relative to normal parenchyma. The more characteristic hypoechoic features of a true abscess soon develop. The mass usually has a round or oval configuration. At high-gain settings, fine homogeneous low-level echoes are often visible throughout the lesion. Acoustic enhancement is usually present. These lesions tend to be contiguous with the liver capsule.

Early in the course of amebic liver abscess formation, the lesion usually has a poorly defined, hypoechoic wall. A fine echogenic rim subsequently develops, and echogenic projections may be visible in the abscess cavity. With a favorable response to medical therapy, the wall eventually becomes thick and well defined, and the echogenicity of the cavity decreases. Compared to pyogenic abscesses, amebic liver abscesses more frequently have well-defined margins, a peripheral halo, an anechoic center, and multiple lesions in contiguity. Sonography is also useful for detecting complications of an amebic liver abscess; potential findings include spread within the liver in the form of multiple new abscesses, perforation of the diaphragm and extension into the thorax, intraperitoneal rupture, and biliary obstruction.

The CT appearance of amebic liver abscess is somewhat variable. Most often, 1 or more round or oval low-attenuation lesions are demonstrated. The margins may be smooth or nodular. Internal septations are less frequent than in pyogenic abscesses. Contrast enhancement of the cyst wall is common. A low-attenuation rim of edema is sometimes present at the peripheral margin of the lesion. In some patients, contrast-enhanced images show alternating rings or halos of varying attenuation values surrounding the lesion. Images should be carefully inspected for evidence of extrahepatic extension (pleural effusion, perihepatic fluid, gastric or colonic involvement, or retroperitoneal extension).

The MR appearance of an amebic liver abscess is that of a sharply circumscribed heterogeneous mass. The lesion is generally hypointense to normal liver on T1-weighted images and hyperintense on T2-weighted images. Debris within the cyst cavity produces a heterogeneous appearance. The margins of the abscess are usually well defined. T2-weighted images may also demonstrate a larger region of hyperintensity extending from the margins of the abscess to the liver surface, corresponding to edema in normal liver tissue. With appropriate medical therapy, the cyst contents become homogeneously hypointense on T1-weighted images. An additional sign of successful therapy is the appearance of concentric rings at the margin of the lesion, due to maturation of the abscess wall.^41,54

Ascariasis

Ascariasis is a helminthic infection caused by the roundworm Ascaris lumbricoides. This disorder is endemic throughout most of the world; an estimated 1.4 billion persons are infected with this organism. The majority of infections occur in the developing countries of Asia and Latin America. However, approximately 4 million people in the United States are infected; many are immigrants from developing countries. The prevalence of this infection is higher in children than in adults, with a peak age of symptomatic disease of 3 to 8 years. Symptomatic ascariasis is restricted to patients with a heavy worm load; an estimated 1.2 to 2 million such cases, with 20,000 deaths, occur in endemic areas per year. Recurring infections in children cause growth retardation and reduced cognitive function.

The adult roundworm primarily resides in the jejunum. Extension of larva into the liver generally occurs hematogenously through the PV; adult worms can gain access to the biliary tree via the ampulla of Vater. Intrabiliary worms cause bile duct obstruction and symptoms of biliary colic. Bile duct rupture is a rare complication. The clinical manifestations include biliary colic and manifestations of acute cholecystitis, acute cholangitis (jaundice), acute pancreatitis, and hepatic abscess. Biliary system calculi can develop in these patients.

Diagnostic imaging studies of patients with biliary ascariasis show bile duct dilation that varies in severity between patients. Demonstration of worms or fragments of organisms in the biliary tree suggests the correct diagnosis. Sonography is usually the most sensitive imaging technique. In transverse orientation, a worm within a bile duct may produce a bull’s-eye appearance. On longitudinal images, the worm appears as a long tubular echogenic object, sometimes with a thin central hypoechoic line that represents the digestive tract. Real-time imaging may show movement of the worms. Ductal dilation and intraluminal objects may also be demonstrated in the pancreatic system.^55–57

