DOI: 10.1148/rg.244035719
RadioGraphics 2004;24:937-955
© RSNA, 2004
The Infected Liver: Radiologic-Pathologic Correlation1
Koenraad J. Mortelé, MD,
Enrica Segatto, MD and
Pablo R. Ros, MD
1 From the Division of Abdominal Imaging and Intervention, Department of Radiology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115. Received July 31, 2003; revision requested October 3 and received January 2, 2004; accepted January 5. All authors have no financial relationships to disclose. Address correspondence to K.J.M. (e-mail: kmortele@partners.org).
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Abstract
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Recent technologic advances have significantly enhanced the role of imaging in the detection, characterization, and management of infectious diseases involving the liver. In addition, imaging-guided percutaneous drainage has greatly improved the clinical treatment of patients with focal liver abscess. Infectious liver diseases can be accurately evaluated with ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging. Characteristic changes in US echogenicity, CT attenuation, or MR imaging signal intensity and typical enhancement patterns can contribute to the diagnosis of specific infectious diseases, including abscesses, parasitic diseases, fungal diseases, granulomatous diseases, viral hepatitis, and other less common infections. CT is particularly helpful in revealing the presence of calcifications and gas and in detailing the enhancement pattern. The multiplanar capability of MR imaging and its sensitivity to small differences in tissue composition increase its specificity for certain hepatic infections, including hydatid cyst and candidiasis. Radiologic findings may be sufficient to obviate aspiration or histologic examination, although in most instances they are less specific. Nevertheless, imaging findings taken together with appropriate clinical information may provide the most likely diagnosis, even if biopsy is sometimes required for confirmation.
© RSNA, 2004
Index Terms: Amebiasis, 761.2071 • Liver, abscess, 761.21 • Liver, CT, 761.1211 • Liver, cysts, 761.311 • Liver, diseases, 761.20, 761.2083, 761.21, 761.291 • Liver, echinococcosis, 761.2083 • Liver, infection, 761.20, 761.2083, 761.21, 761.291 • Liver, MR, 761.1214 • Liver, US, 761.1298
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LEARNING OBJECTIVES FOR TEST 1
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After reading this article and taking the test, the reader will be able to:
- Identify the most common imaging features of infectious liver diseases.
- Discuss the importance of clinical and biochemical information in characterizing these diseases.
- Describe the correlation between imaging findings and histopathologic findings in infectious liver diseases.
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Introduction
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Imaging plays a pivotal role in the work-up of patients with suspected liver infections. All cross-sectional techniques allow highly accurate detection of hepatic infections. Computed tomography (CT) is particularly helpful in revealing the presence of calcifications and gas and in detailing the enhancement pattern. In most cases, however, it is difficult to characterize necrotic infections with ultrasonography (US) and CT alone because the imaging findings are often nonspecific and may, therefore, mimic hepatic cysts or necrotic tumors. Magnetic resonance (MR) imaging can help detect liver abscesses at least as well as other cross-sectional methods. In particular, the multiplanar capability and sensitivity to small differences in tissue composition of MR imaging increase its specificity for certain hepatic infections, including hydatid cyst and candidiasis. Nonnecrotic infections also have a varied appearance but may have specific imaging characteristics. In most cases, however, radiologic findings are not sufficiently characteristic to help identify the type of infection, and aspiration or biopsy is needed for final diagnosis. In addition, access to epidemiologic and clinical information (eg, patient age, gender, clinical history, symptoms) remains extremely important for obtaining a more accurate presumptive diagnosis.
In this article, we review the radiologic and pathologic findings in a wide variety of infectious liver diseases and discuss the current role of imaging in the detection and characterization of these diseases, which include abscesses (pyogenic abscess, amebic abscess), parasitic diseases (Echinococcus granulosus [hydatid] cyst, E multilocularis cyst, schistosomiasis), fungal diseases (eg, candidiasis), granulomatous diseases (tuberculosis, histoplasmosis), viral hepatitis, and other less common infections (bacillary angiomatosis, human immunodeficiency virus [HIV] infection, cat-scratch disease).
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Hepatic Abscesses
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Pyogenic Abscess
The epidemiology of pyogenic abscess has changed significantly in the modern antibiotic era (1). Pyogenic abscesses, particularly when multiple, may be caused by hematogenous dissemination (of either gastrointestinal infection via the portal vein or disseminated sepsis via the hepatic artery), ascending cholangitis, or superinfection of necrotic tissue (2,3). A solitary hepatic abscess is often cryptogenic and has no clear-cut predisposing cause (1,4). Over one-half of liver abscesses are polymicrobic (4). Escherichia coli is the most common bacterium, but other anaerobic and aerobic organisms can be involved (5). Pyogenic abscesses demonstrate no sex predilection but most commonly involve middle-aged patients (6).
The clinical manifestations of pyogenic abscess are highly variable. Patients may present with high fever, rigors, and severe right-sided abdominal pain or may have clinically occult ("cold") abscesses that manifest only as weight loss and vague abdominal pain. Hepatic biochemical abnormalities are nonspecific, including slightly elevated total bilirubin and aminotransferase levels and hypoalbuminemia (2).
