Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

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Figure 7.14. Primary biliary cirrhosis. Only limited intrahepatic bile ducts are filled in spite of a vigorous contrast injection.

of cirrhosis, except for a higher prevalence of diffuse liver enlargement.

A MR periportal halo sign is helpful in identifying this entity (Fig. 7.15). This sign, consisting of a hypointense focus centered around a portal vein branch and identified either on T1or T2-weighted images, was found in 43% of patients with primary biliary cirrhosis awaiting transplantation but in no other cirrhotic patients (48).

Figure 7.15. Primary biliary cirrhosis. Transverse T1-weighted MRI reveals round, hypointense lesions surrounding portal veins (arrows), a finding termed the periportal halo sign. (Courtesy of Jeffrey Wenzel, M.D., Southwest Imaging, Dallas, Texas.)

Computed tomography identifies lymphadenopathy in about 90% of patients with primary biliary cirrhosis requiring orthotopic liver transplantation (49). Adenopathy usually involves periportal and hepatoduodenal ligament nodes, and such adenopathy must be differentiated from that seen with neoplasms. A rough correlation exists between the size of the hepatoduodenal ligament lymph nodes and the degree of hepatocellular damage.

Therapy

The most common causes of death in patients with primary biliary cirrhosis are hepatic failure and gastrointestinal bleeding from varices. Currently no definitive therapy is available aside from liver transplantation. Transplantation has had a significant impact on patient survival. Nevertheless,the histologic features suggestive of recurrence develop in some transplant patients, with the recurrence rate apparently influenced by the type of immunosuppression used. During follow-up after orthotopic liver transplantation, 4% of patients developed recurrence (49).

Secondary Biliary Cirrhosis

Chronic biliary obstruction does evolve into cirrhosis. The overall appearance is similar to that seen in primary biliary cirrhosis, except for increased bile stasis and a lack of duct degeneration.

Liver involvement is uncommon in children with cystic fibrosis, but increasing survival of these patients has led to an increased number presenting with liver disease. These older children and young adults develop focal biliary cirrhosis, which eventually evolves into portal hypertension (Fig. 7.16). Some cystic fibrosis patients have undergone liver transplantation. Whether screening is useful in cystic fibrosis patients with chronic liver disease prior to developing cirrhosis remains to be established.

Fibrosis

Fibrosis is a response to a number of chronic liver insults. In some disorders fibrosis predominates with few or no parenchymal abnormalities identified.

Figure 7.16. A cirrhotic liver in a 24-year-old man with cystic fibrosis and hepatic failure. The liver has a nodular outline. Splenomegaly and vascular congestion (arrowheads) are secondary to portal hypertension. (Courtesy of Douglas S. Katz, M.D., Winthrop University Hospital, Mineola, New York.)

Ultrasonography typically reveals a hyperechoic pattern throughout a fibrotic liver. The hyperechoic changes with periportal fibrosis are seen mostly around the portal vein branches, separated from the adjacent liver parenchyma by a hypoechoic region. The underlying portal vein branches tend to be deformed.

The MRI changes of fibrosis are rather characteristic and familiar to most radiologists. SPIO-enhanced MR imaging identifies fibrosis by decreasing signal intensity from nonfibrotic regions containing Kupffer cells (50). Problems exist when fibrosis is only one part of a complex entity.

Vanishing Bile Duct Syndrome

An occasional patient with cholestasis has narrowed or small intrahepatic bile ducts (ductopenia) with no underlying disease being identified. This condition, termed vanishing bile duct syndrome, probably represents an immunologic or hypersensitive hepatotoxic reaction. Numerous drugs are associated with this condition. Pathologically, it should be suspected if absent interlobar bile ducts are found in over 50% of portal triads. Progressive cholestasis and loss of intrahepatic bile ducts in some of these patients develop to the point that a liver transplant is necessary.

Superficially, the imaging appearance of vanishing bile duct syndrome resembles diffuse intrahepatic sclerosing cholangitis.

Progressive cholestasis and the loss of intrahepatic bile ducts in some of these patients develop to the point that a liver transplant is necessary.

Iron Overload

Clinical

As a rough guide, a normal adult body contains about 4 to 5g of iron, of which 80% is in hemoglobin, myoglobin, and iron-containing enzymes and 1g of iron is stored. Ingested and absorbed iron is bound to transferrin and deposited in bone marrow, hepatocytes, muscle, and other tissues, but not reticuloendothelial cells; the latter derive their iron mostly from phagocytosed red blood cells. Of importance from an imaging viewpoint is that disorders associated with too much ingested iron then store the excess iron in the liver (hepatocytes) and pancreas, while iron from excess blood transfusions is stored in the liver (reticuloendothelial cells), spleen, and bone marrow. Disorders associated with excess hemolysis also lead to renal iron accumulation. Hemorrhage into tissues results in focal iron accumulation.