Schistosomiasis

Schistosomiasis (bilharziasis) is a granulomatous disease that is due to infection with a parasitic blood fluke. At least 200 million individuals worldwide are infected with schistosome species. The major clinical manifestation of liver involvement is hepatomegaly. With progression of disease, periportal fibrosis and granuloma formation occur in response to trapped ova in the presinusoidal regions; this causes portal obstruction. Manifestations of portal hypertension and cirrhosis may develop at this stage of the disease.^58–60

In patients with infection due to Schistosoma japonicum, sonography shows echogenic branching septa that separate lobules of normal appearing parenchyma, producing a mosaic or fish-scale network pattern. The liver surface is irregular. CT shows septal enhancement and calcifications. Liver sonography in patients with Schistosoma mansoni infection shows prominent periportal echogenicity due to fibrosis. The periportal fibrosis in these patients is demonstrated with CT as enhancing rings. Calcifications are not a feature of this form of schistosomiasis.⁶¹

Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis is established by the clinical and immunological features, characteristic liver histopathology, and the exclusion of potential mimicking conditions such as the viral hepatitis, Wilson disease, α₁-antitrypsin deficiency, drug-induced hepatitis, and hemochromatosis. The typical histological features include an interface hepatitis pattern with piecemeal necrosis, a lymphoplasmacytic cell infiltrate, and (often) fibrosis. Many affected patients progress to cirrhosis, sometimes requiring liver transplantation. Regenerative liver nodules sometimes occur in patients with autoimmune hepatitis; these may appear as prominently enhancing foci on CT.^62,63

Biliary System

Acute suppurative cholangitis (ascending cholangitis) is a potentially life-threatening condition that is nearly always associated with biliary tract obstruction. The underlying biliary obstruction in these patients can be related to a congenital anomaly, choledocholithiasis, or prior biliary tract surgery (e.g., liver transplantation). The clinical findings include right upper quadrant pain, fever, cholestatic jaundice, and leukocytosis. The infectious agents in these patients are usually gram-negative bacteria. A chronic recurrent form of suppurative cholangitis can also occur.

Sonography of the child with suppurative cholangitis typically demonstrates dilation and irregularity of the bile ducts, although a lack of bile duct dilation does not exclude the diagnosis. Echogenic debris is often visible within the biliary system. In some patients, there is thickening of the common bile duct wall. Sonography may show liver abscesses and pneumobilia in patients with severe disease (Figure 41-22).

Dynamic contrast-enhanced CT imaging can be useful for the evaluation of a patient with suspected acute cholangitis. Early contrast-enhanced images (within approximately 30 seconds of initiation of contrast injection) often have a heterogeneous pattern of parenchymal enhancement; this can be nodular, patchy, wedge-shaped, or geographic in character. This finding apparently reflects increased arterial blood flow in the dilated peribiliary plexus. Bile duct wall thickening and irregularity are sometimes present. There is increased attenuation of the bile due to debris in some patients. With severe disease, the intrahepatic bile ducts are dilated and markedly irregular; liver abscesses and pneumobilia may be present as well.⁶⁴

Hepatobiliary scintigraphy in patients with acute suppurative cholangitis usually shows relatively preserved extraction of radiopharmaceutical by the liver, but delayed or poor excretion into the bile ducts. The bile ducts may appear dilated and irregular. An abscess of sufficient size results in a focal parenchymal defect during the hepatocyte phase; if the abscess communicates with the bile ducts, tracer may eventually accumulate in the lumen.

An important role for diagnostic imaging studies in patients with suppurative cholangitis is the detection of an underlying biliary obstruction such as a calculus or stricture. Sonography may demonstrate a stone in the common bile duct; however, because pneumobilia is common in patients with suppurative cholangitis, care must be exercised in the differentiation between a calculus and gas in the duct. MRCP often allows demonstration of choledocholithiasis or a biliary stricture; the underlying cholangitis results in findings such as biliary tract dilation, ductile irregularity, intrabiliary debris, and parenchymal edema or abscess. In some patients, percutaneous or endoscopic cholangiography is required for accurate diagnosis of an obstructing lesion. Percutaneous drainage procedures are also helpful for treating the primary infection in selected patients with suppurative cholangitis.