Early diagnosis and imaging-guided percutaneous drainage have markedly reduced both the mortality rates (from 40% of cases to 2%) and the need for surgery (1,7). Percutaneous drainage may not be necessary in cases of relatively small abscesses (<5 cm in diameter) because successful treatment may be achieved with antibiotics alone (7). Initial antibiotic regimens should include metronidazole until amebic abscess is ruled out serologically, cover the most common bacterial pathogens, and continue for a minimum of 6 weeks.
At gross examination, pyogenic abscesses appear as solitary or multiple lesions ranging from a few millimeters to several centimeters in diameter (Fig 1). At histopathologic analysis, the abscess cavity may reveal multiple locules, usually filled with thick, purulent material and lined by pale fibrous tissue. The fibrous cuff around the abscess is often a centimeter or more thick and gradually merges into the liver parenchyma. Microscopic sections of a pyogenic abscess show (depending on the stage) suppuration, liquefaction with presence of fibrinopurulent debris, and fibrosis (Fig 2). The edges of the cavities are composed of a chronic inflammatory infiltrate consisting of epithelioid macrophages, lymphocytes, eosinophils, and neutrophils (8).
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Figure 1a. (a) Pyogenic abscess. Photograph of a gross liver specimen shows a large, necrotic cavity with a perceptible fibrous wall in the right lobe (arrow). Note the yellowish pus content and inflammation of the adjacent liver parenchyma (arrowheads). (b) Pyogenic microabscesses. Photograph of a gross liver specimen obtained in a different patient shows multiple white nodules representing pyogenic microabscesses scattered throughout the parenchyma.
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Figure 1b. (a) Pyogenic abscess. Photograph of a gross liver specimen shows a large, necrotic cavity with a perceptible fibrous wall in the right lobe (arrow). Note the yellowish pus content and inflammation of the adjacent liver parenchyma (arrowheads). (b) Pyogenic microabscesses. Photograph of a gross liver specimen obtained in a different patient shows multiple white nodules representing pyogenic microabscesses scattered throughout the parenchyma.
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Figure 2a. Pyogenic abscess. (a) Low-power photomicrograph (hematoxylin-eosin [H-E] stain) shows an area of liquefaction necrosis. (b) Photograph of a gross liver specimen obtained in a different patient shows a zone of fibrosis (arrow) that has replaced the abscess cavity.
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Figure 2b. Pyogenic abscess. (a) Low-power photomicrograph (hematoxylin-eosin [H-E] stain) shows an area of liquefaction necrosis. (b) Photograph of a gross liver specimen obtained in a different patient shows a zone of fibrosis (arrow) that has replaced the abscess cavity.
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CT and US can reliably help detect more than 90% of pyogenic abscesses (2,9–11). Pyogenic abscesses may be classified as either microabscesses (<2 cm) or macroabscesses (larger lesions). Pyogenic microabscesses may appear as multiple widely scattered lesions similar in distribution to fungal microabscesses in immunosuppressed patients, or as a cluster of microabscesses that appear to coalesce focally (11,12). The diffuse miliary pattern of pyogenic microabscesses is caused by staphylococcal infection in patients with generalized septicemia and usually involves both the liver and spleen. The cluster pattern is associated with coliform bacteria and enteric organisms (11). It is likely that clustering of pyogenic microabscesses represents an early stage in the evolution of a large pyogenic abscess cavity.
At US, pyogenic microabscesses may manifest as either discrete hypoechoic nodules or ill-defined areas of distorted hepatic echogenicity. There may be little or no enhanced through transmission. At contrast material–enhanced CT, they appear as multiple small, well-defined hypoattenuating lesions. Faint rim enhancement and perilesional edema can be seen (Fig 3), findings that help differentiate them from hepatic cysts. Large pyogenic abscesses demonstrate a wide range of US and CT appearances (10,12). At US, large hepatic abscesses have an appearance ranging from hypoechoic to hyperechoic, with varying degrees of internal echoes and debris (Fig 4). Gas in hepatic abscesses causes high-intensity linear echoes with acoustic shadowing or reverberation artifacts (13). At contrast-enhanced CT, large abscesses are generally well defined and hypoattenuating; they may be unilocular with smooth margins or complex with internal septa and an irregular contour (Fig 5). Rim enhancement is relatively uncommon, as is the presence of gas (10,12).
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Figure 3. Pyogenic microabscesses. Arterial phase contrast-enhanced CT scan shows multiple small hypoattenuating nodules representing pyogenic microabscesses scattered throughout the liver. Note the faint peripheral enhancement (arrow) and perilesional edema (arrowhead).
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Figure 4a. Pyogenic abscess. (a) Longitudinal US image demonstrates a pyogenic abscess with a typical hypoechoic appearance due to exudation and liquefaction necrosis (arrows). (b) Longitudinal US image obtained in a different patient shows a pyogenic abscess with the typical echogenic appearance caused by fibrotic changes (arrow).
