The Icteric Patient: Hepatobiliary Imaging Explained

Introduction

Radiography and ultrasonography are the most well-established and most frequently used imaging modalities for diagnosing hepatic disease in veterinary medicine. The use of ultrasound and ultrasound-guided tissue sampling has now surpassed the use of survey radiography for the diagnosis of many liver diseases due to its broad availability and greater sensitivity. Every dog or cat with icterus should have abdominal radiography to screen the entire abdomen for not only the size, shape, and margination of the liver margins, but to obtain an overall impression of all organs for the presence of multi-organ disease or separate unrelated disease.

Radiography

Radiography is widely available and recommended in icteric dogs and cats suspected of having hepatic disease, but it is an insensitive method. Important to know are the anatomic locations of the gallbladder and bile duct, even though they are radiolucent. The enlarged gallbladder can appear as a smoothly marginated mass extending beyond the liver margin ventrally and to the right of the vertebrae on the VD image. Furthermore, it may contain mineralizations or gas. Mineralizations and gas within the biliary tree are also possible radiographic findings in icteric animals. Once pre-hepatic icterus is ruled out, hepatic parenchymal and biliary tree structure need to be investigated further with sonography. Radiographic contrast studies, such as intravenous cholangiocystography and percutaneous transhepatic cholangiocystography, for the diagnosis of biliary obstruction are described, but have not come into common use and have mostly been replaced by ultrasonography.

Ultrasound is complementary to the abdominal radiograph and provides a more detailed examination of the inner structure of the liver and surrounding organs. This update on hepatobiliary imaging does not include a description of survey and contrast radiographic examinations of the liver or the basic principles of hepatic sonography. The reader is referred to the many complete and excellent sources available on these topics.

Sonography

Diffuse parenchymal disease generally affects all lobes and may appear normal, iso-, or hyperechoic. Examples include cholangiohepatitis, diffuse prenodular (early) metastatic carcinoma or sarcoma, round cell neoplasia (lymphoma, mast cell disease, and histiocytic sarcoma), patchy or diffuse fatty infiltration, vacuolar hepatopathy, storage diseases (amyloidosis, copper), toxic hepatopathy, and early degenerative changes associated with micronodular hyperplasia and fibrosis. The overall accuracy of ultrasound as the sole criterion for discriminating among the categories of diffuse liver disease is <40% in dogs and <60% in cats. It is generally not possible to make a final diagnosis based on the combination of sonographic findings and biochemical and hematological data in dogs and cats with diffuse liver disease. Tissue sampling, preferably for histological examination, is required for a definitive diagnosis in most instances, even if the liver appears sonographically normal.

Vacuolar changes in the liver associated with lipidosis and steroid hepatopathy usually cause hepatomegaly in conjunction with diffuse hyperechogenicity and rounded borders. Inflammatory disease can be associated with diffuse hypoechogenicity. If acute hepatitis or cholangiohepatitis is present, the liver may appear to have high contrast, a hypoechoic parenchyma with pronounced hyperechogenicity of the portal veins. Chronic inflammation of the liver will usually result in hyperechoic or mixed echogenicities. When fibrosis or cirrhosis is present, the liver may be smaller and hyperechoic. If nodular hyperplasia develops, such as with vacuolar hepatopathy, the liver may appear more heterogeneous and nodular, such as in neoplastic disease. Other differentials for this pattern include amyloidosis in cats and dogs and hepatocutaneous syndrome in dogs.

Focal or multifocal changes in the liver parenchyma are easier to identify sonographically than diffuse changes. Hypo-, hyper-, and anechoic lesions are easy to identify, as they contrast better with the surrounding parenchyma. Therefore, cystic lesions are the easiest to detect, even when very small.

Anechoic cavitary structures in the liver can be due to necrosis, neoplasms, or cysts. Cyst structures generally have sharply defined borders, can be round or irregular in shape, and may even contain hyperechoic septa within them. Causes include congenital cysts, cavitations following trauma, biliary pseudocysts, or parasitism. Unfortunately, biliary cystadenomas and cystadenocarcinomas may appear similarly.

Neoplastic disease of the liver may manifest as diffuse, multifocal, or focal disease sonographically. Diffuse disease is usually due to round-cell neoplasia. Lymphoma, histiocytic sarcoma, and mast cell tumor are the most common neoplasms that may lead to diffuse changes that remain sonographically undetectable. Carcinomas tend to be diffusely spread throughout the liver and often lead to a mixed pattern.

Benign hyperplastic nodules are an extremely common finding in dogs, especially older ones. They are generally not more than 1 centimeter in diameter. Malignant nodules have a highly varied appearance and size. They may appear as hypo- or hyperechoic nodules, target lesions, or heterogenous ill-defined nodules. Hypoechoic nodules can be due to nodular hyperplasia, metastases, lymphoma, histiocytic sarcoma, primary neoplasia, necrosis, hematomas, and abscesses. For this reason, tissue sampling is critical to a definitive diagnosis, and the presence of hepatic nodules is not synonymous with malignancy. Hepatic target lesions have a positive predictive value for malignancy of 74% and this emphasizes the fact that histological type cannot be predicted by the presence of target lesions.

Hepatic abscessation occurs rarely in small animals and may appear similar to a primary tumor, granuloma, or hematoma due to their highly variable sonographic features. Sonographically, they may be round to irregular in shape with either a hypoechoic central region or of mixed echogenicity. Reverberation artifacts may be detected due to gas accumulations within the necrotic tissue. Focal peritonitis may be seen with abscessation and include free peritoneal fluid and focal hyperechoic mesentery.