Recurrent pyogenic cholangitis (oriental cholangiohepatitis) is an idiopathic biliary tract disease that is common in portions of Southeast Asia. Parasitic infections or nutritional deficiencies may be implicated in the pathophysiology. Culture of the bile from these patients usually demonstrates the presence of enteric bacteria. The intrahepatic and extrahepatic bile ducts in patients with recurrent pyogenic cholangitis are dilated and filled with pigmented stones and purulent material. Imaging studies show marked bile duct dilation, sludge in the intrahepatic ducts, choledocholithiasis, biliary strictures, prominent enhancement of ductal walls on CT, and prominent periportal echogenicity on sonography.⁴²

Children with AIDS are at risk for cholangitis due to an opportunistic infection. The most commonly involved organisms include cytomegalovirus, HIV, and Cryptosporidium. Imaging studies of these children usually show relatively mild bile duct dilation. Some degree of bile duct wall thickening is usually present; the GB wall may also be thickened. One or more areas of irregular narrowing of the common hepatic or common bile ducts are common.⁶⁵

Pylephlebitis

Pylephlebitis refers to septic thrombophlebitis of the portal venous system. This is a rare complication of an intra-abdominal inflammatory disease such as appendicitis, diverticulitis, pancreatitis, or Crohn disease. This serious complication can be fatal. Potential findings on sonography include echogenic material in the PVs, portal venous gas, liver abscesses, and splenomegaly. Doppler evaluation demonstrates slow, absent, or reversed flow in the main PV. CT and MR demonstrate clot in the mesenteric and/or PVs (Figure 41-23).^66–68

Clinical Presentations: Portal Hypertension

Elevation of portal venous pressure can occur in association with a wide variety of localized and systemic disorders. There are 3 general types of portal hypertension, based on the level of predominant obstruction to portal venous flow. Obstruction of the extrahepatic portal venous system, termed prehepatic or presinusoidal portal hypertension, accounts for the majority of pediatric cases. This is most often due to occlusion or stenosis of the main PV. Parenchymal liver lesions, such as cirrhosis, can cause interference with portal venous perfusion, thereby leading to intrahepatic or sinusoidal portal hypertension. Posthepatic or postsinusoidal portal hypertension refers to obstruction at the level of the intrahepatic venules, larger hepatic veins, or IVC.

The clinical manifestations of portal hypertension are largely determined by the severity and chronicity of the underlying disorder and by the level of portal venous obstruction. Ascites and splenomegaly are common in these patients. Manifestations of hypersplenism occur. Portosystemic collateral vessels develop in most patients with portal hypertension. Superficial collaterals can sometimes be identified clinically, for example, distended veins in the abdominal wall. Hemorrhage from esophageal collaterals (varices) can lead to hematemesis and/or anemia. Other potential sources of hemorrhage in these patients are portal hypertensive gastropathy or varices in the stomach, duodenum, or rectum. If there is substantial shunting, hepatic encephalopathy can ensue. Other potential findings include hemorrhoids and caput medusae.

Although there are no noninvasive techniques that directly measure the portal venous pressure, various imaging findings help to establish the diagnosis of portal hypertension and characterize the underlying pathology. Cross-sectional imaging with sonography, CT, or MR serves to determine patency of the major PVs and the draining systemic veins. Obstruction can be intrinsic (thrombosis) or extrinsic (compression by a tumor). These techniques also allow accurate determination of liver or spleen morphology. Hepatic parenchymal disease typically leads to alterations in the echogenicity, attenuation, or signal of the liver.

The PVs proximal to the site of obstruction usually become enlarged in patients with portal hypertension. However, the severity of this finding varies substantially between patients. Factors that affect the portal venous size include the location of the obstruction, the degree of decompression via collateral channels, and the chronicity of the obstruction. An additional potential finding on imaging studies of children with portal hypertension is enlargement of portosystemic collateral channels. The collateral pathways can be divided into 2 types: tributary and developed. Tributary collaterals are vessels that are patent in normal individuals and drain into the portal system; they become enlarged and exhibit retrograde flow in the presence of portal hypertension. Examples of tributary collaterals include mesenteric veins, short gastric veins, and left gastric veins; esophageal varices arise from tributary collateral flow. Developed collateral vessels are recanalized vessels that do not normally drain into or from the portal system in postnatal life. Examples include paraumbilical, splenorenal, and splenoperitoneal collaterals.