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Figure 4b. Pyogenic abscess. (a) Longitudinal US image demonstrates a pyogenic abscess with a typical hypoechoic appearance due to exudation and liquefaction necrosis (arrows). (b) Longitudinal US image obtained in a different patient shows a pyogenic abscess with the typical echogenic appearance caused by fibrotic changes (arrow).
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Figure 5. Pyogenic abscess. Delayed-phase contrast-enhanced CT scan shows a large, hypoattenuating lesion in the right hepatic lobe with thin peripheral enhancement and surrounded by other smaller hypoattenuating areas (arrows). These smaller abscesses cluster or aggregate in a pattern that suggests coalescence into a single large cavity.
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At MR imaging, pyogenic abscesses have variable signal intensity on T1- and T2-weighted images, depending on their protein content. Perilesional edema, characterized by subtly increased signal intensity, can be seen on T2-weighted MR images.
Amebic Abscess
Entamoeba histolytica is endemic worldwide, with an estimated 10% of the world’s population being infected. It is most prevalent in India, Africa, the Far East, and Central and South America. Amebic liver abscess is the most common extraintestinal complication of amebiasis, occurring in 8.5% of cases. Hepatic infection occurs because colonic trophozoites ascend via the portal vein and invade the parenchyma (6,14).
Patients with amebic abscess are usually more acutely ill than patients with pyogenic abscess, with high fever and abdominal pain in the right upper quadrant; they are also younger and are usually from high-prevalence areas or recent travelers to such areas (15). Serum antibodies to Entamoeba species are present in more than 90% of cases (6). However, serologic findings may be negative in acute disease (but positive at repeat testing performed within 7–10 days) and may be positive if the patient had amebiasis in the past. Because amebicidal therapy is generally highly effective, catheter drainage of amebic abscess is rarely necessary (6,15).
Histologic features of amebic liver abscesses include scant inflammatory reaction at the margins and a shaggy fibrin lining. Because of hemorrhage into the cavities, the abscesses are sometimes filled with a chocolate-colored, pasty material known as "anchovy paste" (Fig 6). Secondary bacterial infection may make these abscesses purulent (14).
Both CT and US are sensitive in the detection of amebic abscesses. In many patients, it is difficult to differentiate amebic abscesses from pyogenic abscesses, but epidemiologic and clinical information, in conjunction with positive amebic titers, may suggest the diagnosis (1). At US, an amebic abscess may appear as a hypoechoic lesion with low-level internal echoes and absence of significant wall echoes. The lesion is typically oval or round and located near the liver capsule (16). At contrast-enhanced CT, amebic abscesses usually appear as rounded, well-defined lesions with attenuation values that indicate the presence of complex fluid (10–20 HU) (17). An enhancing wall 3–15 mm in thickness and a peripheral zone of edema around the abscess are common and somewhat characteristic for this lesion (Fig 7). The central abscess cavity may show multiple septa or fluid-debris levels and, rarely, air bubbles or hemorrhage (18). Extrahepatic extension of amebic abscess is relatively common, and involvement of the chest wall, pleural cavity, pericardium, and adjacent viscera has been reported.
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Figure 7a. Amebic abscess. (a) Contrast-enhanced CT scan demonstrates a large, lobulated, well-defined cystic mass in the right hepatic lobe. Note the enhanced, thickened wall of the lesion (arrows). (b) Contrast-enhanced CT scan obtained in a different patient shows a rounded, well-defined low-attenuation lesion in the right hepatic lobe with a small focus of air and mild hyperemia of the adjacent liver parenchyma.
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Figure 7b. Amebic abscess. (a) Contrast-enhanced CT scan demonstrates a large, lobulated, well-defined cystic mass in the right hepatic lobe. Note the enhanced, thickened wall of the lesion (arrows). (b) Contrast-enhanced CT scan obtained in a different patient shows a rounded, well-defined low-attenuation lesion in the right hepatic lobe with a small focus of air and mild hyperemia of the adjacent liver parenchyma.
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At MR imaging, amebic abscesses have homogeneous low signal intensity and high signal intensity on T1- and T2-weighted images, respectively. Perilesional edema is seen on T2-weighted MR images in 50% of cases (19).
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Parasitic Diseases
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E Granulosus (Hydatid) Cyst
Hydatid disease is a severe and common parasitic disease that is endemic to the Mediterranean basin and other sheep-raising areas (19). Humans become infected by ingestion of eggs of the tapeworm E granulosus, either by eating contaminated food or from contact with dogs. The ingested embryos invade the intestinal mucosal wall and proceed to the liver via the portal venous system. Although the liver filters out most of these embryos, those that are not destroyed become hepatic hydatid cysts. Biochemical analysis usually demonstrates eosinophilia, but a serologic test for the parasite is positive in only 25% of patients (1,19).
At histopathologic analysis, a hydatid cyst is composed of three layers: (a) the outer pericyst, which corresponds with compressed and fibrosed liver tissue; (b) the endocyst, an inner germinal layer; and (c) the ectocyst, a thin, translucent interleaved membrane (Fig 8). Maturation of a cyst is characterized by the development of daughter cysts in the periphery as a result of endocyst invagination (Fig 9). Peripheral calcifications are common in both viable and nonviable cysts (19).