Iron is a hepatotoxin. Excess iron deposition in body tissues without organ damage is known as hemosiderosis. Hemochromatosis is an ironoverload disorder with structural and functional impairment of involved organs. Primary (hereditary or genetic) hemochromatosis is an inherited abnormality characterized by increased iron absorption from the gastrointestinal tract and resultant tissue iron overload. It is the most common inherited single gene disorder in those of northern European descent (51). Two point mutations in the hemochromatosis candidate gene HFE are known as C282Y and H63D. A diagnostic genotypic test for the C282Y mutation is available. Although this genetic test identifies most hemochromatosis patients, both iron-overload patients without this mutation and homozygous patients without iron overload also exist. In some patients both genetic and acquired factors play a role.

During the early latent stage of compensated hereditary hemochromatosis, aside from iron overload, only minimal hepatocyte damage is evident, but iron overload beyond a critical level

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results in hepatocytic and sinusoidal cell siderosis and intracellular damage and necrosis.

Classic findings of hereditary hemochromatosis consist of bronze diabetes and an underlying cirrhosis, although currently a diagnosis is more often made at an earlier stage. Ideally, the quantity of liver iron overload is determined from a liver biopsy, but the diagnosis is often based mostly on an elevated fasting transferrin saturation level.

Hepatic iron deposition is common in thalassemia and chronic hepatitis, making differentiation between chronic hepatitis and hereditary hemochromatosis difficult. At times these disorders coexist; thus hepatitis C and hereditary hemochromatosis have led to endstage liver disease in children. Secondary hemochromatosis develops most often in patients requiring long-term blood transfusions and those ingesting large amounts of iron. Multiple transfusions eventually lead to extensive iron overload in reticuloendothelial cells, and liver fibrosis is not a prominent feature. Bantu siderosis patients ingest large amounts of iron, which is stored mostly in reticuloendothelial cells and, to some degree, in hepatocytes.

Thalassemia patients also have increased oral iron absorption, driven not by genetic factors directly as in hereditary hemochromatosis but by increased erythroid hyperplasia. These patients initially develop liver findings similar to hereditary hemochromatosis, but additional iron overload due to transfusions modifies this appearance.

Sideroblastic anemia and erythropoiesis also result in secondary hemochromatosis, somewhat similar to transfusion overload. Hemosiderin accumulates in sideroblasts and hepatocytes, but not splenic reticuloendothelial cells. As a result, these patients have a hypointense liver and bone marrow but a close to normal appearing spleen on T1-weighted MR images. Nevertheless, some of these patients receive blood transfusions and the MR appearance can be confusing.

Untreated, patients with hereditary hemochromatosis progress to cirrhosis, congestive heart failure, and various endocrine abnormalities, including diabetes mellitus. Disease progression is gradual,findings are nonspecific,and the true cause is thus often overlooked, especially during the early phase. These patients are at increased risk of developing a hepatocellular

carcinoma. A rare cholangiocarcinoma has developed in hemochromatosis, but whether this is fortuitous or not is speculation.

Imaging

A linear relationship exists between CT attenuation and liver iron content. Computed tomography sensitivity is improved by using 80kVp instead of the usually used 120kVp. Nevertheless, CT sensitivity in measuring liver iron is rather low, and most current research is centered on MR. When hemochromatosis is well established, the intrahepatic vessels are at a lower density than liver parenchyma; this finding is not pathognomonic, and high parenchymal attenuation is found in patients being treated with drugs such as amiodarone (amiodarone and its metabolites contain iodine and are concentrated in hepatocytes), gold therapy,prior thorium dioxide (Thorotrast) use, and occasionally in Wilson’s disease.

Liver US is normal in most patients with early hemochromatosis.