Doppler sonography is the most useful noninvasive technique for the characterization of the dynamics of portal venous flow in children with suspected portal venous hypertension. Doppler studies allow evaluation of flow velocities in PVs, hepatic arteries, hepatic veins, and portosystemic collateral vessels. Portal hypertension generally causes diminished velocity of blood flow in the main PV. PV velocity of lower than 20 cm/s is generally considered abnormal. An additional finding is increased PV pulsatility. This refers to variation in portal venous flow velocity during respiration, which becomes more pronounced in patients with portal hypertension. The effect is magnified by breath holding or the Valsalva maneuver, during which blood flow may temporarily cease or reverse. With severe portal hypertension, Doppler studies may demonstrate hepatofugal flow. The direction and velocity of blood flow sometimes vary within intrahepatic portal venous branches because of regional differences in hepatic parenchymal disease, intrahepatic arteriovenous shunting, or portosystemic collateral flow.^69–72

In addition to alterations in portal venous flow, portal hypertension can result in changes in the dynamics of hepatic arterial flow and hepatic venous drainage. In normal individuals, the PV accounts for approximately 75% of hepatic perfusion. When portal venous perfusion of the liver is interrupted, hepatic arterial flow increases. This “buffer response” protects the liver from manifestations of ischemia despite occlusion of the PV. Doppler studies in these patients may show manifestations of a relative increase in hepatic arterial flow. However, parenchymal liver disease can lead to diminished diastolic flow because of resistance to arterial perfusion; this is demonstrated as increased Doppler waveform pulsatility. Patients with portal hypertension also tend to have dampened hepatic venous waveforms due to diminished portal venous perfusion of the liver and decreased hepatic parenchymal compliance.

Sonography also serves to identify portosystemic collateral vessels and to characterize the direction and velocity of blood flow within these channels. The presence of esophageal varices is associated with thickening of the lesser omentum between the aorta and the left lobe of the liver. A lesser omental thickness in this region that measures more than 1.7 times the diameter of the aorta supports the diagnosis of portal hypertension (in the absence of other known causes of soft tissue thickening in this area, such as obesity or lymphadenopathy).⁷³ Careful evaluation of the splenic vein should be performed in patients with suspected portal hypertension. Flow within the splenic vein may slow or reverse in the presence of substantial collateral flow. In patients with paraumbilical collateral flow, sonography may demonstrate more pronounced hepatopetal flow in the left PV than in the right, due to shunting of blood from the left PV into the collateral channel. In the presence of a splenorenal shunt, the left renal vein may be enlarged and have elevated flow velocity. With extrahepatic PV obstruction, portoportal collateral vessels are demonstrated with sonography as a network of tortuous channels in the porta hepatis; there is hepatopetal blood flow in these vessels. Portoportal collaterals can result in thickening of the GB wall.⁷⁴

Angiographic techniques for evaluation of the portal venous system include intraarterial splenoportal and mesentericoportal digital subtraction catheter angiography, CT angiography, and MR angiography. Splenoportography and transhepatic portography are rarely utilized invasive techniques that provide direct measurement of portal venous pressure and angiographic assessment of portal venous flow dynamics. Important angiographic findings in patients with portal hypertension include PV size and patency, the presence of thrombus within the PV, and the character of portosystemic collateral vessels. The determination of transhepatic wedge pressures via a catheter introduced into the hepatic veins provides an estimation of portal venous pressure. Normal portal venous pressure is approximately 8 mm Hg. The pressure gradient between the PV and the IVC is normally lower than 5 mm Hg. With severe portal hypertension and hepatofugal flow, the PV does not opacify on angiography performed via injection of the superior mesenteric artery; there is reversal of flow on hepatic wedge venography.^75–78