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Figure 8. Hydatid disease. Photograph of a resected hydatid cyst shows the composition of the cyst wall: an outer pericyst (arrowheads), which corresponds to compressed liver tissue, and an endocyst (arrow), or inner germinal layer. The ectocyst, a thin, translucent interleaved membrane, is not seen.
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Figure 9a. Hydatid disease. (a) Photograph of a resected hydatid cyst reveals numerous daughter cysts. (b) Low-power photomicrograph (H-E stain) of a hepatic hydatid cyst in a different patient shows multiple daughter cysts and the matrix.
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Figure 9b. Hydatid disease. (a) Photograph of a resected hydatid cyst reveals numerous daughter cysts. (b) Low-power photomicrograph (H-E stain) of a hepatic hydatid cyst in a different patient shows multiple daughter cysts and the matrix.
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US findings are variable and range from purely cystic to solid-appearing pseudotumors (Fig 10) (18,20,21). Wavy bands of delaminated endocyst (water lily sign) may be noted internally (Fig 10c). Daughter cysts, sometimes surrounded by echogenic debris (matrix), are frequently seen. Calcifications, varying from tiny to massive, are often present peripherally (18,20,21).
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Figure 10a. Hydatid disease. (a) Longitudinal US image of the liver shows a rounded, well-defined, multilocular hypoechoic lesion with echogenic internal septa (arrows). (b) US image of the right hepatic lobe obtained in a different patient demonstrates a rounded hydatid lesion (cursors) with a global echogenic appearance. (c) US image of the liver obtained in a third patient shows a hydatid cyst in the right lobe with wavy bands of delaminated endocyst ("water lily sign") (arrows).
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Figure 10b. Hydatid disease. (a) Longitudinal US image of the liver shows a rounded, well-defined, multilocular hypoechoic lesion with echogenic internal septa (arrows). (b) US image of the right hepatic lobe obtained in a different patient demonstrates a rounded hydatid lesion (cursors) with a global echogenic appearance. (c) US image of the liver obtained in a third patient shows a hydatid cyst in the right lobe with wavy bands of delaminated endocyst ("water lily sign") (arrows).
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Figure 10c. Hydatid disease. (a) Longitudinal US image of the liver shows a rounded, well-defined, multilocular hypoechoic lesion with echogenic internal septa (arrows). (b) US image of the right hepatic lobe obtained in a different patient demonstrates a rounded hydatid lesion (cursors) with a global echogenic appearance. (c) US image of the liver obtained in a third patient shows a hydatid cyst in the right lobe with wavy bands of delaminated endocyst ("water lily sign") (arrows).
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At CT, a hydatid cyst usually appears as a well-defined, hypoattenuating lesion with a distinguishable wall (19). Coarse wall calcifications are present in 50% of cases, and daughter cysts are identified in approximately 75% (Fig 11) (19).
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Figure 11a. Hydatid disease. (a) Unenhanced CT scan of the liver shows a large, cystic mass with multiple septa. Note the presence of peripheral calcifications (arrows). (b) Unenhanced CT scan obtained in a different patient shows a large, multilocular hydatid cyst in the right hepatic lobe with multiple daughter cysts at the periphery. Note the hyperattenuating appearance of the matrix.
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Figure 11b. Hydatid disease. (a) Unenhanced CT scan of the liver shows a large, cystic mass with multiple septa. Note the presence of peripheral calcifications (arrows). (b) Unenhanced CT scan obtained in a different patient shows a large, multilocular hydatid cyst in the right hepatic lobe with multiple daughter cysts at the periphery. Note the hyperattenuating appearance of the matrix.
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Because of its superb contrast resolution, MR imaging best demonstrates the pericyst, the matrix or hydatid sand (debris consisting of freed scolices), and the daughter cysts (22). The pericyst is seen as a hypointense rim on both T1- and T2-weighted images because of its fibrous composition and the presence of calcifications. The hydatid matrix appears hypointense on T1-weighted images and markedly hyperintense on T2-weighted images; when present, daughter cysts are hypointense relative to the matrix on both T1- and T2-weighted images (Fig 12) (22).
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Figure 12a. Hydatid disease. (a) Axial gradient-echo T1-weighted MR image shows a hydatid cyst with a hypointense fibrous pericyst (arrow). The hydatid matrix has intermediate signal intensity, and peripheral daughter cysts that are hypointense relative to the matrix are seen. (b) On an axial T2-weighted MR image, the matrix is hyperintense and the daughter cysts again relatively hypointense.
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Figure 12b. Hydatid disease. (a) Axial gradient-echo T1-weighted MR image shows a hydatid cyst with a hypointense fibrous pericyst (arrow). The hydatid matrix has intermediate signal intensity, and peripheral daughter cysts that are hypointense relative to the matrix are seen. (b) On an axial T2-weighted MR image, the matrix is hyperintense and the daughter cysts again relatively hypointense.
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Although previously thought to be contraindicated, percutaneous drainage is gaining wider acceptance as a treatment for hydatid cysts. Generally, percutaneous treatment entails drainage and instillation of a sclerosing scolicidal agent after pretreatment with mebendazole. Complications include superinfection of the treated cavity and communication with the biliary tree (23,24).