Being a paramagnetic substance, iron becomes magnetized within a magnetic field, adjacent water photons lose phase coherence, and the overall effect is a hypointense MR signal. Magnetic resonance imaging in hereditary hemochromatosis reveals a decrease in liver and pancreas signal intensity on T2weighted sequences. No such decrease in signal intensity is found in the spleen because no significant iron is deposited in the reticuloendothelial system. In iron overload due to transfusion, on the other hand, iron is deposited mostly in the reticuloendothelial cells of the spleen and liver, with relative sparing of liver hepatocytes and pancreas; as a result, a decreased signal intensity is evident on T2weighted images of both the liver and spleen (Fig. 7.17). Initially in iron overload, signal intensity on T1-weighted images is normal but with more severe involvement a hypointense signal also becomes evident. An inverse linear relationship exists between iron concentration and signal intensity liver-to-muscle ratio. Overall, MRI detects relatively low levels of iron overload. A mathematic model is available to estimate iron concentrations from MR imaging data (52), but stringent calibration is required. Among other variables, MR field strength influences the effect of liver iron. A correlation

Figure 7.17. Iron overload in a 10-year-old with sickle cell disease and multiple transfusions. MR shows a markedly hypointense liver and spleen. (Source: Burgener FA, Meyers SP, Tan RK, Zaunbauer W. Differential Diagnosis in Magnetic Resonance Imaging. Stuttgart: Thieme, 2002, with permission.)

Liver iron deposition introduces MR interpretation problems when imaging other diseases, because iron reduces parenchymal signal intensity, and some malignant foci appear more bright than usual and tend to simulate benign lesions. The reverse is also true with inflammatory conditions that increase parenchymal signal intensity.

Therapy

Hereditary hemochromatosis is often not considered in patients with end-stage liver disease because elevated iron levels are common in many other diseases. In fact, at times hemochromatosis is not even diagnosed prior to transplantation. An incidental hepatocellular carcinoma is not an uncommon finding at the time of transplantation.

These patients appear to have a higher posttransplantation mortality than patients transplanted for other causes. Also, they have increased infectious and cardiac complications.

exists between iron concentrations obtained from percutaneous needle biopsies and a ratio of signal intensity of the liver to background noise obtained from MR sequences. Skeletal muscle T2 values are relatively constant over a wide range of iron stores and can thus be used as a reference standard. The liver-to-muscle proton density ratio correlates with hepatic iron, yet the low signal-to-noise ratios seen with high iron levels are difficult to quantitate. Although in practice MRI appears sufficiently accurate to measure liver iron concentrations, in general, qualitative results aid in establishing a diagnosis but quantitative correlation is imprecise.

Thalassemic patients without blood transfusions have an MR appearance similar to those with hereditary hemochromatosis, but after blood transfusions the picture alters, with excess iron in organs rich in reticuloendothelial cells. A multicenter MR study of thalassemia major patients suggests that the signal intensity ratio of liver-to-muscle is related to liver iron concentration (53). Hepatic 1/T2 values correlate with liver iron concentration. In general, a close correlation exists between biopsy liver iron levels and MR signal intensity.

Silicosis

Hepatosplenic silicosis also develops in patients with pulmonary silicosis. Liver biopsy in these patients reveals birefringent crystals in hyalinized nodules.

Calcified splenic nodules are detected with conventional radiography, CT, or US. Faint intrahepatic calcifications or “egg-shell” lymph node calcifications are best evaluated by CT.

Amyloidosis

Amyloidosis can be primary, secondary, or familial. In primary systemic amyloidosis, amyloid is deposited in the liver, spleen, and other structures; at times primarily liver deposits occur. A rare patient progresses to cholestasis, severe jaundice, and hepatic failure. Sinusoidal portal hypertension and spontaneous liver rupture are rare complications of primary amyloidosis.

Liver enlargement is a prominent feature in some patients. The liver is diffusely involved in both primary and secondary amyloidosis, but at times involvement is nonuniform. Hepatic and splenic calcifications are rare in primary amyloidosis. When amyloidosis is well established, noncontrast CT reveals decreased liver

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parenchymal attenuation. Heterogeneous enhancement is evident postcontrast. Ultrasonography reveals a heterogeneous echo pattern.

Liver transplantation is the only effective treatment of familial amyloidosis; patients in a good nutritional state have a significantly better survival rate.

Sarcoidosis

Sarcoidosis, a granulomatous disorder of unknown etiology, is commonly diagnosed on clinical and imaging ground. The previously used Kveim test is considered too nonspecific. The angiotensin-converting enzyme (ACE) level correlates with disease activity. The lungs are primarily involved; in the abdomen, liver, spleen, and lymph nodes are most often involved, although hepatic sarcoidosis is usually asymptomatic and cholestasis infrequent.

Biopsy reveals noncaseating epithelial granulomas, often when liver function tests are still normal, but other causes of liver granulomas need be excluded, including a secondary sarcoid reaction to a neoplasm. At times histologic differentiation from sclerosing cholangitis is difficult.