Contrast-enhanced harmonic ultrasound (CEHU) is a new diagnostic option that allows assessment of the perfusion patterns of organs in a noninvasive manner. It requires the use of ultrasound probes and on-board software that are designed to receive and analyze the contrast signals. Second-generation phospholipid shell microbubbles containing Perflutren gas such as Definity® (Bristol-Myers Squibb) elicit harmonic frequencies at much lower acoustic powers than are necessary to generate tissue harmonics. The contrast agents are injected into a peripheral vein in small volumes and, because of their size, act as blood pool agents ideal for assessing organ perfusion.

Detection and characterization of liver nodules in dogs with CEHU have been the most commonly reported uses of the technique. The main difference between benign and malignant lesions is that during the portal and late phase all benign lesions, except cysts and thrombosed hemangiomas, exhibit iso-enhancement or slight hyperenhancement as compared to surrounding liver tissue. Malignant liver lesions exhibit hypoenhancement or do not perfuse at all, because the perfusion of malignant tumors is provided exclusively by arterial vessels and there is no portal venous supply. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CEHU for diagnosing benign vs. malignant liver nodules has been shown to be 100%, 94.1%, 93.8%, 100%, and 96.9%, respectively.

Biliary Disease

Biliary disease is divided into four main categories: biliary cystic disease, cholestasis, cholangitis, and diseases of the gallbladder (mucoceles, cholecystitis). Dogs and cats with icterus may have cholestasis due to intrahepatic or extrahepatic disease. Extrahepatic cholestasis can be caused by intraluminal obstruction (choleliths, mucinous cystic hyperplasia, sludge) or luminal constriction (neoplasia, inflammation) of the extrahepatic biliary tree or large intrahepatic ducts. Intramural biliary obstruction may occur secondary to biliary adenocarcinomas. Enlarged perihilar lymph nodes may also lead to ductal obstruction. The duodenum should also be examined for obstruction at the major duodenal papilla where both inflammatory and malignant diseases may be another source of obstruction. The common bile duct can be up to 3 mm in diameter in normal dogs and 4 mm in cats. These are evident as anechoic tubular structures at the porta hepatis (extrahepatic ducts) or throughout the parenchyma (intrahepatic ducts). Color Doppler ultrasound should be used to assess any anechoic tubular structure in the liver in order to differentiate biliary from vascular structures. Relief of the obstruction does not lead to immediate reduction in diameter of the dilated biliary ducts. The gallbladder may remain a normal size or be enlarged with extrahepatic bile duct obstructions. The presence of a normal-sized gallbladder should not eliminate the possibility of an obstruction.

Neutrophilic cholangitis or cholangiohepatitis is more common in cats than dogs. It is usually due to an ascending infection from the intestinal tract. Lymphocytic cholangiohepatitis is also common in cats. The two diseases cannot be distinguished sonographically in cats and require different treatment protocols. Therefore, it is important to perform tissue sampling to differentiate the two diseases. Sonographic features of cholangiohepatitis in cats include a diffusely hypoechoic liver parenchyma with prominent-appearing portal vascular structures. Included may be thickening of the gallbladder wall, bile duct wall, and increased amounts of sludge in the gallbladder. Intra- and extrahepatic dilation of the biliary tree may also be present. Similar findings to neutrophilic and lymphocytic cholangiohepatitis may occur in liver fluke infestation (family Opisthorchiidae in endemic regions). Because these diseases appear similarly and even may appear normal sonographically, tissue sampling is critical for a diagnosis.

Generalized gallbladder wall thickening can occur with cholecystitis, cholangiohepatitis, hepatitis, free peritoneal fluid, and hypoproteinemia. The wall may appear to have a "double"-layer appearance in these instances. Choleliths can occur, more commonly in dogs, and appear as hyperechoic structures of variable size, number, and shape that produce acoustic shadowing. They are not always associated with clinical signs and can be incidental findings, especially in older dogs. Both mineralized and non-mineralized material may also be found in the bile ducts.

Gallbladder mucoceles occur in dogs and are an important cause of icterus and obstructive disease. They are caused by cystic mucinous hyperplasia that leads to increased mucin production that distends the gallbladder and can eventually cause wall necrosis and rupture. Sonographically they have a varied appearance. The classical finding is that of a kiwifruit pattern of hyperechoic striations radiating from a central point. Sonographic signs of rupture include loss of the gallbladder wall continuity, hyperechoic surrounding mesentery and free peritoneal fluid. The sensitivity of ultrasonography for diagnosing gallbladder rupture is reported as 85%. The therapeutic dilemma as to whether to perform cholecystectomy arises when a gallbladder mucocele is identified sonographically, but without signs of rupture. It has been shown that they can transform into an acute clinical condition. A breed predilection has been suggested in Cocker Spaniels, Shetland Sheepdogs, and Miniature Schnauzers.

Cholecystitis is more frequent in cats than in dogs and is generally associated with bacterial infections. Because bile duct dilation and gallbladder wall changes may not occur in cats with neutrophilic cholecystitis, bile aspirations for cytological and bacteriological examination in cats may be necessary to confirm a suspected diagnosis and administer appropriate antimicrobials. Emphysematous cholecystitis may result from E. coli and Clostridium perfringens infections, which are gas-forming bacteria. It has also been associated with diabetes mellitus. Gas within the biliary tract, such as with mineralization, can be identified both radiographically and sonographically. In ultrasound, it appears as irregular or pinpoint-sized hyperechoic structures that produce reverberation artifacts. The presence of gas in the gallbladder or liver parenchyma should alert the sonographer to the possibility of cholecystitis, cholangitis, choledochitis, or abscess formation.