E Multilocularis Cyst
E multilocularis is responsible for the rare multilocular or alveolar form of Echinococcus infection (25). It is endemic to much of the upper Midwest of the United States, Alaska, Canada, Japan, Central Europe, and parts of Russia. Definitive hosts are foxes and, less commonly, cats and dogs. Humans are infected either by direct contact with a definitive host or indirectly by ingestion of contaminated water or contaminated plants such as wild berries.
E multilocularis produces multilocular cysts that resemble alveoli and grow by exogenous proliferation. Small cysts less than 1 cm in diameter represent metacestodal vesicles, which are fluid-filled vesicles composed of an inner germinal layer, a syncytial tegument, and an outer acellular "laminated" layer. As they grow, these lesions show a strong tendency to develop central liquefactive necrosis, which may be surrounded by vital metacestodal vesicles (25). The liver is the most common site of E multilocularis infection, with over 90% of infected patients having liver involvement. The lesions may be single or multiple. Approximately 70% of these lesions develop in the right hepatic lobe.
At US, these lesions usually manifest with the "hailstorm" pattern, characterized by multiple echogenic nodules with irregular and indistinct margins (Fig 13) (26). Lesions with central liquefactive necrosis appear hypoechoic, with some internal echoes and an irregular hyperechoic border (26).
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Figure 13. E multilocularis cysts. Transverse US images obtained at different levels of the liver show E multilocularis infection with the typical hailstorm pattern, characterized by multiple echogenic nodules with irregular and indistinct margins.
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CT and MR images typically display multiple irregular, ill-defined lesions scattered throughout the involved liver that are generally hypoattenuating at CT (Fig 14) and hyperintense at T2-weighted MR imaging. This radiologic pattern may mimic either metastases or pyogenic abscesses. However, there is little or no enhancement after bolus administration of contrast medium, a finding that emphasizes the poor vascularization of the parasitic lesion. In advanced stages, irregular calcifications are found within the areas of central necrosis in 90% of infected patients. Hilar infiltration is observed in approximately 50% of patients and results in dilatation of the intrahepatic bile ducts and invasion of the portal and hepatic veins, with subsequent atrophy of the affected liver segments due to hypoperfusion (25).
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Figure 14a. E multilocularis. Unenhanced (a) and contrast-enhanced (b) CT scans of the liver reveal a large, irregularly shaped, hypoattenuating lesion with diffuse punctate calcifications, which are more clearly seen on the unenhanced image. Note the poor enhancement of the lesion after bolus administration of contrast material.
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Figure 14b. E multilocularis. Unenhanced (a) and contrast-enhanced (b) CT scans of the liver reveal a large, irregularly shaped, hypoattenuating lesion with diffuse punctate calcifications, which are more clearly seen on the unenhanced image. Note the poor enhancement of the lesion after bolus administration of contrast material.
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Schistosomiasis
Acute schistosomiasis remains a significant health risk for travelers to endemic regions (27). Schistosoma japonicum, S hematobium, and S mansoni are the three most important species that infect humans (28). The schistosomes live in the bowel lumen and lay eggs in the mesenteric veins. The eggs may then embolize to the portal vein, where they cause an inflammatory reaction with a granulomatous response, eventual fibrosis, and presinusoidal hypertension. The eggs themselves do not survive and may subsequently calcify. Chronic infections with either S japonicum or S mansoni result in the formation of cirrhosis and the risk of development of hepatocellular carcinoma (28).
The diagnosis is based on epidemiologic data, clinical manifestations, eosinophilia, the presence of living eggs at stool examination, or positive serologic findings for Schistosoma infection. At histologic analysis, mild hepatic schistosomiasis is characterized by white, pinhead-sized granulomas scattered throughout the liver. At the center of each granuloma is a schistosome egg (Fig 15). The granulomas are composed of macrophages, lymphocytes, neutrophils, and eosinophils. The liver is darkened by regurgitated heme-derived pigments from the schistosome gut. In severe infections, the surface of the liver shows granulomatous involvement and widespread fibrous portal enlargement ("pipe-stem" fibrosis) (14).
To our knowledge, imaging has made no significant contribution in the diagnosis of acute schistosomiasis due to S japonicum (27). Characteristic US and pathognomonic CT changes in the liver occur only many years after initial infection. Typical US findings include an irregular liver surface pattern and a mosaic pattern, with echogenic septa outlining polygonal areas of relatively normal liver parenchyma that vary in size from 15 to 30 mm (Fig 16). Less common and less specific US findings include a mottled, nodular or sieve-like appearance that represents partial septal fibrosis or calcifications, with concomitant hepatitis or cirrhosis (29,30).
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Figure 16. Schistosomiasis. Longitudinal US image through the liver shows the characteristic US network pattern, with echogenic septa (arrows) outlining polygonal areas of relatively normal liver parenchyma.