Occasionally hepatic sarcoidosis progresses to cirrhosis and portal hypertension. Resultant esophageal variceal bleeding that some of these patients develop is amenable to sclerotherapy, although occasionally a shunt is necessary.

The most common CT findings of abdominal sarcoidosis are hepatosplenomegaly and diffuse adenopathy. In a minority of patients multiple hypodense nodules secondary to coalescing granulomas are found in the liver and spleen; these nodules are better identified on contrast CT. Periportal adenopathy is common and at times sufficiently extensive to result in obstructive jaundice.

Sarcoid nodules are hypointense both on T1and T2-weighted images. They show mild, delayed contrast enhancement. The surrounding vasculature tends to be normal, thus differentiating these nodules from a malignancy. Nevertheless, the overall imaging appearance often suggests metastases, lymphoma, or even hepatic tuberculosis, especially in the uncommon patient with a normal chest radiograph.

Reticuloendothelial Failure

Hepatic reticuloendothelial failure is a poorly understood condition associated with decreased Kupffer cell function. It tends to be underdiagnosed. These patients are prone to develop infections.

Radiocolloid Tc-99m-phytate scintigraphy suggests the diagnosis; the liver is not visualized with this radiocolloid agent, but is imaged with conventional hepatobiliary agents such as Tc- 99m-DTPA.

Liver in Pregnancy

Middle hepatic vein Doppler US waveform early in pregnancy has normal pulsatility, but with progression of pregnancy hepatic vein pulsatility becomes more and more flat.

Acute fatty liver occurs during pregnancy, occasionally even as early as 26 weeks, can progress to acute hepatic failure. Any transaminase elevation during pregnancy should be viewed with suspicion. A high fetal death rate is associated with acute fatty liver, but some pregnancies are managed successfully; following delivery liver function returns to normal, with only an occasionally preeclampsia persisting postpartum, liver enzymes remaining elevated, and hemolytic-uremic syndrome developing. Liver rupture is a rare complication of severe preeclampsia.

A rare complication of preeclampsia is the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). It occurs during both pregnancy and the puerperium. Gross liver involvement ranges from subcapsular hematoma, to infarction, to small vessel occlusion, to spontaneous liver rupture.

Upper abdominal pain, nausea, and vomiting, by themselves nonspecific findings in pregnancy, are common in the HELLP syndrome. Initial clinical findings tend to suggest gallbladder disease, and US is often first performed. Although US will detect a hematoma, CT not only identifies hematomas but should also detect liver infarction or rupture, and identify any active bleeding site. Once HELLP is established, thrombocytopenia and fibrinolysis become evident and suggest the diagnosis. Liver MR spectroscopy of seven women with HELLP syndrome found relative hepatic concentrations

of phosphorus-containing metabolites and absolute concentrations of adenosine triphosphate to be similar to controls, but severe involvement results in a relative increase in phosphomonoester and an absolute decrease in hepatic adenosine triphosphate (54).

Several intrahepatic pregnancies have been described. At times CT and US identify a living fetus. Massive hemorrhage and hypovolemic shock are not uncommon presentations during the first trimester.

Tumors

A list of focal liver tumors is legion. Even such entities as focal fat and focal sparing, generally not considered as tumors, are in the imaging differential diagnosis. The simplest classification of primarily hepatocellular-origin tumors is to subdivide them into regenerative nodules (solitary necrotic nodule, focal nodular hyperplasia, nodular regenerative hyperplasia, and regenerative nodule of cirrhosis) versus dysplastic-neoplastic nodules (dysplastic nodule, adenoma, and hepatocellular carcinoma). Benign liver tumors can be divided into

ADVANCED IMAGING OF THE ABDOMEN

nonneoplastic and neoplastic (Table 7.8). With some neoplastic tumors the boundary between benign and malignant is blurred to the point that even a pathologist is hard-pressed to differentiate them. Some of the tumors developing in infants and children are unique to the pediatric patient, while others are similar to those seen in adults (Table 7.9). The most common liver malignancy in children under 3 years of age is a hepatoblastoma, while in older children a hepatocellular carcinoma is more common.

Discussion of hepatobiliary tumors is divided between this chapter and Chapter 8, but such a distinction is arbitrary. Those tumors manifesting primarily by bile duct involvement, both intrahepatic and extrahepatic, are discussed in Chapter 8. The outline adopted here is based on a broad pathologic classification modified by imaging findings. Most specialists would subdivide liver tumors based on their own viewpoint.

Detection of Focal Tumors

From an imaging viewpoint, a useful differentiation is between hypervascular and hypovascu-