Children with portal hypertension are often treated conservatively. Bleeding esophageal varices can be treated with endoscopically-guided sclerotherapy. In patients with recurrent or intractable hemorrhage, portal venous pressure can be decreased by a transjugular intrahepatic portosystemic shunt (TIPS) or an open surgical portosystemic shunt. Surgical shunts include splenorenal (side-to-side without splenectomy or end-to-side with splenectomy), mesocaval (end-to-side cavomesenteric), portacaval, and mesoatrial anastomoses.⁷⁹ Preoperative planning is facilitated by demonstration of the vascular anatomy with MRI, CT angiography, or transarterial portography. Sonography is the main imaging technique for monitoring the patency of these shunts. Patency of a surgical portosystemic shunt can usually be visualized directly with ultrasound. Indirect signs of shunt patency include decrease in the thickness of the lesser omentum, diminution of collateral vein sizes, decrease in the diameter of the PV, increase in the diameter of the IVC, and hepatofugal flow in the PVs. Angiography and CT angiography provide supplemental information for selected cases. Transcatheter therapy is useful for some patients with shunt malfunction.⁸⁰

A TIPS is a stented tract between an intrahepatic PV and a hepatic vein. The stent is visualized sonographically as a tubular structure with echogenic walls. The sonographic features of an appropriately functioning patent TIPS shunt are hepatofugal flow in PV branches and nonpulsatile or minimally pulsatile flow in the stent with peak velocities of 75 to 200 cm/s. Thrombosis is indicated by absence of flow within the shunt. With stenosis of the shunt or of the draining hepatic vein, Doppler ultrasound shows peak shunt velocities of less than 90 or more than 220 cm/s, decrease in shunt velocity of more than 40 cm/s or increase of more than 60 cm/s on sequential studies, reversed flow in the hepatic vein, or a change in flow direction in the right or left PVs.^81,82

Extrahepatic Portal Vein Obstruction

Extrahepatic PV obstruction is an important cause of noncirrhotic portal hypertension in children. The etiology is varied. An embryological cause (e.g., in utero thrombosis, extrinsic compression, or an intraluminal web) has been implicated in some cases. When obstruction occurs in utero or early in infancy, the affected portion of the PV may be replaced by a fibrous remnant. Potential acquired forms of extrahepatic PV obstruction include acute thrombosis (e.g., due to umbilical vein catheterization, trauma, hypercoagulable state, or liver transplantation) and extrinsic compression by a mass. Thrombotic pylephlebitis can occur in children as a complication of appendicitis.^83,84

Extrahepatic PV obstruction causes portal hypertension and the development of numerous portosystemic collateral vessels, including esophagogastric varices and enlargement of pericholecystic, pericholedochal, and pancreaticoduodenal veins. Some patients with extrahepatic PV obstruction develop distention of periportal collateral vessels to form a cavernoma, that is, cavernous transformation of the PV.⁸⁵ Most patients with extrahepatic PV obstruction are asymptomatic until manifestations of portal hypertension develop. Therefore, the diagnosis is frequently delayed for months or years after the initial etiological event. The potential clinical manifestations include variceal hemorrhage, portal biliopathy, hypersplenism, and growth retardation. Ascites occurs in some patients. Functional abnormalities of the liver tend not to occur until late in the process.

The imaging patterns offer clues to the etiology of PV obstruction. Obliteration of the intrahepatic PVs with no underlying medical or surgical cause is most often due to idiopathic hepatoportal sclerosis. Cavernous transformation of the main PV is most often a congenital lesion. Occlusion of the main PV in combination with occlusion of the superior mesenteric vein is the typical pattern in patients with portal hypertension due to abdominal sepsis. Widespread thrombosis throughout the portal system can occur due to various etiologies, including hypercoagulable states.

Abdominal radiographs of children with extrahepatic PV obstruction may be normal, or demonstrate splenomegaly. Occasionally, there is paravertebral soft tissue widening due to varices. Chest radiographs may show enlargement of the azygos vein in some of these patients. With advanced disease, manifestations of ascites are sometimes present.

Sonography is diagnostic for many children with extrahepatic PV obstruction. The most common finding is absence of a normal PV in conjunction with multiple tortuous collateral vessels in the porta hepatis. Doppler evaluation confirms that these collateral vessels represent portal veins rather than hepatic arteries. One or more bands of prominent echogenicity in this region may also be present, due to fibrosis. In those rare instances in which imaging is performed soon after a thrombotic event, sonography may demonstrate distention of the PV with echogenic clot.