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At CT, the most pathognomonic pattern is the presence of calcified septa, usually aligned perpendicular to the liver capsule ("tortoise shell" or "turtle back" appearance) (Fig 17). Other recognized CT features include capsular calcification, junctional notches or depressions, an irregular hepatic contour, and extension of periportal fat deep into the liver as a result of fibrosis and parenchymal retraction. MR imaging cannot accurately depict these characteristic calcifications. However, the fibrous septa have abnormal decreased and increased signal intensity on T1- and T2-weighted images, respectively (31).
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Figure 17. Schistosomiasis. CT scan of the liver reveals characteristic pericapsular and periportal calcifications, which give the liver a tortoise shell appearance. The calcifications form as a result of embolization of the schistosome eggs to these areas in the liver, with ensuing inflammatory reaction and fibrosis.
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US findings that characterize chronic schistosomiasis due to S mansoni consist of wall thickening of the portal veins and its branches, associated with increased echogenicity. This typical "bull’s-eye" appearance represents an anechoic portal vein surrounded by an echogenic mantle of fibrous tissue. Other findings are a hypertrophic left hepatic lobe, splenomegaly, and the presence of collateral vessels (30). At CT, the periportal fibrosis manifests as low-attenuation rings around the portal vein branches throughout the liver, with marked enhancement following intravenous administration of contrast material. At MR imaging, the periportal bands are isointense relative to normal liver parenchyma on T1-weighted images and hyperintense on T2-weighted images, with marked enhancement following contrast material administration (30,31).
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Fungal Diseases
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Hepatosplenic fungal infection is a clinical manifestation of disseminated fungal disease in patients with hematologic malignancies or compromise of the immunologic system. The reported prevalence of fungal dissemination in affected patients ranges from 20% to 40%. Microabscesses often also involve the spleen and, occasionally, the kidney. Most hepatic fungal microabscesses occur in leukemia patients and are caused by Candida albicans; other fungus-related diseases include Cryptococcus infection, histoplasmosis, and mucormycosis. Sporadic cases of liver infection by Aspergillus species have also been reported (6).
Candidiasis
Histologic analysis shows that Candida species may evoke little or no inflammatory reaction, may cause the usual suppurative response, or may occasionally produce granulomas in the liver (Fig 18). The typical histologic pattern of hepatic candidiasis is characterized by microabscesses, with the yeast or pseudohyphal forms of the fungus in the center of the lesion and a surrounding area of necrosis and polymorphonuclear infiltrate; in the healing stage, the microabscesses may be smaller and the amount of fibrous tissue increased (14).
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Figure 18a. Candidiasis. (a) Photograph of a gross specimen of the spleen shows multiple small, white nodules representing involvement by candidiasis throughout the parenchyma. (b) Low-power photomicrograph shows multiple candidiasis microabscesses with a peripheral zone of fibrosis and a central area of necrosis (arrows).
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Figure 18b. Candidiasis. (a) Photograph of a gross specimen of the spleen shows multiple small, white nodules representing involvement by candidiasis throughout the parenchyma. (b) Low-power photomicrograph shows multiple candidiasis microabscesses with a peripheral zone of fibrosis and a central area of necrosis (arrows).
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CT and US findings correlated with clinical findings are sensitive in the diagnosis of fungal microabscesses greater than 1 cm. Four US patterns of hepatosplenic candidiasis have been described (32). The first pattern, described as having a "wheel-within-a-wheel" appearance, consists of a central hypoechoic area of necrosis containing fungi and surrounded by an echogenic zone of inflammatory cells. A hypoechoic rim is noted at the periphery, corresponding to fibrosis at pathologic analysis. The second pattern is a bull’s-eye configuration consisting of a central echogenic nidus surrounded by a hypoechoic rim. In general, this second pattern occurs in patients with active fungal infection and a relatively normal white blood cell count (32). The third pattern consists of a uniformly hypoechoic nodule and is the most common pattern at US; however, it is the least specific appearance of candidiasis and may simulate metastatic disease or lymphoma. The fourth pattern consists of echogenic foci with variable degrees of posterior acoustic shadowing. This pattern occurs in later stages of infection and generally indicates early resolution (32).
At contrast-enhanced CT, fungal microabscesses usually appear as multiple round, discrete areas of low attenuation, generally ranging from 2 to 20 mm (Fig 19). These microabscesses usually enhance centrally after intravenous administration of contrast medium, although peripheral enhancement may occur (33–35).
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Figure 19. Candidiasis. Contrast-enhanced CT scan of the liver shows multiple hypoattenuating microabscesses less than 1 cm in diameter disseminated throughout the hepatic parenchyma.
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At MR imaging, the untreated nodules are rounded lesions less than 1 cm in diameter that are minimally hypointense on T1-weighted and gadolinium-enhanced images and markedly hyperintense on T2-weighted images (36,37). In the subacute presentation after treatment, lesions appear mildly to moderately hyperintense on T1- and T2-weighted images and demonstrate enhancement on gadolinium-enhanced images (Fig 20) (36). A dark ring is usually seen around these lesions with all sequences. Completely treated lesions are minimally hypointense on T1-weighted images, isointense to mildly hyperintense on T2-weighted images, moderately hypointense on early gadolinium-enhanced images, and minimally hypointense on delayed gadolinium-enhanced images (38). Several authors have suggested that MR imaging is superior to CT and US in the detection of these fungal foci (37,38).
Other Fungal Diseases
Other fungal organisms that less commonly infect immunocompromised patients include Aspergillus species, C neoformans, Histoplasma capsulatum, Trichosporum begellii, and Coccidioides immitis. The imaging features of all types of fungal diseases are similar.
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Granulomatous Diseases
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Granulomatous hepatitis is defined as an inflammatory liver disease associated with granuloma formation in the liver. Granulomatous hepatitis is associated with a wide variety of conditions, most commonly with sarcoidosis, tuberculosis, and histoplasmosis (39). Diagnosis of granulomatous hepatitis is based solely on a finding of granulomas in the liver tissue. Hepatic granulomas usually appear as discrete, sharply defined nodular infiltrates consisting of aggregates of epithelioid cells or macrophages surrounded by a rim of mononuclear cells, predominantly lymphocytes. In tuberculosis, the granulomas may undergo central liquefaction necrosis, and reticulin forms around the granuloma, which eventually undergoes fibrosis (39).
Tuberculosis
Tuberculosis is one of the most common infectious diseases, with a worldwide distribution and a variety of clinical manifestations. Tuberculosis is known to involve the liver in different ways. Generally, tuberculosis of the liver is classified as either a miliary form, which is part of generalized miliary tuberculosis, or a local form, which is further subdivided into focal or nodular tuberculosis (ie, tuberculous hepatic abscess and tuberculoma) and tubular or hepatobiliary tuberculosis (ie, tuberculosis involving the intrahepatic ducts) (40). Miliary tuberculosis of the liver is most common and is reported to occur in 50%–80% of all patients with terminal pulmonary tuberculosis.
Miliary tuberculosis is usually not detected at imaging, and hepatomegaly may be the only radiologic abnormality. In the healing stage of tuberculosis, CT may show diffuse hepatic calcifications (approximately 50% of cases). At US, detectable tuberculomas usually manifest as round, hypoechoic masses, although hyperechogenic lesions have also been described (40–42). Reported CT findings are nonspecific and include the presence of hypoattenuating lesions both before and after intravenous administration of contrast material (Fig 21). At MR imaging, the lesions are hypointense on T1-weighted images and hypo- to isointense on T2-weighted images (43).
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Figure 21. Tuberculosis. Contrast-enhanced CT scan demonstrates multiple low-attenuation areas of varying size in the liver and spleen. The imaging findings in hepatic tuberculosis are nonspecific; therefore, biopsy is mandatory in almost all cases in which this disease is suspected.
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Because of these rather nonspecific findings with all imaging techniques, percutaneous liver biopsy is necessary in almost all patients with liver lesions that are suspicious for tuberculosis. Diagnosis can be established by showing caseating granuloma, a positive acid-fast bacillus or culture for Mycobacterium species, or a positive polymerase chain reaction (43).
Histoplasmosis
Histoplasmosis is the most common cause of fungal infection in the Ohio River Valley of the United States. Fortunately, 99% of patients exposed to histoplasmosis develop only subclinical infections. Liver involvement is common in disseminated histoplasmosis, which usually originates in the lungs. The most common hepatic findings include portal lymphohistiocytotic inflammation and discrete, well-formed granulomas, the latter being seen in approximately 20% of involved livers. In the acute setting, hepatic imaging findings include hepatomegaly and hypoattenuating lymph nodes. In patients with healed histoplasmosis, the presence of small, punctate calcifications scattered throughout the liver and spleen is a typical but nonspecific finding.
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Viral Hepatitis
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Acute viral hepatitis is a systemic infection that affects the liver and is usually caused by one of five viral agents: hepatitis A virus, hepatitis B virus (HBV), hepatitis C virus, the HBV-associated delta agent or hepatitis D virus, and hepatitis E virus. A vast array of other viruses may also produce hepatitis, including herpes viruses, yellow fever virus, rubella virus, Coxsackie virus, and adenovirus. Although these viruses can be distinguished by their molecular and antigenic properties, all types of viral hepatitis produce clinically similar illnesses. These illnesses range from asymptomatic, inapparent infections to fulminant, fatal acute infections (common to all types of viruses), and from subclinical persistent infections to rapidly progressive chronic liver disease with cirrhosis (common to the blood-borne types [HBV and hepatitis C or D virus]) (41).
In chronic hepatitis, the hepatic inflammation and necrosis continue for at least 6 months. Complications that occur during end-stage chronic hepatitis include ascites, edema, variceal bleeding, hepatic encephalopathy, coagulopathy, hypersplenism, and development of hepatocellular carcinoma.
In acute viral hepatitis, the major histologic findings are (a) necrosis of random isolated liver cells or small cell clusters, (b) diffuse liver cell injury, (c) reactive changes in Kupffer cells and sinusoidal lining cells and an inflammatory infiltrate in portal tracts, and (d) evidence of hepatocytic regeneration during the recovery phase. Confluent necrosis may lead to bridging necrosis connecting portal, central, or portal-to-central regions of adjacent lobules, signifying a more severe form of acute hepatitis (14).
The morphologic features of chronic hepatitis are variable. In the mildest form, an inflammatory infiltrate is limited to portal tracts. The histologic hallmark of progressive disease is piecemeal necrosis, whereby chronic inflammatory cells extend out from portal tracts into adjacent parenchyma, with associated necrosis of hepatocytes in the limiting plate. Continued loss of hepatocytes resulting in fibrous septum formation accompanied by hepatocyte regeneration determines progression of disease to cirrhosis (14).
The imaging features of acute hepatitis are nonspecific, and the diagnosis is usually based on serologic, virologic, and clinical findings. Probably the most important role of radiology in patients with suspected hepatitis is to help rule out other diseases that produce similar clinical and biochemical abnormalities, such as extrahepatic cholestasis, diffuse metastatic disease, and cirrhosis (28).
At US, in acute hepatitis, the liver is often enlarged and may demonstrate a diffuse decrease in parenchymal echogenicity, which causes a relative increase in the echogenicity of the portal vein walls ("starry night" pattern) (28). A normal liver echotexture does not exclude the diagnosis of acute hepatitis. At CT and MR imaging, findings in acute viral hepatitis are nonspecific and include hepatomegaly and periportal edema (Fig 22) (44,45). At CT, heterogeneous enhancement and well-defined regions of low attenuation may be present (46). At MR imaging, periportal edema appears as high-signal-intensity areas on T2-weighted images. Involved areas may be normal or demonstrate decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images (47). Extrahepatic findings in patients with severe acute hepatitis include gallbladder wall thickening due to edema and, infrequently, ascites.
Although chronic hepatitis displays normal US findings in many cases, it can manifest with a coarsened hepatic echotexture and increased parenchymal echogenicity, causing portal vein radicles to be less conspicuous. The appearance of the liver is essentially identical to that seen with diffuse fatty change (45). In patients with chronic hepatitis, the CT and MR imaging features resemble those of early-stage liver cirrhosis. Periportal lymphadenopathy may be the sole detectable abnormality in both acute and chronic hepatitis (28).
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Uncommon Hepatic Infections
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Bacillary Angiomatosis
Bacillary angiomatosis is a manifestation of infection by Bartonella henselae in immunocompromised patients. This is the same organism that causes cat-scratch disease in noncompromised patients. It is characterized by localized areas of vascular proliferation that may affect the skin, airway, mucous membranes, visceral organs, bone, and brain (48–50). Peliosis hepatis is the term used for liver infection by B henselae. This condition occurs almost exclusively in patients with acquired immunodeficiency syndrome (AIDS). The mechanism of transmission is unknown, but involvement by animal or insect vectors has been postulated (48–50).
At histologic analysis, a typical specimen exhibits several well-formed capillaries surrounded by granular extracellular material and neutrophils. This granular material is composed of clumps of pleomorphic, curved rods of B henselae and is characteristically Warthin-Starry stain positive (48–50).
US may show multiple small, round hypoechoic lesions, usually involving both the liver and spleen (51,52). Contrast-enhanced CT may demonstrate multiple diffuse low- or high-attenuation lesions less than 1 cm scattered throughout the hepatic parenchyma (Fig 23). Ascites, mild periportal edema, and intrahepatic biliary ductal dilatation may occur. These imaging features are nonspecific and must be distinguished, especially in AIDS patients, from hepatic abscesses related to other bacteria, viruses, or fungi; AIDS-related lymphoma; Kaposi sarcoma; and, less commonly, disseminated Pneumocystis carinii infection (52).
HIV Infection
The liver and biliary tracts are frequent sites of involvement during the course of HIV infection (53). A variety of viral, bacterial, fungal, and other opportunistic infections can manifest with hepatobiliary involvement as either the primary site of infection or secondary to a disseminated process. Coinfection with hepatitis B and C viruses is particularly common due to the shared means of transmission of these viruses with HIV (53). AIDS-related cholangiopathy has also been described, and four different patterns have been reported: (a) papillary stenosis with dilatation of the bile ducts and delayed drainage, (b) sclerosing cholangitis characterized by focal strictures and dilatation of the intra- or extrahepatic bile ducts, (c) combined papillary stenosis and intra- or extrahepatic sclerosing cholangitis, and (d) long extrahepatic bile duct strictures. Biliary tract infections by several organisms have been implicated in the development of AIDS-related cholangitis but not directly demonstrated as causative. Direct involvement by HIV has also been postulated as a possible cause (54).
US, CT, and endoscopic retrograde cholangiopancreatography are complementary in the diagnosis of AIDS-related cholangiopathy. US findings include dilatation and mural thickening of the gallbladder and common bile duct as well as pericholecystic fluid. Dilated intrahepatic ducts, gallbladder dilatation, and sludge are also commonly found. At CT, inflammation of the gallbladder or biliary tree manifests as mural thickening or abnormal contrast enhancement. Cholangiography is more
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Abstract
LEARNING OBJECTIVES FOR TEST...
